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Biomedical subjects

K Savolainen

Publications and source records attributed to K Savolainen.

At least 19 recordsLinked to original sources
PubMed1997

Comparison of cytotoxicity of man-made vitreous fibres.

The purpose of the study was to compare the cytotoxicity of man-made vitreous fibres (MMVFs): four refractory ceramic fibres (RCFs 1-4), two glasswool fibres (MMVF 10 and 11), a rockwool fibre (MMVF 21) and a slagwool fibre (MMVF 22). The ability of the fibres to induce haemolysis in sheep erythrocytes, to release lactate dehydrogenase (LDH) from rat alveolar macrophages (AM) and to increase the production of reactive oxygen metabolites (ROMs) in human polymorphonuclear leukocytes (PML) was studied. To assess the relative cytotoxicity of MMVFs, their toxicity was compared with that induced by quartz, chrysotile or titanium dioxide. MMVFs induced a modest, but dose-dependent, increase of haemolysis at doses of 0.5, 2.5 and 5.0 mg ml-1. The amount of haemolysis and LDH release induced by MMVFs was generally similar to that induced by titanium dioxide. Glasswool fibre MMVF 10 induced less LDH release from rat AM than rockwool MMVF 21 or slagwool MMVF 22 fibres, whereas glasswool fibre MMVF 11 induced less LDH release than slagwool fibre MMVF 22 (P < 0.05). All fibres also dose-dependently increased the production of ROMs at doses between 25 and 500 micrograms ml-1. The shapes of the time-courses of MMVF-induced production of ROMs suggest that the mechanisms whereby the different fibres induce ROM production may exhibit similar features. There are clear-cut differences in the potency of various MMVFs to induce cytotoxicity and oxidative burst. The present results also emphasize the importance of using several measures of toxicity when assessing the biological activity of various fibres in vitro.

Analysis of Variance↗
PubMed1996

Purification and characterisation of a plasmin-sensitive surface protein of Staphylococcus aureus.

Certain methicillin-resistant Staphylococcus aureus strains contain a 230-kDa cell-wall protein which is not present on the surface of other staphylococci. The presence of this 230-kDa protein is associated with a negative test result in commercial assays designed to detect fibrinogen-binding proteins and/or protein A on the staphylococcal surface. We have purified and partially characterised the 230-kDa protein from a lysostaphin digest of a non-agglutinating methicillin-resistant S. aureus strain. Partial amino acid sequence data obtained from the purified protein did not reveal any significant similarities to known proteins which indicates that the protein is novel. The 230-kDa protein was very sensitive to proteolysis; soluble plasmin, or plasmin formed on the bacterial-cell surface, rapidly degraded the 230-kDa protein to a 175-kDa form. The finding that the 230-kDa protein bound to lectins allowed its purification by affinity chromatography on immobilised wheat germ agglutinin. Furthermore, the degradation of the 230-kDa protein was associated with an increased adherence of non-agglutinating methicillin-resistant S. aureus cells to solid-phase fibronectin, fibrinogen or IgG.

Agglutination↗
PubMed1996

Acute effects of 1,1,1-trichloroethane inhalation on the human central nervous system.

The object of this study was to examine the immediate nervous effects of variable 1,1,1-trichloroethane (TCE) exposure combined with physical exercise. The effects on the quantitative electroencephalography (EEG), visual evoked potentials (VEP) and body sway were analyzed. Nine male volunteers were exposed to either a stable or a fluctuating exposure pattern with the same time-weighted average concentration of 200 ppm (8.1 mumol/l). In both cases, the subjects engaged in physical exercise during the exposures. Exercise alone induced an increase in the dominant alpha frequency in the EEG and, after an initial drop, an increase in the alpha percentage with a concomitant decrease in theta, whereas delta and beta bands remained unaffected. By contrast, exposure to TCI and exercise did not affect the alpha, theta or delta activities but induced changes in beta during the morning recordings at peak exposure to TCE. The body sway tended to decrease slightly during the fluctuating TCE exposure, and the later peaks in VEPs showed slight prolongations. Overall, no deleterious effects of exposure were noted.

Air Pollutants, Occupational↗
PubMed1996

Different effects of three bisphosphonates on nitric oxide production by RAW 264 macrophage-like cells in vitro.

The macrophage-suppressive properties of three bisphosphonates were evaluated by studying their effect on nitric oxide (NO) production by activated RAW 264 macrophage-like cells. The cells were activated with 10 micrograms/ml of lipopolysaccharide, and NO was determined as nitrite in the cell culture supernatant. The effect of the drugs on inducible NO synthase was determined by Western blot analysis. As free drugs, clodronate and pamidronate inhibited NO secretion in a dose-dependent manner, whereas alendronate had no effect. Liposome encapsulation enhanced the effect of clodronate by a factor of 7, but the potency of pamidronate weakened slightly when encapsulated in liposomes. The inducible NO synthase expression inside the cells was also decreased by liposomal clodronate. In contrast to pamidronate, clodronate could affect the NO secretion when given to the cells simultaneously with lipopolysaccharide, and the inhibitory action was still seen when the drug was added 2 h after lipopolysaccharide induction. The viability of the cells was not affected by free or liposomal clodronate, whereas pamidronate showed considerable cytotoxicity. This study shows the different actions of these three bisphosphonates on NO production by macrophages and suggests that liposomal clodronate is the most promising bisphosphonate as an anti-inflammatory agent, whereas aminobisphosphonates do not possess anti-inflammatory properties.

Alendronate↗
PubMed1995

Interactions of cis-fatty acids and their anilides with formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate and dioctanoyl-s,n-glycerol in human leukocytes.

Aniline-denaturated rape-seed food oils that contained anilides of linoleic and oleic acids caused a poisoning epidemic, known as Toxic Oil Syndrome, in Spain in 1981. Toxic Oil Syndrome affected mainly the lungs and the immune system of exposed individuals. Linoleic and oleic acids, and linoleic and oleic anilides increased the production of reactive oxygen metabolites in human polymorphonuclear leukocytes. Both cis-fatty acids inhibited a chemotactic peptide-, fMLP-induced production of reactive oxygen metabolites without affecting fMLP-induced elevation of intracellular calcium levels. Linoleic acid anilide slightly amplified fMLP-induced respiratory burst, whereas oleic acid anilide was without an effect. However, both fatty acid anilides decreased fMLP-induced elevation of levels of free intracellular calcium. Moreover, both cis-fatty acids and their anilides inhibited phorbol myristate acetate (PMA)- and dioctanoyl-s,n-glycerol (DiC8)-induced production of reactive oxygen metabolites. Thus, both cis-fatty acids and their anilides inhibited agonist-stimulated production of reactive oxygen metabolites; this is most likely due to interactions with cell signalling events. These results suggest that both linoleic and oleic acids and their anilides may inhibit immunological responses of leukocytes.

Analysis of Variance↗
PubMed1995

The effect of fiber length on the dissolution by macrophages of rockwool and glasswool fibers.

The effect of fiber length on the dissolution of experimental rockwool and commercial glasswood fibers in rat alveolar macrophage (AM) culture and in mere culture medium was studied. The ultrastructure of macrophages after their exposure to fibers and the suitability of macrophage-type cell line P388D1 culture in dissolution studies were also explored. The fiber samples included short (ground) and long (untreated) rockwool and glasswool fibers. The fibers were incubated in rat AM cultures, in P388D1 culture, or in mere culture medium for 4 or 8 days. The dissolution of the fibers was determined by measuring the amounts of silicon (Si), iron (Fe), and aluminum (Al) in the medium. There were no differences in the diameter of the fibers, but a clear difference existed in the length of the short and long fibers. The dissolution of Si, Fe, and Al was more pronounced from experimental rockwool than from commercial glasswool fibers. The dissolution of Si was always greater in mere culture medium than in rat AM culture. Moreover, the dissolution of Si was greater from the long fibers than from the short ones. On the contrary, the dissolution of Fe and Al in AM culture exceeded that in mere culture medium. The dissolution of Si, Fe, and Al from both fibers in P388D1 culture was similar to their dissolution in rat AM culture. The fibers were also effectively phagocytized by the macrophages. The present results together suggest that the intracellular and the extracellular dissolutions of man-made vitreous fibers differ from each other.

Aluminum↗
PubMed1995

The effect of free gallium and gallium in liposomes on cytokine and nitric oxide secretion from macrophage-like cells in vitro.

The aim of this study was to evaluate the effect of gallium nitrate, gallium-nitrilotriacetate (NTA) complex, and liposomal gallium-NTA on IL-6, TNF alpha, and nitric oxide (NO) release from activated macrophages. In addition, the expression of the inducible nitric oxide synthase (iNOS) was determined. Gallium inhibited dose-dependently the secretion of IL-6, TNF alpha, and NO from the LPS-induced macrophage-like RAW 264 cells. Encapsulation of gallium in negatively charged DSPG-liposomes increased its potency 10-50 times and 7-11 times compared to free gallium nitrate and gallium-NTA, respectively. Neither non-loaded liposomes nor NTA alone inhibited cytokine or NO secretion, demonstrating that the observed effects originated from gallium. Liposomal gallium-NTA inhibited the expression of iNOS by the macrophages, while other formulations of gallium had no effect. Thus, gallium, when delivered properly, suppresses macrophage functions by inhibiting the release of inflammatory mediators from the cells.

Animals↗
PubMed1994

Dithiocarbamates.

Explore the source record for details and available documents.

Agricultural Workers' Diseases↗
PubMed1994

TCDD decreases brain inositol concentrations in the rat.

A single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduced significantly brain regional inositol levels in both the most TCDD-susceptible (Long-Evans; LD50 9.8 micrograms/kg) and the most TCDD-resistant (Han/Wistar; LD50 > 7200 micrograms/kg) rat strain. The decrease emerged earlier in Long-Evans rats but was similar in magnitude at 8 days in both strains. There were some inconsistent and largely dose-independent changes in inositol-1- and inositol-4-monophosphate concentrations at 2 days. On day 8, a tendency towards reduced levels was seen especially in H/W rats. We conclude that TCDD reduces brain inositol levels presumably by inhibiting its synthesis by way of substrate deficit (hypoglycemia), but this effect does not appear to be causally related to the lethal action of TCDD.

Analysis of Variance↗
PubMed1994

Two-site enzyme immunoassay for measuring intact human osteocalcin in serum.

We developed a sensitive two-site sandwich ELISA for quantitative analysis of human osteocalcin in serum or plasma. Our method is based on two different highly specific antibodies recognizing epitopes at different ends of the protein so that only intact osteocalcin is detected. The method is fast (total analysis time less than 6 h/96 wells), precise (intraassay variation less than 2.3% at four different levels; n = 10, and interassay variation less than 2.5%, n = 5, respectively), and accurate, with a mean recovery of 105%. The detection limit in serum is approximately 0.1 micrograms/liter. The mean concentration of osteocalcin in normal serum with this assay is 3.3 micrograms/liter (SD 3.7 micrograms/liter; range 0.1-13.1 micrograms/liter; n = 41), and the reference range is 0.28-10.1 micrograms/liter (10 and 90% confidence limits). The method shows a reasonable positive linear correlation with other osteocalcin assays (Incstar, r = 0.55, p < 0.05, n = 13; Henning Oscatest, r = 0.52, p < 0.005, n = 34). A good correlation (r = 0.70, p < 0.001) between individual osteocalcin and bone-specific alkaline phosphatase serum concentrations was observed in normal subjects. We found a low or undetectable concentration of intact osteocalcin in serum of all four of our patients with acute primary hyperparathyroidism, and in all five patients with hypocalcemic secondary hyperparathyroidism, which suggests that PTH effectively inhibited the synthesis of osteocalcin in osteoblasts. The serum concentration of intact osteocalcin was elevated in two of three patients with chronic primary hyperparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Scanning electron microscopic study on the changes in the cell surface morphology of rat alveolar macrophages after their exposure to man-made vitreous fibers.

The purpose of the present study was to investigate the morphological changes in the surface of rat alveolar macrophages (AM) after their exposure to man-made vitreous fibers (MMVF). Also the ability of rat AM to phagocytize respirable-sized MMVF was studied. The study was carried out by exposing rat AMs in a temporal fashion, for from 30 min to 96 hr, to the fibers in vitro. Scanning electron microscopy (SEM) was used to demonstrate the morphological changes and the phagocytosis of MMVF by rat AMs. Before exposure, the cells had continuous membranes with a variety of small surface features. The phagocytosis of MMVF by AMs started within 30 min after the exposure and increased as a function of time. Also the formation of prominent rufflings and blebs increased by the time. Short fibers, less than 20 microns in length, were usually phagocytized by a single AM, whereas two or more AMs usually phagocytized longer fibers. The cells produced extensions which fasten them to the fibers or to other cells to form clumps or clusters of cells and fibers, each AM engulfing a part of a fiber. Over 70% of the exposed cells were viable and still active after 96 hr of exposure. This finding suggests that the MMVF were not acutely toxic to the rat AMs in vitro. The results also reveal that the surface morphology of the AMs changed slowly during exposure of MMVF and that the cells actively phagocytized MMVF even 96 hr after the beginning of the exposure.

Animals↗
PubMed1994

Rapid detection of methicillin-resistant Staphylococcus aureus strains not identified by slide agglutination tests.

Seventy-nine methicillin-resistant Staphylococcus aureus (MRSA) strains, isolated during 1980 to 1990, were classified as MRSA Aggl- (14 strains) and MRSA Aggl+ (65 strains) strains on the basis of test results in slide agglutination assays designed to detect fibrinogen-binding protein (clumping factor) and protein A on the staphylococcal surface. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that lysostaphin digests of MRSA Aggl- strains contained a high-molecular-weight protein which was not detected in digests of MRSA Aggl+ strains. Immunization of rabbits with an MRSA Aggl- strain produced an antiserum which agglutinated all MRSA Aggl- strains and also 64 of 65 MRSA Aggl+ strains. Only 1 of 68 coagulase-negative staphylococci showed agglutination in this assay. The anti-MRSA Aggl- antiserum reacted mainly with a 230-kDa staphylococcal surface protein but also with a 175-kDa protein, probably formed by proteolysis of the former and a few slightly smaller proteins. These could not be immunologically detected in lysostaphin digests of MRSA Aggl+ strains. Purified antibodies reacting with the 230-kDa protein agglutinated all MRSA Aggl- strains, indicating that the protein is located on the surfaces of staphylococci. The results suggest a tentative role for the 230-kDa protein or its fragments as a novel target to develop more efficient rapid identification methods for S. aureus, including MRSA.

Agglutination Tests↗
PubMed1994

Dissolution of man-made vitreous fibers in rat alveolar macrophage culture and Gamble's saline solution: influence of different media and chemical composition of the fibers.

The effect of different chemical compositions of man-made vitreous fibers (MMVF) on their dissolution by alveolar macrophages (AM) in culture and in Gamble's solution was studied. The fibers were exposed to cultured rat AMs, culture medium alone; or Gamble's saline solution for 2, 4, or 8 days. The dissolution of the fibers was studied by measuring the amount of silicon (Si), iron (Fe), and aluminum (Al) in each medium. The AMs in culture dissolved Fe and Al from the fibers but the dissolution of Si was more marked in the cell culture medium without cells and in the Gamble's solution. The dissolution of Si, Fe, and Al was different for different fibers, and increased as a function of time. The Fe and Al content of the fibers correlated negatively with the dissolution of Si by AMs from the MMVF, i.e., when the content of Fe and Al of the fibers increased the dissolution of Si decreased. These results suggest that the chemical composition of MMVFs has a marked effect on their dissolution. AMs seem to affect the dissolution of Fe and Al from the fibers. This suggests that in vitro models with cells in the media rather than only culture media or saline solutions would be preferable in dissolution studies of MMVFs.

Animals↗
PubMed1994

Phosphoinositide second messengers in cholinergic excitotoxicity.

Acetylcholine (ACh) is a powerful excitotoxic neurotransmitter in the brain. By stimulating Ca(2+)-mobilizing receptors, ACh, through G-protein(s), stimulates phospholipase C and causes the hydrolysis of a membrane phospholipid, phosphatidylinositol-4,5-bisphosphate to two second messengers, inositol-1,4,5-trisphosphate (ins-(1,4,5)-P3), and diacylglycerol. Ins-(1,4,5)-P3 is important in cholinergic neuronal stimulation, and injury. Cholinergic agonists cause tonic-clonic convulsions which may be either transient or persistent. Even short-term cholinergic convulsions may be associated with neuronal injury, especially in the basal forebrain and the hippocampus. Cholinergic-induced convulsions also elevate levels of brain Ca2+ which precede neuronal injury. Female sex and senescence increase the sensitivity of rats to cholinergic excitotoxicity. Even if cholinergic-induced brain phosphoinositide signalling is likely to trigger cholinergic excitotoxicity, several other processes may be involved in the ensuing neuronal injury. Once initiated, cholinergic convulsions cannot be stopped with cholinergic antagonists such as atropine even though they are effective when given prior to a cholinergic agonist. However, glutaminergic antagonists, and GABAergic agonists, are effective in the attenuation of ongoing cholinergic status epilepticus. Cholinergic brain stimulation may be, in fact, under a partial control of brain GABAergic tonus, but also cause the release of glutamate. Glutamate stimulates inositol lipid signalling in several neuronal cells and, therefore, underlines the significance of inositol lipid signalling in cholinergic-induced excitotoxicity. Moreover, the anatomical distribution of cholinergic brain damage correlates well with that of glutaminergic neurons. Furthermore, glutamate increases neuronal oxidative stress, i.e. it increases the levels of free intracellular calcium, the production of reactive oxygen species, and causes the depletion of neuronal glutathione. The role of excitatory amino acids as common mediators of cholinergic excitotoxicity may offer new insights into the neurotoxic consequences of cholinergic neuronal stimulation.

Acetylcholine↗
PubMed1994

Enzymatic diagnosis of aspartylglycosaminuria by fluorometric assay of glycosylasparaginase in serum, plasma, or lymphocytes.

Serum, plasma, and lymphocytes from aspartylglycosaminuria (AGU) patients and carriers and from normal controls were incubated with a fluorescent glycosylasparaginase substrate, L-aspartic acid beta-(7-amido-4-methylcoumarin), and the release of 7-amino-4-methylcoumarin was measured fluorometrically after incubation for 1-4 h. The mean glycosylasparaginase (EC 3.5.1.26) activity in normal serum, plasma, and lymphocytes was 20.2 (SD 5.0) mU/L (n = 24), 17.5 (SD 5.0) mU/L (n = 24), and 242 (SD 108) mU/g protein (n = 17), respectively. The corresponding values in the Finnish AGU patients were 0.7 (SD 0.4) mU/L (n = 10), 0.3 (SD 0.3) mU/L (n = 10), and 6.0 (SD 4.6) mU/g protein (n = 7). No overlapping values were obtained between the AGU patients and the carriers in any of the samples, but the values between the carriers and controls were overlapping in 28 of 29 serum, 22 of 29 plasma, and 4 of 21 lymphocyte samples. Thus, the fluorometric glycosylasparaginase assay in various blood samples allows specific detection of the enzyme defect in AGU, but cannot be used for reliable detection of carriers of the disease.

Acetylglucosamine↗