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V L Kinnula

Publications and source records attributed to V L Kinnula.

At least 73 records · Page 4Linked to original sources
PubMed1994

Primary and immortalized (BEAS 2B) human bronchial epithelial cells have significant antioxidative capacity in vitro.

Antioxidant enzymes located in the bronchial epithelium can be expected to be important in protecting these cells against both endogenous and exogenous oxidants. In this study, human bronchial epithelial cells were isolated and cultured from specimens obtained from donors for lung transplantation. The levels and relative importance of different antioxidant enzymes were also assessed using an immortalized human bronchial epithelial cell line (BEAS 2B cells). Immunocytochemical studies showed a similar pattern of intracellular localization with the moderate degrees of labeling for Mn superoxide dismutase (SOD), CuZn SOD, and catalase in freshly isolated bronchial epithelial cells, bronchial epithelial cells in primary culture, and BEAS 2B cells. CuZn SOD and catalase decreased in labeling density whereas Mn SOD was unchanged when bronchial epithelial cells were placed in primary cultures. In contrast, Mn SOD and catalase were decreased in BEAS 2B cells compared with primary cultures. Although Mn SOD was low in BEAS 2B cells, it could be significantly induced by tumor necrosis factor treatment. Biochemical analysis showed remarkably similar catalase and glutathione reductase activities in primary cultured epithelial cells and BEAS 2B cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Amitrole↗
PubMed1994

Respiratory viral and Mycoplasma infections in patients hospitalized for acute asthma.

We evaluated the involvement of viral and Mycoplasma infections in severe attacks of asthma in 112 adult patients admitted to Oulu University Central Hospital for an exacerbation of asthma, during a period of one year. The total number of admissions was 151, and specimens for viral identification were collected from 142 of these. Although the methods for diagnosis of rhinoviruses and coronaviruses were lacking, the diagnosis of a viral or Mycoplasma infection was confirmed in 41 patients (29%) by one or more of the three methods; viral serology, viral culture from a throat wash or viral antigen detection from a nasopharyngeal aspirate. Thirty six of these patients (88%) with confirmed infection also had symptoms suggestive of a viral infection. We conclude that viral and Mycoplasma infections are so often involved in severe asthma attacks of adults that they may play an important role in the induction of such attacks.

Acute Disease↗
PubMed1993

Association of severe asthma attacks with weather, pollen, and air pollutants.

BACKGROUND: The association between exacerbations of asthma and weather or air pollution is not well understood. The relationships between visits to the emergency room for asthma attacks and the meteorological, aerobiological, and chemical characteristics of the outdoor air have been evaluated. METHODS: The number of daily attendances for asthma attacks at the emergency room of Oulu University Central Hospital was recorded over one year together with daily meteorological readings (temperature, humidity, barometric pressure, rainfall), levels of air pollutants (nitrogen dioxide (NO2), sulphur dioxide (SO2), hydrogen sulphide (H2S), total suspended particles (TSP)), and pollen counts (birch, alder, pine, willow, total pollen). The relationship between the number of attendances and the measured variables was then analysed by multiple regression and stepwise discriminant analysis. RESULTS: The total number of attendances during the year was 232, with lower figures in summer and higher in winter. No association was found between visits for asthma attacks and airborne pollen levels or meteorological factors except for temperature, which had a low inverse correlation with attendance. The most significant correlations were found between asthma visits and the levels of NO2; those for SO2, TSP, and H2S were also significant. Intercorrelations between SO2 and temperature or NO2 and between temperature and TSP or NO2 were also found, but only NO2 correlated significantly with attendances after standardisation for temperature. CONCLUSIONS: Increased levels of pollutants, especially NO2, were associated with attacks of asthma, but the explanation for this is unclear. Air pollen levels were not associated with asthma attacks and only temperature among the meteorological factors had a small association with asthma.

Adolescent↗
PubMed1993

Elevated ventilatory equivalents during exercise in patients with hyperventilation syndrome.

In hyperventilation syndrome (HVS), hyperventilation is often provoked by exercise. This study was undertaken to investigate gas exchange parameters and their correlation to arterial blood gas values in HVS patients during exercise. Ventilatory equivalents for oxygen (VE/VO2) and carbon dioxide (VE/VCO2) were significantly higher in HVS patients than in the controls. (VE/VO2) during light exercise (40-50 W) was 23.1 +/- 2.7 (n = 10) in the controls and 35.2 +/- 8.2 (n = 10) in the HVS group (p < 0.01). VE/VCO2 during light exercise was 30.0 +/- 3.3 in the controls and 41.8 +/- 6.0 in the HVS group (p < 0.01). In HVS, significantly correlations were observed between VE/VCO2 and PaCO2, and between VE/VO2 and PaCO2 during both light and maximal exercise (p < 0.02). The findings suggest that exercise testing can be used to aid HVS diagnosis without invasive arterial cannulation.

Adult↗
PubMed1993

Modulation of hydrogen peroxide release from vascular endothelial cells by oxygen.

We have investigated factors that regulate hydrogen peroxide (H2O2) release from vascular endothelial cells. Endothelial cells produce H2O2 at an intracellular site in the vicinity of peroxisomes and at a second site near the cell surface that is inaccessible to intracellular catalase or glutathione peroxidase. Regulation of H2O2 generation at the intracellular site was studied using aminotriazole, which inactivates catalase in the presence of H2O2. Regulation of H2O2 generation at the second site was studied by measuring H2O2 release into the medium. The rate of H2O2 release was constant over 2 h when cells were incubated in room air. Changing O2 levels in the atmosphere from 0% to 10% O2 resulted in a threefold increase in the rate of H2O2 release. Elevation of O2 levels from 10% to 95% O2 produced no further enhancement in the rate of release. Preincubation of cells under hypoxic conditions did not lead to an exaggerated rate of H2O2 release when cells were returned to room air. Pretreatment of cells with exogenous H2O2 inhibited subsequent H2O2 release while pretreatment with catalase enhanced H2O2 release. Although arachidonic acid transiently enhanced the rate of H2O2 release through a mechanism dependent on PGH synthase, basal H2O2 release was independent of this enzyme. Neither hypoxia, hyperoxia, or hypoxia followed by reoxygenation altered H2O2 generation at the intracellular site accessible to peroxisomal catalase. These data demonstrate that H2O2 release from endothelial cells is responsive to changes in O2 concentrations over a narrow range. The mechanisms involved are subject to product inhibition and appear to be saturated at 10% O2 in the atmosphere.

Animals↗
PubMed1992

Oxidants and antioxidants in alveolar epithelial type II cells: in situ, freshly isolated, and cultured cells.

Antioxidant enzyme activities, H2O2 clearance, and H2O2 generation by rat alveolar epithelial type II cells were compared between in situ, freshly isolated (6 h ex vivo), and cultured cells (48 h ex vivo). Immunocytochemical studies did not show changes in catalase, Mn superoxide dismutase, or CuZn superoxide dismutase labeling density in cytoplasm, peroxisomes, or mitochondria. Numbers of peroxisomes and mitochondria per cell decreased in cultured cells. Biochemical studies showed that cell culture resulted in a significant decrease in activities of catalase (49%), glutathione reductase (50%), glutathione peroxidase (74%), and in the capacity of the cells to scavenge extracellular H2O2. Addition of the specific catalase inhibitor, aminotriazole, decreased the rate of consumption of exogenously added H2O2 in freshly isolated cells but not in cultured cells. Neither aminotriazole nor 1,3-bis (2-chloroethyl)-1-nitrosourea, which inactivates glutathione reductase, altered H2O2 consumption by cultured cells. The rate of extracellular H2O2 release in both freshly isolated and cultured cells was 0.71 nmol.min-1.mg protein-1. It can be concluded that levels of some antioxidant enzymes fall in cultured alveolar epithelial type II cells, and that, although catalase likely plays a significant role in protection of freshly isolated cells against oxidant stress, this pathway may be less important after culture.

Amitrole↗
PubMed1992

Release of reactive oxygen species by guinea pig tracheal epithelial cells in vitro.

Regulatory and stimulatory mechanisms of H2O2 release from guinea pig tracheal epithelial cells were investigated. Cells in primary culture maintained in a previously described air-liquid interface system released H2O2 to the extracellular space only from the apical side of the cells. The rate of release was 0.044 +/- 0.003 nmol.min-1.mg protein-1. H2O2 release could be stimulated significantly during a 30-min incubation period with phorbol myristate acetate (PMA) and platelet-activating factor (PAF). A stimulatory effect of PAF was achieved at concentrations greater than 100 nM and with PMA at concentrations greater than 10 ng (16 nM). When protein kinase C was inactivated with staurosporine, the responses to both PAF and PMA were abolished, whereas the cyclooxygenase inhibitor, indomethacin, did not affect H2O2 generation. When guinea pig tracheal epithelial cells were exposed to sublethal concentrations of extracellular H2O2 (30 microM), H2O2 was detoxified from both apical and basal sides, H2O2 removal being significantly more rapid from the apical side of the cells. These results suggest that tracheal epithelial cells can be stimulated to generate reactive oxygen species into the airway lumen and that this occurs in response to inflammatory mediators that act through protein kinase C. Luminal H2O2 release may have developed as a defense mechanism against microbes, and, similarly, luminal detoxification of H2O2 could represent an important mechanism of modulation of airway inflammation in response to oxidant stress.

Analysis of Variance↗
PubMed1992

Regulation of hydrogen peroxide generation in cultured endothelial cells.

Endogenous hydrogen peroxide (H2O2) release from aortic endothelial cells was studied in the presence of antioxidant enzyme inhibitors, mitochondrial inhibitors, a microsomal cytochrome P-450 inhibitor, and after oxidative stress induced with H2O2 or menadione. Extracellular H2O2 generation was determined spectrofluorometrically using 3-methoxy-4-hydroxy phenylacetic acid, and intracellular H2O2 production (in or near peroxisomes) was measured indirectly using aminotriazole, which inactivates catalase in the presence of H2O2. Extracellular H2O2 release was 0.079 +/- 0.005 nmol/min/mg protein in Hanks' balanced salt solution, was constant during a 120-min incubation period, and was not affected by the cell passage number. The half-life for catalase inactivation with aminotriazole was 23 min. Inhibition of catalase, glutathione reductase, or gamma-glutamylcysteine synthetase did not change the rate of extracellular release of H2O2. Furthermore, inhibition of the mitochondrial respiratory chain (rotenone, antimycin A) or microsomal cytochrome P-450 (8-methoxypsoralen) did not change extracellular H2O2 release or intracellular H2O2 production (at peroxisomes) by endothelial cells or cells in which glutathione reductase was inactivated. When the cells were exposed to exogenous H2O2 (30 microM), extracellular H2O2 was scavenged primarily by the glutathione redox pathway. Exogenously added H2O2 (100 microM) changed intracellular H2O2 production (in or near peroxisomes) only when the glutathione redox cycle was inactivated. Menadione (20 microM), which undergoes intracellular redox cycling, increased extracellular H2O2 release almost 4-fold to 0.3 nmol/min/mg protein. Furthermore, menadione increased peroxisomal H2O2 levels and decreased the half-life for catalase inactivation in the presence of aminotriazole to 13 min. Catalase inhibition increased extracellular H2O2 release during menadione treatment, indicating that H2O2 can diffuse across the plasma membrane during oxidant stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Amitrole↗
PubMed1992

Antioxidant defense mechanisms in cultured pleural mesothelial cells.

The role of different antioxidant pathways in cultured rat pleural mesothelial cells was studied by exposing the cells to various hydrogen peroxide (H2O2) concentrations and by measuring H2O2 cell cytotoxicity and the capacity of the cells to scavenge H2O2. The antioxidant enzymes, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, and catalase were analyzed biochemically. Catalase and CuZn superoxide dismutase were localized by immunocytochemistry. To enable investigation of the glutathione redox cycle and catalase pathways, glutathione reductase was inactivated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and catalase was inactivated with aminotriazole. When the cells were exposed to a low, sublethal (0.030 mM) H2O2 concentration, glutathione reductase but not catalase inactivation resulted in a decreased capacity to remove H2O2 from the extracellular medium. When the cells were exposed to a high (0.25 mM) H2O2 concentration, H2O2-scavenging capacity decreased remarkably when catalase was inactivated. When the cells were exposed to 0.1 to 0.5 mM H2O2, cell cytotoxicity (lactate dehydrogenase release) increased significantly if glutathione reductase was inactivated; catalase inactivation resulted in a significant cytotoxicity only at high (greater than or equal to 0.25 mM) H2O2 concentrations. Immunocytochemical studies showed that the cells, both in situ and in vitro, contained low amounts of catalase. This suggests that the results of the catalase-inhibition studies are probably not due to a change in the characteristics of the cells in culture. 3-Aminobenzamide is a compound that is known to prevent NAD depletion through inhibition of poly(ADP-ribose) polymerase during oxidant stress. When intact cells were treated with different antioxidants and exposed to 0.5 mM H2O2, both catalase and 3-aminobenzamide protected the cells completely.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Hydrogen peroxide production by alveolar type II cells, alveolar macrophages, and endothelial cells.

Extracellular H2O2 release and intracellular H2O2 production were determined in rat lung alveolar macrophages, rat alveolar type II cells, and cultured bovine aortic endothelial cells. Isolated macrophages (5 h ex vivo) released 3.1 +/- 0.09 nmol H2O2.min-1.mg cell protein-1, freshly isolated (5 h ex vivo) type II cells released 0.7 +/- 0.07 nmol H2O2.min-1.mg protein-1, and cultured endothelial cells released 0.06 +/- 0.005 nmol H2O2.min-1.mg protein-1. The rate of extracellular H2O2 release decreased rapidly over time in both fresh macrophages and freshly isolated type II cells. When the measurements were repeated at different times ex vivo, the decrease was greater than 20%/h, and H2O2 release was almost undetectable 12 h ex vivo. The decrease occurred while lactate dehydrogenase release, catalase activity, and intracellular H2O2 production remained unchanged. Catalase activity was 59.3 +/- 4.9 nmol O2 produced.min-1.mg protein-1 in type II cells, 13.2 +/- 1.8 in macrophages, and 11.4 +/- 2.7 in endothelial cells. Aminotriazole is a compound that inhibits catalase in the presence of H2O2 at a rate that is proportional to the rate of intracellular H2O2 production in or near peroxisomes. Incubation of the cells with aminotriazole led to a rapid inhibition of catalase. In 15 min the reduction of catalase activity was 69% in type II cells, 53% in macrophages, and 37% in endothelial cells. When freshly isolated type II cells were exposed to hyperoxia (95% O2) for 30 min, no changes in the rate of either intracellular H2O2 production or extracellular H2O2 release were seen.

Animals↗
PubMed1991

Emergency room visits for acute attacks of asthma: characterization of patients and visits.

To characterize asthma emergencies, all patients attending the hospital because of an asthma attack in 1 year were studied. Of the 212 patients concerned, 148 attended the hospital once, 34 twice and 30 three times or more. The total number of visits was 351. The mean age of the patients was 50 (15-85) years, and 32% of those under 65 years were receiving a pension because of asthma. Eleven patients (5%) had drinking problems, and 62 (29%) had treatment for other diseases. Atopy was diagnosed in 83 patients (39%). Of the patients with one, two or more numerous visits 39, 74 and 90%, respectively, were taking oral steroids, whereas the corresponding figures for those using inhaled steroids were 34, 71 and 61%. Medical treatment seemed to be inadequate more often among the frequent visitors. Seasonal variation in visits was evident, the rates being lowest in July and highest in March. Time-of-day variation was also found, visits being most common from 10 to 11 a.m.

Acute Disease↗
PubMed1985

Skeletal muscle activity of alcohol-treated rabbits in immersion hypothermia: adenine nucleotide concentrations and phosphorylation state.

The effects of alcohol injection (0.5 g . kg-1 i.v.) on the core cooling and rewarming rates, concentration of the adenine nucleotides, and the phosphorylation state of the adenylate system (ATP/ADP X P) were studied in the skeletal muscle of anesthetized rabbits immersed in ice-cold water. NaCl-injected rabbits immersed in ice-cold water were used as cold controls, alcohol-treated animals at room temperature (20 degrees C) as alcohol warm controls, and NaCl-injected animals at room temperature as anesthesia controls, respectively. The fall of core temperature to 32 degrees C in the alcohol-treated rabbits and the cold controls took about 40 min. During this time the temperature of the alcohol warm and anesthesia controls fell by about 1 degree C. No difference in the rewarming rate was observed between the alcohol-treated and cold control rabbits. Serum glucose concentration was elevated in the cold controls (from 5.9 to 8.3 mmol/l) but not in the alcohol-treated rabbits. Cold exposure reduced the phosphorylation state in the skeletal muscle of the alcohol-treated rabbits by 32% (P less than 0.05), but the decrease (6%) was not significant in the cold controls. After rewarming the phosphorylation state decreased in the above groups by 71% and 15%, respectively, as compared with the initial values. No significant changes in the phosphorylation state were found in the warm control animals. The redox state of the cytosol in the skeletal muscle or liver did not change, nor was there any change observed in the arterial pO2 or pCO2 concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1981

Effects of hypoxia and fasting on the cytochrome concentration in intestinal epithelial villous cell mitochondria. Role of changes in the life-span of the cells.

The effects of hypoxia in vivo (40.8 kPa barometric pressure up to 120 h) and fasting on the characteristics of intestinal epithelial villous cell mitochondria and the turnover of epithelial villous cells and mitochondria were studied in rats. Using cells and mitochondria isolated in the isotonic mannitol medium, it was found that 24-h hypoxia or fasting did not alter the mitochondrial cytochrome content, but 48-h hypoxia or fasting led to increases of 70% and 37% in the cytochrome aa3 concentration in the hypoxic and fasting animals respectively. The turnover of intestinal epithelial cells was studied by observing the labelling kinetics of the cells with 3H-thymidine and the turnover of the cell and mitochondrial proteins with (guanido-14C)-arginine or 3H-leucine. The decay in thymidine radioactivity obeyed exponential kinetics from which half-lives of 1.15, 1.31 and 1.53 days were calculated in the control, fasting and hypoxic animals respectively. The half-lives for total cellular protein were 1.31, 1.54 and 1.54 days respectively when calculated from the (guanido-14C)-arginine experiments, or 0.69, 0.75 and 0.99 days when calculated from the leucine experiments. The labelling experiments with (guanido-14C)-arginine indicated that the turnover of mitochondrial proteins in intestinal epithelial cells is the same as that of the cells themselves. Since the turnover of mitochondrial proteins in other tissues is shown to be a relatively slow process, the increase in the cytochrome concentration in the intestinal cells of the hypoxic rats must be due to the longer life of the cells, which allows for the synthesis of larger amounts of the mitochondrial components.

Animals↗
PubMed1978

Effect of chronic hypoxia on hepatic triacylglycerol concentration and mitochondrial fatty acid oxidizing capacity in liver and heart.

The effect of moderated hypoxia (50.5 kPa air) and severe hypoxia (40.8 kPa air) in vivo liver and heart triglyceride concentration and mitochondrial respiration rates was studied. Liver triglyceride concentrations increased in severe hypoxia from 7.3 mumol/g wet weight to 23.3 mumol/g wet weight over 7 days. After the period of seven days in severe hypoxia, the palmitate, octanoate and palmitoylcarnitine oxidation rates of mitochondrial suspensions were significantly reduced when the citric acid cycle was operative. No decrease in the fatty acid, fatty acyl-CoA or carnitine derivative oxidation was observed when only the beta oxidation system was studied. Mitochondria isolated from the heart or liver after seven days in severe hypoxia showed reduced respiratory control ratios, the decrease being from the normal 4.9 to 1.9 in the liver mitochondria using succinate as substrate. The reduction in respiratory control was mainly due to lowered State 3 respiration rates. Some reduction in the ratio was also observed in the fasting controls, from 5.8 to 3.4 with succinate. The respiratory control ratio could be partially normalized by the addition of albumin to the isolation medium for the liver mitochondria after severe hypoxia. Under these conditions, however, the State 4 respiration of the mitochondria from the hypoxic animals was higher than that for the controls.

Animals↗
PubMed1978

Metabolic adaptation to hypoxia. Redox state of the cellular free NAD pools, phosphorylation state of the adenylate system and the (Na+-K+)-stimulated ATP-ase in rat liver.

The effect of hypoxia (30 min 10% or 8% O2) on the phosphorylation state and redox state of the cytosol and mitochondria of rat liver were studied. Measurements were made both from normal animals and animals which had been exposed to the reduced partial pressure of oxygen (50.5 kPa or 40.8 kPa of air) for one or seven days. Cytostolic free NAD was reduced in the liver both in acute hypoxia and in hypoxia after one or seven days, i.e. the lactate/pyruvate and sn-glycerol-3-phosphate/dioxyacetonephosphate ratios increased markedly. A marked reduction in the mitochondrial free NAD pool occurred only in acute hypoxia and only a slight reduction was observed in animals kept at 40.8 kPa for one or seven days, as evaluated from the hepatic hydroxybutyrate/acetoacetate ratio. Liver ATP concentration decreased rapidly in acute hypoxia without any significant recovery during one or seven days at 40.8 kPa. The hepatic ATP/ADP X Pi ratio decreased significantly, with a simultaneous decrease in the total adenine nucleotide concentration. A tendency was observed for the ATP/ADP X Pi ratio to return to normal after seven days, i.e. the values in acute hypoxia were significantly smaller than those noted in hypoxia after seven days, demonstrating an adaptation of the energy metabolism during prolonged hypoxia. Hepatic (Na+-K+)-stimulated ATP-ase activity was not affected by hypoxia.

Acetates↗
PubMed1978

Hepatic triacylglycerol and fatty-acid biosynthesis during hypoxia in vivo.

Hepatic fatty acid biosynthesis and the activity of phosphatidate phosphatidate phosphohydrolase, the rate-limiting enzyme of triacylglycerol biosynthesis, were studied after hypoxic periods of 1 and 7 days under hypobaric conditions at 40.8 kPa. Phosphatidate phosphohydrolase activity increased 2-fold in the soluble fraction of the liver after one day at 40.8 kPa, but had returned to normal by 7 days. This was accompanied by a significant increase in liver triacylglycerol and sn-glycerol-3-phosphate. The phosphatidate phosphohydrolase activity increased continuously over 7 days in the pair-fed controls, probably due to the restriction on food. Measured as in vivo incorporation of 3H2O into lipids, the hepatic fatty acid synthesis rate increased somewhat in acute hypoxia, but returned to normal values during 7 days of hypoxia. Plasma free fatty acids increased markedly after 24 h in the fasting controls (90%) with a smaller increase in the hypoxic group (50%) due to peripheral lipolysis. Hepatic glycogen stores decreased in the hypoxic and fasting animals both after 1 and 7 days. It is concluded that hypoxia induces the accumulation of fat into the liver at least partly as a consequence of an increase in phosphatidate phosphohydrolase activity in the soluble fraction of the liver.

Animals↗
PubMed1977

Effect of hypoxia on mitochondrial mass and cytochrome concentrations in rat heart and liver during postnatal development.

Cytochrome concentrations of rat heart and liver mitochondria were measured postnatally from newborn animals to young adults. Mitochondrial cytochrome aa3 concentration increased shortly after birth in both tissues, this concentration being in a newborn animal 0.149 +/- 0.027 nmol/mg protein in liver and 0.333 +/- 0.082 nmol/mg protein in heart. The respective values from a two week old animal were 0.216 +/- 0.031 and 0.583 +/- 0.100. Postnatally cytochromes c+c1 and b increased markedly in the heart, but in the liver of newborn animals the cytochrome content was more close to the adult values. The amount of mitochondrial protein increased after birth, too. In a newborn animal the mitochondrial protein values were 39.7 +/- 3.6 mg/g wet weight in liver and 26.6 +/- 6.5 mg/g wet weight in heart. In adult animals the respective values were 71.5 +/- 4.8 and 80.7 +/- 13.1. The effect of postnatal hypoxia (10% O2, 24 h and 48 h) on liver and heart mitochondrial cytochrome concentration and protein values of newborn animals were investigated. During hypoxia the amount of mitochondrial protein remained about at the level of a newborn animal. The postnatal increase in the mitochondrial cytochrome concentration, which was smaller in the liver than in the heart, was also inhibited by hypoxia.

Age Factors↗