Masayoshi Kitabatake

Metabolic fate of nitric oxide

SummaryThe metabolic pathway of inhaled NO in rats was investigated with 15NO. After 15NO exposure, the content of the 15N (atom % excess) in blood, red cells, serum, each organ tissue (perfused with saline solution) and urine were estimated. The contents of 15N in the samples of blood, serum, red cells, and urine were relatively high and those of lung, trachea, liver, kidney, and muscle were low.The rat blood samples 1 h after 15NO combined blood injection were analyzed. Greater parts of the 15N in the serum were in a fraction of the ultrafiltrate and the amounts of NO3−in the serum were remarkably elevated compared with those of the control rats.At 24 h and 48 h after 15NO combined blood injection, the urine samples were collected. Most of the 15N in the urine was found within 24 h.Red cells from the 15NO exposed rats were washed (mixed and incubated) with the saline solution or the serum from untreated rats. The 15N in the cells was easily extracted into the solution or serum, but the 15N in the serum from the exposed animals was scarcely transferred to the red cells.Throughout the experiments, it was supposed that inhaled NO primarily reacted with hemoglobin and was changed to NO2−and NO3−. Then the metabolites were transferred to serum, part of these reacted with tissues and the others were excreted in urine in the form of NO3−.

Mortality from Asthma and Chronic Bronchitis Associated with Changes in Sulfur Oxides Air Pollution

Death certificates issued in Yokkaichi, Japan, during the 21 yr from 1963 until 1983 were surveyed to determine the relationship between changes in air pollution and mortality due to bronchial asthma and chronic bronchitis. The following results were obtained. In response to worsening air pollution, mortality for bronchial asthma and chronic bronchitis began to increase. Mortality due to bronchial asthma decreased immediately in response to improvement of pollution, whereas mortality due to chronic bronchitis decreased to the level in the control area 4 to 5 yr after the concentration of sulfur dioxide (SO2) began to satisfy the ambient air quality standard. In the polluted area, mortality due to bronchial asthma in subjects who were 20 yr of age was higher during the period in which higher concentrations of sulfur oxides were prevalent.

Biotransfornation of nitric oxide, nitrite and nitrate

SummaryBiotransformation of NO, nitrite and nitrate was investigated in rats and mice in a 15NO inhalation experiment and intraperitoneal injection experiments of 15N-nitrite and 15N-nitrate, and the following results were obtained:(1)Rats were forced to inhale 15NO (145 ppm,123 minutes) or were given an intraperitoneal injection of 15N-nitrite (2 mg animal−1 as 15N) or 15N-nitrate (2mg animal−1 as 15N), and determination of 15N recovery in urine was made up to 48 h later. The results were 55, 53 and 78% of the inhaled or injected 15N, respectively.(2)15N-nitrate in the urine was converted into a 6-nitro derivative of 3,4-xylenol and its identification and quantitative determination were made by the GGMS method. As to 15N-urea in the urine, identification and quantitative determination were made by the urease method. 15N was present in the urine of rats after 15NO inhalation in the form of N03− and urea. 75 and 24% respectively. In the urine of rats injected with 15N-nitrite, about 20% of unidentified 15N-compounds not discovered in the inhalation experiment was found. The content of 15N-urea in the urine after injection with 15N-nitrate was lower than that after injection with 15N-nitrite.(3)When 15N-nitrite (0.617 mg animal−1 as 15N) was injected intraperitoneally in mice, 60.7, 7.8 and 0.3% of the injected 15N were found in the urine, feces and exhaled gas (NO, N02 and NH3 in the gas were caught) up to 48 h after injection respectively, and 1.6% was found in the body 48 h after injection, but the remaining 30% of 15N could not be recovered.

Seasonal mood variation among Japanese residents of Stockholm

Depressive symptoms estimated by the Beck Depression Inventory (BDI) were examined in winter and summer in a total of 242 Japanese adults staying less than 2 years or longer than 10 years in Stockholm, where the length of daylight changes dramatically throughout the winter and summer seasons. In spite of the difference in the period of residency, both groups of subjects showed more mental and somatic depressive symptoms in the winter than in the summer. Moreover, the winter BDI score of long stayers was significantly higher than that of short stayers. Accordingly, our results suggest that, although seasonal mood variation is essentially produced by a chronobiological factor, Swedish lifestyle to which long stayers have been accustomed also influences the seasonal mood variation.

Effects of inhaled nitric oxide in rats with chemically induced pulmonary hypertension.

To determine the model animal with pulmonary hypertension in which nitric oxide (NO) inhalation reduces pulmonary arterial pressure (PAP), we examined the inhalation of 20-100 ppm NO gas on normal rats and rats with monocrotaline induced pulmonary hypertension. In the control group, mean PAP showed no change after spontaneous breathing of NO at the concentration of 20 to 100 ppm for 5 min. On the contrary, in both the severe (mean PAP > 40 mmHg) and moderate (mean PAP < 40 mmHg) pulmonary hypertensive groups, NO inhalation produced a prompt reduction of the mean PAP which had been elevated by monocrotaline. 20 ppm NO inhalation reduced mean PAP from 64.4 +/- 3.7 mmHg to 56.2 +/- 4.4 mmHg (mean +/- SEM, P < 0.01) in the severe pulmonary hypertensive group, from 31.0 +/- 2.0 mmHg to 24.2 +/- 0.9 mmHg in the moderate pulmonary hypertensive group (mean +/- SEM, P < 0.05). The onset of the reduction of mean PAP occurred within 30 sec after the start of NO inhalation and maximum reduction occurred within 4 min. 20 ppm NO inhalation significantly reduced mean PAP, and mean PAP was reduced dose-dependently at the concentration of 20 to 60 ppm and reaction to NO was almost constant at the concentrations of over 60 ppm.

Effect of phenylmethylsulfonyl fluoride administration prior to and following leptophos administration on electrolyte concentration and enzyme activity in hen serum

We observed acute toxicity, delayed neurotoxicity, disappearance of leptophos from tisuues and biochemical changes in four groups of hens: a group given only 30 mg/kg leptophos (iv) as the ‘leptophos group’, two groups given a treatment of 30 mg/kg phenylmethylsulfonyl fluoride (PMSF) (sc) 24 hr prior to (as the ‘pretreated group’) and following (as the ‘posttreated group’) administration of the same dose of leptophos as the leptophos group, and a group given a vehicle only as the ‘control group’. All groups other than the control group showed acute toxicity. The scores for organophosphate-induced delayed neurotoxicity (OPIDN) in the posttreated group reached the maximal level on the 16th day after leptophos administration and those in the leptophos group reached the maximal level on the 25th day. Serum acid phosphatase (AcP) activities in the leptophos group and the posttreated group were significantly lower than that in the control group (p<0.05) on the 6th day after leptophos administration and then recovered to the normal level on the 15th day. In these two groups, serum creatine phosphokinase (CPK) activity was significantly higher (p<0.01) and the concentration of serum Ca2+ was significantly lower (p<0.05) than in the control group on the 15th day after leptophos administration. Serum leucine aminopeptidase (LAP) activity in the posttreated group was significantly lower than that in the control group (p<0.01). As for the significant changes by time interval between the 6th and the 15th days after leptophos administration, CPK activity was elevated and serum Ca2+ reduced in both the leptophos group and the posttreated group, and LAP activity was also reduced in the posttreated group. The courses of leptophos disappearance in several tissues of these hens were similar in the 3 groups. These results suggest that the treatment by PMSF prior to or following the administration of leptophos can significantly modify not only clinical signs of OPIDN but also changes of several biochemical indices accompanied by OPIDN. Furthermore, it is possible to expect that these biochemical indices can provide some valuable clues for exploring the modification of OPIDN by PMSF treatment.

Effects of exposure to sulfate aerosols and antigen on breathing curve patterns of Guinea pigs

We investigated the effects of ammonium sulfate aerosols on asthmatic dyspnea (immediate type) induced by repeated inhalation of a mixture of bovine serum and egg albumin and on the nonspecific responsiveness of the airway tract to acetylcholine. Guinea pigs were exposed to sulfate aerosol in concentrations of 0.2, 0.4, and 2.0 mg/m3 and to 0.2 mg/m3 sulfate aerosol combined with 0.1 ppm of SO2. The exposure time was 2 h/d, 5 d/wk, 38 times in all. The animals were successively exposed to aerosol (for 2 h) and, after 30 min, to the spraying of albumin solution 3 times per week, 7 or 9 times in all. Breathing curves were continuously recorded by a body plethysmograph system during the sensitization periods. The experiments showed that the degree of asthmatic dyspnea in guinea pigs was increased by the exposure to aerosol, and that there is a quantitative relation between the severity of the dyspnea and extent of the exposure. Exposure in the combination with SO2 showed no effect at the concentration studied. Following the exposure experiment, each group of animals was exposed to the spraying of acetylcholine. The sensitivity to acetylcholine increased at aerosol concentrations of 0.4 and 2.0 mg/m3.

The effects of exposure to NO or NO2 and an antigen on the breathing curve pattern in guinea pigs

Abstract The effect of NO and NO2 of inducing an asthmatic breathing difficulty following inhalation of albumin of different species and the effect on the hypersensitivity toward acetylcholine in the respiratory tract were investigated to study the relation between asthma and NO, NO2. Two experimental groups, the group exposed to NO (average 5.02 ppm) and the group exposed to NO2 (average 5.00 ppm) were prepared. The exposures to NO or NO2 gas (30 min) and, after 20 min, the albumin solution spray were repeated ten times, twice a week. For these exposures, breathing curves were continuously autorecorded with a body plethysmograph to ascertain the intensity of the asthmatic respiratory difficulty. Comparison showed that animals with stronger patterns of asthmatic dyspnea were greater in number when exposed to NO or NO2 and albumin (NO or NO2 group) than when exposed only to albumin (control group). Following all exposures, each group was expos d to an acetylcholine spray of the same concentration. In the case of the NO, NO2 groups, an increase in the susceptibility of the airway tract to acetylcholine could be observed.

Composition of aerosols in an industrialized area of northeastern China

Abstract Surface level aerosol samples were collected utilizing conventional high volume air sampler in the highly industrialized area of Shenyang, China, located in the northeastern part of the country. Sampling was conducted in the severely polluted Tiexi District area on December 25, 1995 and again from August 23–30, 1997. The average SO2 and TSP concentrations obtained during the summer was 38 ppb and 388μg/m3, respectively. SO4 2‐, NO3 ‐ and Cl‐ were the detected water‐soluble anions with respective summerconcentrations of 3.6–10.6μg/m3, 3.2–6.5μg/m3 and 4.5–7.8μg/m3. In addition, elevated levels of heavy metals such as iron, lead, and zinc in aerosols were noted, which most likely resulted from the combustion of coal and other fuels and/or emissions associated with nearby industrial facilities. As expected, concentration levels of TSP, water‐soluble ions and heavy metals were found to increase during the winter months.

Effects of exposure to NO2 or SO2 on bronchopulmonary reaction induced by Candida albicans in guinea pigs

The effects of NO2 or SO2 on the bronchopulmonary reactions induced by Candida albicans in guinea pigs were evaluated. Thirty-six guinea pigs (3 groups of 12 animals each) were sensitized with intraperitoneal injection of 10 mg of C. albicans, given twice. Two groups of animals were exposed to about 5 ppm of NO2 or SO2 for 4 h/d, 5 d/wk; this exposure was conducted a total of 30 times during the study. The third group served as the control and was not exposed to these pollutants. Two weeks after the second sensitization, all the animals were subjected to inhalation exposure to C. albicans. For 42 h after the antigen challenge, the respiratory rates and expiration/inspiration ratios of the animals were automatically monitored. The number of animals showing tachypnea was significantly higher in the NO2 exposure group than in the control from 15 h after antigen challenge. In the SO2 exposure group, the number of animals showing prolonged expiration or prolonged inspiration, or both, was significantly higher than that in the control group, and the symptoms were observed from approximately 15 h after antigen challenge. These findings showed that delayed-type dyspneic symptoms in guinea pigs were increased by exposure to NO2 or SO2, although the symptoms and degree of dyspnea were different for the two gases.