Nutritional practices of elite female surfers during training and competition

Inhaled beryllium (Be) can induce a range of adverse pulmonary responses in animals and humans including acute pneumonitis, chronic granulomatous lung disease, and cancer. To facilitate comparisons with our previous data describing Be toxicity in rats, we evaluated the toxic effects of inhaled Be metal in mice. Groups of 34 strain C3H/HeJ mice were acutely exposed by the nose-only route to aerosolized Be metal to achieve measured initial lung burdens of 0, 1.7, 2.6, 12, or 34 microg. All mice received aerosolized 85 Sr-labeled fused aluminosilicate particles (85 Sr-FAPs) immediately before their Be exposure so that the influence of Be on lung retention of these poorly soluble tracer particles could be externally quantitated. Groups of mice were euthanized at 8, 15, 40, 90, 210, and 350 days after exposure for evaluation of histopathological changes and for cytologic and biochemical indicators of lung damage measured in bronchoalveolar lavage fluid. Clearance of 85 Sr-FAP tracer particles through 196 days after exposure was delayed in mice receiving the 12 and 34 microg Be lung burdens, but not the 1.7 or 2.6 microg lung burdens. Increased total cell numbers, increased percentage of neutrophils, and elevated levels of total protein and the activities of beta-glucuronidase and lactate dehydrogenase in bronchoalveolar lavage fluid were observed in the two highest Be lung burden groups compared with controls. Lung lesions included particle-containing macrophages, granulomatous pneumonia, lymphocytic interstitial aggregates, and mononuclear interstitial infiltrates. These lesions were occasionally seen in mice receiving the 2.6 microg lung burden, were present in most of the mice receiving 12 or 34 microg lung burdens, and were generally increased in severity with time and lung burden. Thus, we have demonstrated that a single, acute inhalation exposure to Be metal can chronically retard particle clearance and induce lung damage in mice. The initial lung burdens used caused responses ranging from no apparent effects to significant Be-induced responses. A comparison of these data with our previous data from rats indicates that the mass of Be metal required to induce lung damage in mice is similar to that needed for rats. When expressed on a lung weight-normalized basis, mice appeared to be more resistant to the toxic effects of inhaled Be than rats.     

Toxicokinetics of inhaled 2-butoxyethanol and its major metabolite, 2-butoxyacetic acid, in F344 rats and B6C3F1 mice

2-Butoxyethanol (2BE) is used extensively in the production of cleaning agents and solvents. It is primarily metabolized in the liver to 2-butoxyacetic acid (2BAA), which is believed to be responsible for 2BE toxicities associated with hemolysis of red blood cells. The objective of the study was to characterize the systemic disposition of 2BE and 2BAA in rats and mice during 2-year 2BE inhalation toxicity studies. Male and female F344 rats and B6C3F1 mice (6-7 weeks old) were exposed to target 2BE concentrations of 0, 31.2, 62.5, or 125 ppm (rats), or 0, 62.5, 125, or 250 ppm (mice), by whole-body inhalation for 6 h/day, 5 days/week for up to 18 months. Postexposure blood samples were collected after 1 day, 2 weeks, and 3, 6, 12, and 18 months of exposure. Postexposure 16-h urine samples were collected after 2 weeks and 3, 6, 12, and 18 months of exposure. A separate set of mice was kept in the control chamber and exposed to 2BE for 3 weeks when they were approximately 19 months old. Postexposure blood samples were collected after 1 day and 3 weeks of exposure and 16-h urine samples were collected after 2 weeks of exposure from these aged mice. Blood samples were analyzed for both 2BE and 2BAA and urine samples were analyzed for 2BAA using GC/MS, and their kinetic parameters were estimated through the curve-fitting method using SAS. Systemically absorbed 2BE was rapidly cleared from blood (t1/2-RAT < 10 min; t1/2-MOUSE < 5 min after the 1-day exposure) independent of exposure concentration. Proportional increases in AUC2BE relative to increases in exposure concentration indicated linear 2BE kinetics. In contrast, the rate of 2BAA elimination from blood decreased as the exposure concentration increased. Nonproportional increases in AUC2BAA also indicated that 2BAA is eliminated following dose-dependent, nonlinear kinetics. Overall, mice eliminated both 2BE and 2BAA from blood faster than rats. Sex-related differences in 2BAA elimination were most significant with rats, in that females were less efficient in clearing 2BAA from the blood. Differences in renal excretion of 2BAA are possibly responsible for the sex-related difference in the 2BAA blood profiles in rats. As exposure continued, the rates of elimination for both 2BE and 2BAA decreased in both species, resulting in longer residence times in the blood. When 19-month-old naive mice were exposed to 125 ppm, 2BE was rapidly cleared from the systemic circulation, exhibiting clearance profiles similar to young mice. However, old mice eliminated 2BAA from blood > 10 times slower than young mice after 1-day of exposure. This delayed elimination of 2BAA in old mice was less obvious after 3 weeks of exposure, suggesting that there might be other factors in addition to the age of animals that could influence the apparent difference in 2BAA kinetics between old and young mice. It was concluded that the elimination kinetics of 2BE and 2BAA following repeated 2BE exposure appear to be dependent on species, sex, age, time of exposure, as well as the exposure concentration.     

Speciation of airborne dust from a nickel refinery roasting operation

Earlier work-related lung and nasal cancer studies included estimates of exposures to different nickel species in the refinery. Based on the metallurgy, only insoluble nickel was believed to be present around the roasters but mixed exposure was assumed in most areas, including the tankhouse. Occasional leaching tests of samples from the roaster area have indicated the presence of soluble nickel. This study reports on five parallel sets of dust samples collected from different floors with standard equipment and treated as follows. Two sets were leached with an ammonium citrate buffer at pH 4.4. Undissolved material was treated with HClO4/HNO3, evaporated to dryness and dissolved in HCl, Ni, Cu, Co, Fe, Se, and As were determined in both fractions. Water soluble Ni was found in all samples, ranging from 5-35%. Sulfate in the solutions correlated nearly stoichiometrically to the total metal content. The three remaining sets were investigated by, respectively, differential leaching, X-ray diffraction and scanning electron microscopy. The percentage of soluble nickel found by differential leaching corresponded well with those obtained by the simplified procedure. X-Ray diffraction analysis showed the presence of NiSO4.6H2O as well as oxides of Ni and Cu. This study indicates mixed exposures also in the roaster area. It also clearly indicates that basing exposure on the metallurgy alone can lead to serious misjudgements. The impact of this new information on the interpretation of cancer incidence at this refinery must await the analysis in an ongoing case-reference study.     

纳米NiO多种制备方法及表征

采用氯化镍和硫酸镍为镍盐,分别与沉淀剂碳酸钠、氢氧化钠、草酸和氨水进行交叉试验,用单相沉淀法制备了不同形貌纳米NiO。采用DSC/TG研究了前驱体粉末的热分解过程,并采用XRD和SEM对热分解产物的组成及形貌进行表征。SEM结果表明:以硫酸镍为镍盐、草酸和氨水为沉淀剂,用单相沉淀法制备纳米NiO效果最佳。在此方案下通过条件试验确定了单相沉淀法制备纤维状纳米NiO的最佳工艺条件。     

Effects of methylphenidate on spatial working memory and planning in healthy young adults

Inhalation of cadmium oxide (CdO) is a significant form of human exposure to cadmium (Cd). Furthermore, there is epidemiological and experimental data relating Cd inhalation with lung cancer. Animal studies indicate that rats are more susceptible to Cd-induced lung cancer than mice, but interstrain sensitivity differences to Cd-induced pulmonary inflammation or carcinogenesis have not been addressed in either species. We compared pulmonary inflammatory processes in Wistar Furth (WF) rats with those in C57 and DBA mice exposed to freshly generated CdO fumes in nose-only inhalation chambers. Animals were exposed to 1 mg Cd/m3 for 3 hr and terminated immediately or 1, 3, and 5 days after exposure. Control animals were exposed to air/argon furnace gases. Cd-induced lung injury was assessed by bronchoalveolar lavage fluid (BALF) analyses, histopathology, and immunohistochemical detection of cell proliferation. Inhalation of CdO resulted in pulmonary inflammatory processes that varied widely across species and strains. C57 mice responded with faster and greater influx of neutrophils and proliferation of alveolar macrophages, type II epithelial cells, and bronchiolar epithelial cells compared to DBA mice or WF rats. DBA mice retained a greater percentage of inhaled Cd in the lungs and presented higher levels of BALF protein than C57 mice or rats. In comparison to mice, WF rats responded with a more transient inflammatory response in BALF parameters and higher degree of acute inflammation in lung tissue. The more pronounced proliferation of alveolar and bronchiolar epithelial cells observed in C57 mice might indicate higher susceptibility of this mice strain to Cd-induced lung carcinogenesis compared to DBA mice or WF rats. Furthermore, the present results of fewer inflammatory cells and lower proliferation of epithelial cells in DBA mice in association with our previous observation of higher Cd-induced metallothionein protein in this strain suggest that DBA might be less susceptible to the pulmonary carcinogenic effects of inhaled Cd than C57 mice or WF rats. We conclude that mice might not necessarily be more resistant than rats to the carcinogenic effects of inhaled Cd, since intraspecies susceptibility differences are strongly suggested by the present data. An extrapolation of this conclusion is that genetic variations in the human population may determine individual sensitivity differences to inhaled Cd.     

Inhalation toxicity of 1,6-hexanediamine dihydrochloride in F344/N rats and B6C3F1 mice

1,6-Hexanediamine (HDA) is a high production volume chemical which is used as an intermediate in the synthesis of paints, resins, inks, and textiles and as a corrosion inhibitor in lubricants. Two- and 13-week studies of the toxicity of the dihydrochloride salt of HDA (HDDC) were conducted in male and female Fischer 344/N rats and B6C3F1 mice using whole-body inhalation exposure. Both species were evaluated for histopathologic and reproductive effects, and rats were examined for clinical chemistry and hematologic changes. In the 2-week inhalation studies, animals were exposed to 10-800 mg HDDC/m3, 6 hr per day. All rats, all female mice, and two of five male mice in the high-exposure group died before the end of the study. Surviving mice in this group had a dose-dependent depression in body weight gain. Clinical signs were primarily related to upper respiratory tract irritation and included dyspnea and nasal discharge in both species. Treatment-related histopathologic lesions included inflammation and necrosis of the laryngeal epithelium of both species and the tracheal epithelium of mice, as well as focal inflammation and ulceration of the respiratory and olfactory nasal mucosa. In the 13-week inhalation studies, animals were exposed to HDDC at concentrations of 1.6-160 mg/m3 for 6 hr per day, 5 days per week. In addition to the base study groups, a supplemental group of rats at each exposure level was included to assess the effect of HDDC on reproduction. No treatment-related changes in organ weights or organ-to-body-weight ratios occurred in rats, and no treatment-related clinical signs or gross lesions were seen in either species. Chemical-related microscopic lesions were limited to the upper respiratory tract (larynx and nasal passages) in the two highest exposure groups and were similar in both species. These lesions included minimal to mild focal erosion, ulceration, inflammation, and hyperplasia of the laryngeal epithelium, in addition to degeneration of the olfactory and respiratory nasal epithelium. HDDC caused no significant changes in sperm morphology or vaginal cytology and no significant adverse effects on reproduction in rats or mice. Hematologic and clinical chemistry changes in rats were minor and sporadic and were not accompanied by related histologic findings. HDDC did not increase the frequency of micronucleated erythrocytes in mice.(ABSTRACT TRUNCATED AT 400 WORDS)     

A patient with WT syndrome and Castleman disease

We studied the mechanisms by which pulmonary solute clearance is affected by lung inflation. We examined the pulmonary clearance of inhaled technetium-99m diethylenetriaminepentaacetic acid (99mTc-DTPA) together with changes in lung volumes in healthy men after applying graded levels of continuous external negative pressure (CNP) and positive end-expiratory pressure (PEEP). The 99mTc-DTPA clearance increased from the baseline during -15 cm H2O CNP (p < 0.005) and during -20 cm H2O CNP (p < 0.001). The 99mTc-DTPA clearance increased during +15 cm H2O PEEP (p < 0.001). However, the changes during both -10 cm H2O CNP and +10 cm H2O PEEP did not differ from the baseline, indicating a threshold effect. On the other hand, changes in FRC during CNP were proportional to the applied pressures and were similar to those during PEEP with corresponding pressures. These results suggest that pulmonary vascular recruitment induced by CNP does not affect pulmonary 99mTc-DTPA clearance. This threshold effect suggests that the increased clearance is due to changes in membrane permeability rather than in the area of the alveolar-capillary interface or the lining layer thickness. We concluded that the effect of lung inflation on solute clearance may be mediated by the changes in membrane permeability.     

Allogeneic stem cell transplantation for multiple myeloma

Ethanol is added to unleaded gasoline as an oxygenate to decrease carbon monoxide automobile emissions. This introduces inhalation as a new possible route of environmental exposure to humans. Knowledge of the pharmacokinetics of inhaled ethanol is critical for adequately assessing the dosimetry of this chemical in humans. The purpose of this study was to characterize the pharmacokinetics of inhaled ethanol in male and female B6C3F1 mice and F344 rats and to develop a physiologically based pharmacokinetic (PBPK) model for inhaled ethanol in mice, rats, and humans. During exposure to 600 ppm for 6 hr, steady-state blood ethanol concentrations (BEC) were reached within 30 min in rats and within 5 min in mice. Maximum BEC ranged from 71 microM in rats to 105 microM in mice. Exposure to 200 ppm ethanol for 30 min resulted in peak BEC of approximately 25 microM in mice and approximately 15 microM in rats. Peak BEC of about 10 microM were measured following exposure to 50 ppm in female rats and male and female mice, while blood ethanol was undetectable in male rats. No sex-dependent differences in peak BEC at any exposure level were observed. Species-dependent differences were found following exposure to 200 and 600 ppm. A blood flow limited PBPK model for ethanol inhalation was developed in mice, rats, and humans which accounted for a fractional absorption of ethanol. Compartments for the model included the pulmonary blood and air, brain, liver, fat, and rapidly perfused and slowly perfused tissues. The PBPK model accurately simulated BEC in rats and mice at all exposure levels, as well as BEC reported in human males in previously published studies. Simulated peak BEC in human males following exposure to 50 and 600 ppm ranged from 7 to 23 microM and 86 and 293 microM, respectively. These results illustrate that inhalation of ethanol at or above the concentrations expected to occur upon refueling results in minimal BEC and are unlikely to result in toxicity.     

化学镀法制备镍包石墨复合粉末

采用化学镀法在石墨粉末表面镀镍制备Ni/石墨复合粉末,采用激光衍射粒度分析、扫描电镜等对Ni/石墨复合粉末的粒度和表面形貌进行表征,研究镀液中主盐硫酸镍、还原剂联氨及活化剂氯化钯的浓度对该复合粉末表面形貌的影响,并对Ni镀层在石墨表面的生长机理进行探讨.结果表明:硫酸镍质量浓度为20 g/L、联氨体积分数为2％时,化学...     

The growth and structure of thin oxide films on cerium ion-implanted nickel

Cerium ions were implanted into a high purity polycrystalline Ni to a dose of 2 × 10¹⁶ Ce⁺/cm². The radiation damage and distribution of Ce in Ni substrate were modified by postimplantation vacuum annealing. The Ce implants significantly decreased the NiO growth rate at 973 K. Thin oxide films formed on implanted Ni were composed of three well-defined sublayers, each with an essentially different microstructure. Cerium was present in the near surface region of the oxide in the form of CeO₂ particles, randomly distributed in NiO matrix, and Ce ion segregants at NiO grain boundaries. The size of CeO₂ particles, formed during the initial stages of exposure to oxygen, affected the inhibition of oxide growth. Vacuum annealing following implantation decreased the beneficial effect of Ce implants by increasing the size of CeO₂ particles. The role of Ce implants in inhibiting grain boundary diffusion in NiO is analyzed. As a result of this study, the growth mechanism of thin NiO films on Ce-implanted Ni is proposed.     

A review of chronic inhalation studies with mainstream cigarette smoke in rats and mice

In this paper, I review the results of a representative selection of chronic inhalation studies with rats and mice exposed to mainstream cigarette smoke and describe the inhalation exposures and the histopathological changes reported by various authors. Many of the studies used nose-only exposure systems, whereas others simply used large whole-body chambers. Smoke-induced epithelial hypertrophy, hyperplasia, and squamous metaplasia were reported in the conducting airways in most of the studies, along with increased numbers of intra-alveolar macrophages that were occasionally associated with alveolar metaplasia. Lung adenomas and adenocarcinomas were reported in only a few of the studies. No statistically significant increase in the incidence of malignant lung tumors was seen in either species as a result of smoke exposure, a finding that does not agree with the results of epidemiological studies in humans. Possible reasons for this lack of correlation are given.     

The effect of inhaled nitric oxide on pulmonary ventilation-perfusion matching following smoke inhalation injury

BACKGROUND: We previously reported that inhaled nitric oxide (NO) improved pulmonary function following smoke inhalation. This study evaluates the physiologic mechanism by which inhaled NO improves pulmonary function in an ovine model. METHODS: Forty-eight hours following wood smoke exposure to produce a moderate inhalation injury, 12 animals were anesthetized and mechanically ventilated (FIO2, 0.40; tidal volume, 15 mL/kg; PEEP, 5 cm H2O) for 3 hours. For the first and third hours, each animal was ventilated without NO: for the second hour, all animals were ventilated with 40 ppm NO. Cardiopulmonary variables and blood gases were measured every 30 minutes. The multiple inert gas elimination technique (MIGET) was performed during the latter 30 minutes of each hour. The data were analyzed by ANOVA. RESULTS: Pulmonary arterial hypertension and hypoxemia following smoke inhalation were significantly attenuated by inhaled NO compared with the values without NO (p < 0.05, ANOVA). Smoke inhalation resulted in a significant increase in blood flow distribution to low VA/Q areas (VA/Q < 0.10) with increased VA/Q dispersion. These changes were only partially attenuated by the use of inhaled NO. The SF6 (sulfur hexafluoride) retention ratio was also decreased by inhaled NO. Peak inspiratory pressures and pulmonary resistance values were not affected by inhaled NO. CONCLUSIONS: Inhaled NO moderately improved VA/Q mismatching following smoke inhalation by causing selective pulmonary vasodilation of ventilated areas in the absence of bronchodilation. This modest effect appears to be limited by the severe inflammatory changes that occur as a consequence of smoke exposure.     

Ventilator-associated lung injury decreases lung ability to clear edema in rats

Ventilator-associated lung injury (VALI) is caused by high tidal volume (VT) excursions producing microvascular leakage and pulmonary edema. However, the effects of VALI on lung edema clearance and alveolar epithelial cells' Na,K-ATPase function have not been elucidated. We studied lung edema clearance in the isolated-perfused rat lung model after ventilation for 25, 40, and 60 min with high VT (peak airway opening pressure [Pao] of approximately 35 cm H2O) and compared them with low VT ventilation (Pao approximately 8 cm H2O), moderate VT ventilation (Pao approximately 20 cm H2O), and nonventilated rats. Lung edema clearance in control rats was 0.50 +/- 0.02 ml/h and decreased after 40 and 60 min of high VT to 0.26 +/- 0.03 and 0.11 +/- 0.08 ml/h, respectively (p < 0.01), but did not change after low VT and moderate VT ventilation at any time point. Lung permeability to small (22Na+, [3H]mannitol) and large solutes (fluorescein isothiocyanate-tagged albumin [FITC-albumin]) increased significantly in rats ventilated for 60 min with high VT, compared with low VT, moderate VT, and control rats (p < 0.01). Paralleling the impairment in lung edema clearance we found a decrease in Na,K-ATPase activity in alveolar type II (ATII) cells isolated from rats ventilated with moderate VT and high VT for 40 min without changes in alpha1 Na,K-ATPase mRNA. We reason that VALI decreases lung ability to clear edema by inhibiting active sodium transport and Na,K-ATPase function in the alveolar epithelium.     

Comparative study of behavior of inhaled samarium and cerium in mice

Distribution of Sm and Ce in mice was investigated after inhalation exposure to their oxide particles of 5 μm diameter and 15 mg/m3.Sm and Ce were mainly distributed in lung,their concentrations decreased with passing time,and their concentrations in lung were correlated with exposure periods.Concentrations of Ce were lower than that of Sm in each point.Sm was also distributed in the other organs and bone but Ce was scarcely detected.These results suggest that the behaviors of Sm and Ce inhaled were different,although their chemical properties are similar.     

Cellular mechanisms of adrenaline-stimulated anion secretion by the mouse endometrial epithelium

As freon is limited in its use as a generator for aerosol inhalation, powder particles are used as an alternative for inhalation therapy. The pulmonary deposition and clearance of inhaled powder particles was studied by positron emission tomography (PET) in ten patients with chronic obstructive pulmonary disease (COPD) and in five normal controls. The powder, 5 microm in mean diameter, was water soluble and labelled with 2-deoxy-2-[18F]-fluoro-D-glucose (18FDG). Powder inhalation was done with single deep inspiration from residual volume to total lung capacity. The initial deposition ratio in the right or left lung field to total inhaled dose, measured by an anteroposterior rectilinear scan, did not differ between normals and COPD patients. Ratios of radioactivity detected within the central and peripheral regions (the central to peripheral ratio) measured by the PET scan was not significantly different between COPD patients (4.8+/-2.6, mean+/-SD) and normals (2.6+/-0.8, mean+/-SD). However, the regional powder deposition in peripheral lung fields measured by the PET scan was significantly more uneven in COPD patients than in normal patients. The clearance rate of 18FDG, defined as the retention ratio of 18FDG activity to the initially deposited 18FDG at 60 and 120 min after inhalation, in the trachea, large bronchi or peripheral lung fields measured by tomographic scan showed a wider variation in COPD patients than in normals. To conclude, inhaled powder tended to be deposited more centrally and was distributed more unevenly in the peripheral lung in chronic obstructive pulmonary disease patients than in normals. This could be a limitation of powder inhalation used for therapy in chronic obstructive pulmonary disease patients.     

Effects of cobalt or nickel on the sympathetically mediated contractile responses in rat-isolated vas deferens

Subchronic (30 days) exposure of rats to Co(NO3)2 or NiSO4 (20 mg.kg-1) in drinking water caused suppression of the isolated vas deferens contractile responses to exogenous adenosine 5'-triphosphate (ATP), noradrenaline, and l-phenylephrine, shifting the concentration-response curves to the relevant agonist to the right. Both metals facilitated the alpha 1-adrenoceptor antagonistic effects of prazosin, which resulted in increased pA2 values for the drug (9.68 +/- 0.13 in controls vs. 10.15 +/- 0.12 in Co(2+)-treated preparations and 12.60 +/- 0.67 in Ni(2+)-treated preparations). The inhibitory effect of clonidine on the contractions in response to low-frequency electrical field stimulation (EFS) in metal-treated preparations was decreased with pD2 values: 10.52 +/- 0.04 in controls, 9.56 +/- 0.13 in Co(2+)-treated preparations and 9.92 +/- 0.16 in Ni(2+)-treated preparations. The monophasic contractile responses to low-frequency EFS (0.1 Hz, 1 ms, 80 V) as well as the first phase of the biphasic contractions after high-frequency long-lasting EFS (300 pulses, 0.1 ms, 40 V, at 4, 8 or 20 Hz) were significantly increased in both groups of heavy metal-treated preparations. Therefore, subchronic exposure to Co2+ or Ni2+ leads to changes in pre- and postjunctional mechanisms underlying the sympathetically mediated contractile activity of isolated rat vas deferens.     

Pharmacokinetics of and CYP1A induction by pyridine and acetone in the rat: interactions and effects of route of exposure

1. Male Sprague-Dawley rats were exposed to either pyridine, acetone or a combination of both compounds by either intraperitoneal administration (100 mg/kg pyridine or 400 mg/kg acetone) or whole-body inhalation (200 ppm pyridine or 1000 ppm acetone). Plasma and tissue levels of both compounds were determined by gas chromatography/mass spectrometry. 2. Both chemicals were well distributed in the tissues examined following either route of exposure, with concentrations in the order kidney > liver > plasma > lung. 3. Plasma half-life of pyridine was 7 h following a single 100 mg/kg dose of the compound, and 8 h following the last dose of a 3-day, 8 h/day exposure to a 200 ppm inhalation dose of the compound. 4. Plasma half-life of acetone was 4 h and was independent of the route of exposure. 5. The pharmacokinetics of pyridine was not affected by co-exposure to acetone. Similarly, the pharmacokinetics of acetone was not affected by co-exposure to pyridine. 6. Ethoxyresorufin O-deethylase activity in lung and liver and methoxyresorufin O-demethylase activities in liver were induced by pyridine but not by acetone at the doses examined. Pyridine-induced ethoxyresorufin O-deethylase activity was higher following inhalation exposure than following i.p. administration of pyridine but did not parallel tissue levels of the compound.     

Tissue specificity of spontaneous point mutations in lambda supF transgenic mice

Abuse of nitrite inhalants, widespread among male homosexuals, has been identified by epidemiological studies as an independent risk factor for AIDS and for Kaposi's sarcoma. Subchronic exposure of mice to inhaled isobutyl nitrite was previously found to impair the tumoricidal activity of peritoneal macrophages. Because inhalants would be expected to have the greatest effects on cells in the lung, alveolar macrophages from exposed mice were examined in this study. Mice were exposed to 900 ppm isobutyl nitrite in an inhalation chamber for 45 min/day for 14 days. Following this treatment, the lungs of exposed mice had large increases in cellularity, both in the alveolar septa and within the alveoli. Bronchoalveolar lavages also contained increased numbers of cells. Alveolar macrophages collected from treated mice had increased tumoricidal activity compared with controls and produced higher levels of inducible nitric oxide and tumor necrosis factor-alpha (TNF-alpha). The frequency of alveolar cells secreting TNF-alpha was increased ninefold in mice exposed to the inhalant. Cell influx into the lung, as indicated by the presence of red blood cells in lung lavages, was evident after only a single 45-min exposure to inhaled isobutyl nitrite at doses as low as 300 ppm.     

The diffusion and solubility of oxygen in solid nickel

Solid-state electrochemical measurements using various experimental procedures were made with the double cell: $$ Ni + NiO|ZrO_2 + Y_2 O_3 |Ni + \underline O |ZrO_2 + Y_2 O_3 |Ni + NiO $$ to determine the diffusivity and thermodynamic functions of oxygen dissolved in solid nickel. Non-steady state diffusion of oxygen in the specimen was caused by applying a preselected potential between the reference and specimen electrodes and was monitored by measuring time-dependent potentials and/or currents. The following results were obtained for the diffusivity of oxygen and the solubility of oxygen in nickel in equilibrium with NiO: $$D{\text{ = 4}}{\text{.9 }} \times {\text{ 10}}^{{\text{ - 2}}} {\text{ exp}}\left( {{\text{ - }}\frac{{{\text{164 kJ/mole}}}}{{{\text{R}}T}}} \right){\text{cm}}^{\text{2}} /{\text{sec (850 to 1400 }}{}^{\text{o}}{\text{C)}}$$ $$C_{\text{O}}^s {\text{ = 8}}{\text{.3 exp}}\left( { - \frac{{55{\text{kJ/mole}}}}{{{\text{R}}T}}} \right){\text{at}}{\text{. pct (800 to 1000 }}{}^{\text{o}}{\text{C)}}$$ The thermodynamic and transport behaviors of oxygen in solid nickel were fairly well described by a simple quasi-regular model and an interstitial diffusion model, respectively.     

Riluzole interacts with voltage-activated sodium and potassium currents in cultured rat cortical neurons

Inhaled nitric oxide is a selective pulmonary vasodilator used for the treatment of pulmonary hypertension. The potential adverse effects of inhaled nitric oxide are unknown and represent the focus of the present studies. Whereas inhalation of nitric oxide (10 to 100 ppm, 5 h) by Balb/c mice had no effect on the number or type of cells recovered from the lung, a dose-related increase in bronchoalveolar lavage protein was observed, suggesting that nitric oxide induces alveolar epithelial injury. To determine if this was associated with altered alveolar macrophage activity, we quantified production of reactive oxygen and nitrogen intermediates by these cells. Interferon-gamma, alone or in combination with lipopolysaccharide (LPS), induced expression of inducible nitric oxide synthase (iNOS) protein and nitric oxide production by alveolar macrophages. Cells from mice exposed to 20 to 100 ppm nitric oxide produced significantly more nitric oxide and expressed greater quantities of iNOS than cells from control animals. Superoxide anion production and peroxynitrite generation by alveolar macrophages were also increased after exposure of mice to nitric oxide. This was correlated with increased antinitrotyrosine antibody binding to macrophages in histologic sections. Taken together, these data demonstrate that inhaled nitric oxide primes lung macrophages to release reactive oxygen and nitrogen intermediates. Increased production of these mediators by macrophages following inhalation of nitric oxide may contribute to tissue injury.