K. Vaali - Academia.edu (original) (raw)
Papers by K. Vaali
World Allergy Organization Journal, 2007
Food Chemistry, 2015
In Finland and France atopic children commonly react to seeds of oilseed rape and turnip rape in ... more In Finland and France atopic children commonly react to seeds of oilseed rape and turnip rape in skin prick tests (SPT) and open food challenges. These seeds are not as such in dietary use and therefore the routes of sensitization are unknown. Possible allergens were extracted from commercial cold-pressed and refined rapeseed oils and identified by gel-based tandem nanoflow liquid chromatography mass spectrometry (LC-MS/MS). Napin (a 2S albumin), earlier identified as a major allergen in the seeds of oilseed rape and turnip rape, and cruciferin (an 11S globulin), a new potential seed allergen, were detected in cold-pressed oils, but not in refined oils. Pooled sera from five children sensitized or allergic to oilseed rape and turnip rape seeds reacted to these proteins from cold-pressed oil preparations and individual sera from five children reacted to these proteins extracted from the seeds when examined with IgE immunoblotting. Hence cold-pressed rapeseed oil might be one possible route of sensitization for these allergens.
Journal of Allergy and Clinical Immunology, 2004
ABSTRACT
Journal of Allergy and Clinical Immunology, 2005
Background: Children with IgE-mediated allergy to foods frequently react to seeds of oilseed rape... more Background: Children with IgE-mediated allergy to foods frequently react to seeds of oilseed rape (Brassica napus ssp. oleifera) and turnip rape (Brassica rapa ssp. oleifera) in skin prick tests (SPTs). Sensitization pathways are not known. Objective: We identified possible major allergens in oilseed rape and turnip rape using sera from 72 atopic children (mean age, 3.3 years) with positive SPT responses to oilseed rape and turnip rape. Methods: Allergens from oilseed rape and turnip rape seed extracts were purified by using gel filtration and cation exchange chromatography and characterized by means of reversed-phase chromatography, N-terminal amino acid sequencing, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. IgE binding of sera from 72 children with positive SPT reactions to oilseed rape and turnip rape and 72 age-and sex-matched atopic control subjects with negative SPT responses were analyzed by means of IgE ELISA and immunoblotting. In vivo reactivity of the purified allergens was tested with SPTs in 6 children. Results: In IgE immunoblotting and IgE ELISA major reactivity was to a group of homologous, approximately 9.5to 14.5-kd proteins. These allergens were identified as 2S albumins, also known as napins, by means of N-terminal amino acid sequencing. In ELISA approximately 80% of the patients had IgE to purified napins from both plants. In SPTs purified napins caused positive reactions in all 6 children tested. Conclusions: This study shows that 2S albumins in oilseed rape and turnip rape are new potential food allergens. Further studies are needed to clarify the routes of exposure and mechanisms of sensitization. (J Allergy Clin Immunol 2006;117:426-32.)
World Allergy Organization Journal, 2007
Inflammation, 2001
In inflammatory bowel disease, increased production of prostaglandins by cyclooxygenase-2 (COX-2)... more In inflammatory bowel disease, increased production of prostaglandins by cyclooxygenase-2 (COX-2) contributes to bowel dysfunction, inflammatory edema, and hyperemia suggesting that inhibitors of COX-2 may have beneficial effect in gut inflammation. We compared the effects of nimesulide, a preferential COX-2 inhibitor, with those of indomethacin, acetylsalicylic acid (ASA), and dexamethasone in a 24-h model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in the rat. TNBS-induced colitis was associated with enhanced COX-2 expression in the gut and increased circulating concentrations of PGE2 metabolite (PGEM). Treatment with nimesulide (10 mg/kg), indomethacin (10 mg/kg), or dexamethasone (1 mg/kg) reduced plasma PGEM concentrations and edema in the inflamed bowel. In addition, nimesulide and dexamethasone treatments decreased neutrophil infiltration into the inflamed colon mucosa. ASA (10 mg/kg) did not have a significant effect on any of these measures of inflammation....
![Research paper thumbnail of Suppression of acute experimental colitis by a highly selective inducible nitric-oxide synthase inhibitor, N-[3-(aminomethyl)benzyl]acetamidine](https://attachments.academia-assets.com/53058527/thumbnails/1.jpg)
](The Journal of pharmacology and experimental therapeutics, 2001
High concentrations of nitric oxide (NO) produced by the inducible nitric-oxide synthase (iNOS) a... more High concentrations of nitric oxide (NO) produced by the inducible nitric-oxide synthase (iNOS) are associated with ulcerative inflammation and disease activity in colitis. Therefore, inhibition of iNOS serves as a novel experimental approach to treat gut inflammation. The aim of the present study was to investigate the effects of a novel highly selective iNOS inhibitor, N-[3-(aminomethyl)benzyl]acetamidine (1400W), as compared with a nonselective NOS inhibitor, N(G)-nitro-L-arginine-methyl-ester (L-NAME), in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis in the rat. Increased expression of iNOS protein and mRNA was found in acute TNBS-induced colitis along with neutrophil infiltration, inflammatory edema, and tissue damage. In a 24-h model of acute colitis, subcutaneous injections of 1400W (5 or 10 mg/kg t.i.d.) produced a 56 and 95% reduction in inflammatory edema formation, a 68 and 63% reduction in neutrophil infiltration (measured as myeloperoxidase activity), ...
European journal of pharmacology, Jan 18, 1998
The effects of interaction between the beta2-adrenoreceptor agonist, salbutamol, and the nitric o... more The effects of interaction between the beta2-adrenoreceptor agonist, salbutamol, and the nitric oxide donors, sodium nitroprusside and 3-morpholinosydnonimine (SIN-1), on guinea pig trachea contraction were studied. Cumulatively increased concentrations (0.1-10 nM) of salbutamol together with a single concentration of SNP (0.33 microM) or with SIN-1 (1 microM) showed significant (p < 0.001) synergy for the inhibition of 1 microM metacholine-induced contraction. Significant synergy (p < 0.05) was also found for the inhibition of this contraction by cumulatively increased concentrations (0.1-33 microM) of SNP and a single concentration (1 nM) of salbutamol. No synergistic effect was found on the 40 mM KC1-induced contraction. We suggest that the combination of NO donors with salbutamol has a synergistic effect on metacholine contraction.
The Journal of pharmacology and experimental therapeutics, 1998
The relaxing effects of the nitric oxide (NO) donors 1,2,3,4-oxatriazolium,3-(3-chloro-2-methylph... more The relaxing effects of the nitric oxide (NO) donors 1,2,3,4-oxatriazolium,3-(3-chloro-2-methylphenyl-5-[[(4-methoxyphe nyl) sulfonyl]amino]-,hydroxide inner salt (GEA 3268) 1,2,3,4-oxatriazolium,3-(3-chloro-2-methyphenyl-5-[methys ulfonyl)amino]- hydroxide inner salt (GEA 5145), 3-morpholinosydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP) were inhibited in vitro by iberiotoxin (IbTX) and charybdotoxin (ChTX), the two selective inhibitors of Ca(++)-activated K+ channels (KCa) in guinea pig trachea. When studied in cumulative concentrations in metacholine constriction, the relaxing effects of the NO donors were inhibited by at least 70% in the presence of the toxins, with the exception of SIN-1 in the presence of ChTX. The inhibitory effect of ChTX was less marked than that of IbTX. This suggests that the relaxing effects of the structurally different NO donors are mediated through KCa channels and that IbTX is more potent than ChTX. A selective inhibitor of soluble gua...
Life Sciences, 1998
Z&y Word: guinea pig trachea, smooth muscle relaxation, fenamates, flufenamic acid, tolfenamic ac... more Z&y Word: guinea pig trachea, smooth muscle relaxation, fenamates, flufenamic acid, tolfenamic acid, lemakalim, potassium channels PL-306
Scandinavian Journal of Immunology, 2012
Neurogastroenterology & Motility, 2012
Background When sensitized epicutaneously and challenged orally with ovalbumin, Balb/c mice devel... more Background When sensitized epicutaneously and challenged orally with ovalbumin, Balb/c mice develop allergen-induced diarrhea. As mast cells play important roles in diarrhea, we studied whether allergic diarrhea could be alleviated with imatinib mesylate. Methods Balb/c mice were sensitized and challenged with ovalbumin and treated orally with imatinib. Cytokine mRNA expressions were determined with quantitative RT-PCR and numbers of small intestinal mast cells determined by staining for chloroacetate esterase and mucosal mast cell protease-1. Immunofluorescence staining was used to assess the intestinal CCL1 expression. Key Results Ovalbumin-sensitized and challenged Balb/c mice developed diarrhea, which was associated with increased number of mast cells and expression of interleukin (IL)-4 and -13, and chemokines CCL1 and CCL17 in the small intestine. Treatment with imatinib reduced the incidence of diarrhea, inhibited the development of mastocytosis and jejunal mRNA expression of IL-13, CCL1, CCL17 and CCL22. Mast cell-deficient W/W -V mice, and surprisingly, also their mast cell-competent control (+/+) littermates failed to develop diarrhea as a response to ovalbumin. This strain-dependent difference was associated with the inability of +/+ and W/W -V mice to increase the number of intestinal mast cells and expression of IL-4, IL-13, CCL1 and CCL17 after ovalbumin challenge.
Marine Pollution Bulletin, 1998
Sediment cores were collected from five coastal wetlands in England, the Netherlands, and Poland,... more Sediment cores were collected from five coastal wetlands in England, the Netherlands, and Poland, and samples analysed for heavy metal concentrations. Depth profiles of metal concentrations were converted to time-based profiles, using vertical accretion rates obtained from 137Cs dating. Chronologies of metal concentrations from the two cores (high and low marsh) at each site showed good agreement, indicating that sediment
Marine Pollution Bulletin, 1998
Mercury concentrations in the hair and various tissues of the Saimaa ringed seal were monitored f... more Mercury concentrations in the hair and various tissues of the Saimaa ringed seal were monitored from 1980 to 1995. In the liver, muscle and kidney of weaned pups mercury concentrations dropped in the middle of the 1980s. In the natal hair and liver of young pups, however, no clear decrease was seen. In the natal hair and main fish prey species of the seals mercury concentration were highest in areas of humic water. Mercury concentration in the liver of adults has not changed significantly since 1981. Age of the seal is clearly correlated with mercury concentration in the liver. Shortage of selenium is assumed to be one reason for high concentrations of mercury in muscle. The mercury concentration in hair decreased markedly in an adult seal in captivity, after giving selenium. Based on these findings, one reason for the decrease in population density of the Saimaa seal in this century may have been mercury pollution.
Life Sciences, 1997
The role of K' channels in the relaxations induced by bradykinin, lemakalim, an activator of ATP-... more The role of K' channels in the relaxations induced by bradykinin, lemakalim, an activator of ATP-sensitive K' channels and sodium nitroprusside (SNP), a nitric oxide (NO) donor was examined in the isolated mouse trachea precontracted by methacholine (1 PM). 4aminopyridine (4-AP, 0.1-2 mM), an inhibitor of 4-AP sensitive delayed rectifier channels, did not alter relaxations induced by bradykinin, lemakalim or SNP. Glibenclamide and glipizide (1 O-33 PM), inhibitors of ATP-sensitive K' channels, inhibited relaxation to lemakalim without affecting responses to bradykinin and SNP. Charybdotoxin (10-l 00 r&I) and iberiotoxin (10-l 00 r&I), inhibitors of large conductance Ca2'-activated K' channels, failed to inhibit relaxation to bradykinin, lemakalim or SNP. Apamin (0.1-l PM), an inhibitor of small conductance Ca"activated K' channels, did not alter responses to bradykinin, lemakalim and SNP. The results implicate that the mechanism of relaxation induced by bradykinin and SNP is different from that of lemakalim. Relaxation of the isolated mouse trachea by lemakalim appears to be mediated by ATP-sensitive K' channels. Bradykinin and SNP induced relaxations are not mediated via Ca"activated K' channels. o 1997 Elsevier Science Inc.
Life Sciences, 1998
The inhibitory and relaxant effects of flufenamic and tolfenamic acids on guinea-pig isolated bro... more The inhibitory and relaxant effects of flufenamic and tolfenamic acids on guinea-pig isolated bronchus were compared with those of verapamil and indomethacin.
Journal of Pharmacy and Pharmacology, 1996
Endogenously released nitric oxide (NO) in airways might contribute to physiological bronchodilat... more Endogenously released nitric oxide (NO) in airways might contribute to physiological bronchodilation; induced production of NO might play a role in the pathogenesis of asthma, although it could also be a compensatory mechanism to other factors that cause bronchoconstriction or inflammation. To investigate the efficacy of NO donors on bronchial tone, the bronchorelaxing efficacies of NO donors, new experimental GEA compounds 3268 and 5145 (oxatriazole sulphonylamides) were compared with those of sodium nitroprusside and SIN-1 (3-morpholinosydnonimine) and to the standard B2-adrenergic agonist, salbutamol, in bronchi of guinea-pigs and rats in-vitro. Their relaxing effects were also studied in rat mesentery arteries to compare the selectivity for airways. The capacity of the NO donors to produce nitrites and nitrates was assayed by the Griess reaction.
Journal of Pharmacy and Pharmacology, 1996
The mechanism of the bronchospasmolytic effect of HOE 234 ((3S,4R)-3-hydroxy-2,2-dimethy1-4-(2-0~... more The mechanism of the bronchospasmolytic effect of HOE 234 ((3S,4R)-3-hydroxy-2,2-dimethy1-4-(2-0~0-1pyrrolidinyl)-6-phenylsulphonylchromane hemihydrate), a novel opener of ATP-sensitive potassium channels, has been studied by in-vitro testing in ring preparations of trachea and different parts of the principle bronchus of guinea-pigs, using methacholine, histamine and KCl as preconstrictors. The contribution of prostanoids was estimated in the presence and absence of indomethacin. Regional differences in the bronchodilatory effect of HOE 234 were compared with that of salbutamol.
Journal of Clinical Investigation, 1997
The role of nitric oxide in obliterative bronchiolitis development, i.e., chronic rejection, was ... more The role of nitric oxide in obliterative bronchiolitis development, i.e., chronic rejection, was investigated in the heterotopic rat tracheal allograft model. An increase in the intragraft inducible nitric oxide synthase (iNOS) mRNA and mononuclear inflammatory cell iNOS immunoreactivity was demonstrated during progressive loss of respiratory epithelium and airway occlusion in nontreated allografts compared to syngeneic grafts. In nontreated allografts, however, intragraft nitric oxide production was decreased, most likely because of loss of iNOS epithelial expression. Treatment with aminoguanidine, a preferential inhibitor of inducible nitric oxide synthase, was associated with enhanced proliferation of alpha-smooth muscle actin immunoreactive cells and the intensity of obliterative bronchiolitis early after transplantation. Aminoguanidine treatment did not affect iNOS mRNA synthesis or intragraft nitric oxide production, but decreased iNOS immunoreactivity in smooth muscle cells. Treatment with L-arginine, a precursor of nitric oxide, significantly reduced obliterative changes. L-arginine supplementation enhanced intragraft iNOS mRNA synthesis and iNOS immunoreactivity in capillary endothelial and smooth muscle cells as well as intragraft nitric oxide production. Immunohistochemical analysis of allografts showed that neither iNOS inhibition nor supplementation of the nitric oxide pathway affected the number of graft-infiltrating CD4+ and CD8+ T cells, ED1+ and ED3+ macrophages, immune activation with expression of IL-2R or MHC class II, or production of macrophage or Th1 cytokines. In contrast, L-arginine treatment was associated with increased staining for Th2 cytokines IL-4 and IL-10. In conclusion, this study demonstrates that nitric oxide has a protective role in obliterative bronchiolitis development in this model, and suggests that nitric oxide either directly or indirectly inhibits smooth muscle cell proliferation and modulates immune response towards Th2 cytokines.
World Allergy Organization Journal, 2007
Food Chemistry, 2015
In Finland and France atopic children commonly react to seeds of oilseed rape and turnip rape in ... more In Finland and France atopic children commonly react to seeds of oilseed rape and turnip rape in skin prick tests (SPT) and open food challenges. These seeds are not as such in dietary use and therefore the routes of sensitization are unknown. Possible allergens were extracted from commercial cold-pressed and refined rapeseed oils and identified by gel-based tandem nanoflow liquid chromatography mass spectrometry (LC-MS/MS). Napin (a 2S albumin), earlier identified as a major allergen in the seeds of oilseed rape and turnip rape, and cruciferin (an 11S globulin), a new potential seed allergen, were detected in cold-pressed oils, but not in refined oils. Pooled sera from five children sensitized or allergic to oilseed rape and turnip rape seeds reacted to these proteins from cold-pressed oil preparations and individual sera from five children reacted to these proteins extracted from the seeds when examined with IgE immunoblotting. Hence cold-pressed rapeseed oil might be one possible route of sensitization for these allergens.
Journal of Allergy and Clinical Immunology, 2004
ABSTRACT
Journal of Allergy and Clinical Immunology, 2005
Background: Children with IgE-mediated allergy to foods frequently react to seeds of oilseed rape... more Background: Children with IgE-mediated allergy to foods frequently react to seeds of oilseed rape (Brassica napus ssp. oleifera) and turnip rape (Brassica rapa ssp. oleifera) in skin prick tests (SPTs). Sensitization pathways are not known. Objective: We identified possible major allergens in oilseed rape and turnip rape using sera from 72 atopic children (mean age, 3.3 years) with positive SPT responses to oilseed rape and turnip rape. Methods: Allergens from oilseed rape and turnip rape seed extracts were purified by using gel filtration and cation exchange chromatography and characterized by means of reversed-phase chromatography, N-terminal amino acid sequencing, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. IgE binding of sera from 72 children with positive SPT reactions to oilseed rape and turnip rape and 72 age-and sex-matched atopic control subjects with negative SPT responses were analyzed by means of IgE ELISA and immunoblotting. In vivo reactivity of the purified allergens was tested with SPTs in 6 children. Results: In IgE immunoblotting and IgE ELISA major reactivity was to a group of homologous, approximately 9.5to 14.5-kd proteins. These allergens were identified as 2S albumins, also known as napins, by means of N-terminal amino acid sequencing. In ELISA approximately 80% of the patients had IgE to purified napins from both plants. In SPTs purified napins caused positive reactions in all 6 children tested. Conclusions: This study shows that 2S albumins in oilseed rape and turnip rape are new potential food allergens. Further studies are needed to clarify the routes of exposure and mechanisms of sensitization. (J Allergy Clin Immunol 2006;117:426-32.)
World Allergy Organization Journal, 2007
Inflammation, 2001
In inflammatory bowel disease, increased production of prostaglandins by cyclooxygenase-2 (COX-2)... more In inflammatory bowel disease, increased production of prostaglandins by cyclooxygenase-2 (COX-2) contributes to bowel dysfunction, inflammatory edema, and hyperemia suggesting that inhibitors of COX-2 may have beneficial effect in gut inflammation. We compared the effects of nimesulide, a preferential COX-2 inhibitor, with those of indomethacin, acetylsalicylic acid (ASA), and dexamethasone in a 24-h model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in the rat. TNBS-induced colitis was associated with enhanced COX-2 expression in the gut and increased circulating concentrations of PGE2 metabolite (PGEM). Treatment with nimesulide (10 mg/kg), indomethacin (10 mg/kg), or dexamethasone (1 mg/kg) reduced plasma PGEM concentrations and edema in the inflamed bowel. In addition, nimesulide and dexamethasone treatments decreased neutrophil infiltration into the inflamed colon mucosa. ASA (10 mg/kg) did not have a significant effect on any of these measures of inflammation....
The Journal of pharmacology and experimental therapeutics, 2001
High concentrations of nitric oxide (NO) produced by the inducible nitric-oxide synthase (iNOS) a... more High concentrations of nitric oxide (NO) produced by the inducible nitric-oxide synthase (iNOS) are associated with ulcerative inflammation and disease activity in colitis. Therefore, inhibition of iNOS serves as a novel experimental approach to treat gut inflammation. The aim of the present study was to investigate the effects of a novel highly selective iNOS inhibitor, N-[3-(aminomethyl)benzyl]acetamidine (1400W), as compared with a nonselective NOS inhibitor, N(G)-nitro-L-arginine-methyl-ester (L-NAME), in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis in the rat. Increased expression of iNOS protein and mRNA was found in acute TNBS-induced colitis along with neutrophil infiltration, inflammatory edema, and tissue damage. In a 24-h model of acute colitis, subcutaneous injections of 1400W (5 or 10 mg/kg t.i.d.) produced a 56 and 95% reduction in inflammatory edema formation, a 68 and 63% reduction in neutrophil infiltration (measured as myeloperoxidase activity), ...
European journal of pharmacology, Jan 18, 1998
The effects of interaction between the beta2-adrenoreceptor agonist, salbutamol, and the nitric o... more The effects of interaction between the beta2-adrenoreceptor agonist, salbutamol, and the nitric oxide donors, sodium nitroprusside and 3-morpholinosydnonimine (SIN-1), on guinea pig trachea contraction were studied. Cumulatively increased concentrations (0.1-10 nM) of salbutamol together with a single concentration of SNP (0.33 microM) or with SIN-1 (1 microM) showed significant (p < 0.001) synergy for the inhibition of 1 microM metacholine-induced contraction. Significant synergy (p < 0.05) was also found for the inhibition of this contraction by cumulatively increased concentrations (0.1-33 microM) of SNP and a single concentration (1 nM) of salbutamol. No synergistic effect was found on the 40 mM KC1-induced contraction. We suggest that the combination of NO donors with salbutamol has a synergistic effect on metacholine contraction.
The Journal of pharmacology and experimental therapeutics, 1998
The relaxing effects of the nitric oxide (NO) donors 1,2,3,4-oxatriazolium,3-(3-chloro-2-methylph... more The relaxing effects of the nitric oxide (NO) donors 1,2,3,4-oxatriazolium,3-(3-chloro-2-methylphenyl-5-[[(4-methoxyphe nyl) sulfonyl]amino]-,hydroxide inner salt (GEA 3268) 1,2,3,4-oxatriazolium,3-(3-chloro-2-methyphenyl-5-[methys ulfonyl)amino]- hydroxide inner salt (GEA 5145), 3-morpholinosydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP) were inhibited in vitro by iberiotoxin (IbTX) and charybdotoxin (ChTX), the two selective inhibitors of Ca(++)-activated K+ channels (KCa) in guinea pig trachea. When studied in cumulative concentrations in metacholine constriction, the relaxing effects of the NO donors were inhibited by at least 70% in the presence of the toxins, with the exception of SIN-1 in the presence of ChTX. The inhibitory effect of ChTX was less marked than that of IbTX. This suggests that the relaxing effects of the structurally different NO donors are mediated through KCa channels and that IbTX is more potent than ChTX. A selective inhibitor of soluble gua...
Life Sciences, 1998
Z&y Word: guinea pig trachea, smooth muscle relaxation, fenamates, flufenamic acid, tolfenamic ac... more Z&y Word: guinea pig trachea, smooth muscle relaxation, fenamates, flufenamic acid, tolfenamic acid, lemakalim, potassium channels PL-306
Scandinavian Journal of Immunology, 2012
Neurogastroenterology & Motility, 2012
Background When sensitized epicutaneously and challenged orally with ovalbumin, Balb/c mice devel... more Background When sensitized epicutaneously and challenged orally with ovalbumin, Balb/c mice develop allergen-induced diarrhea. As mast cells play important roles in diarrhea, we studied whether allergic diarrhea could be alleviated with imatinib mesylate. Methods Balb/c mice were sensitized and challenged with ovalbumin and treated orally with imatinib. Cytokine mRNA expressions were determined with quantitative RT-PCR and numbers of small intestinal mast cells determined by staining for chloroacetate esterase and mucosal mast cell protease-1. Immunofluorescence staining was used to assess the intestinal CCL1 expression. Key Results Ovalbumin-sensitized and challenged Balb/c mice developed diarrhea, which was associated with increased number of mast cells and expression of interleukin (IL)-4 and -13, and chemokines CCL1 and CCL17 in the small intestine. Treatment with imatinib reduced the incidence of diarrhea, inhibited the development of mastocytosis and jejunal mRNA expression of IL-13, CCL1, CCL17 and CCL22. Mast cell-deficient W/W -V mice, and surprisingly, also their mast cell-competent control (+/+) littermates failed to develop diarrhea as a response to ovalbumin. This strain-dependent difference was associated with the inability of +/+ and W/W -V mice to increase the number of intestinal mast cells and expression of IL-4, IL-13, CCL1 and CCL17 after ovalbumin challenge.
Marine Pollution Bulletin, 1998
Sediment cores were collected from five coastal wetlands in England, the Netherlands, and Poland,... more Sediment cores were collected from five coastal wetlands in England, the Netherlands, and Poland, and samples analysed for heavy metal concentrations. Depth profiles of metal concentrations were converted to time-based profiles, using vertical accretion rates obtained from 137Cs dating. Chronologies of metal concentrations from the two cores (high and low marsh) at each site showed good agreement, indicating that sediment
Marine Pollution Bulletin, 1998
Mercury concentrations in the hair and various tissues of the Saimaa ringed seal were monitored f... more Mercury concentrations in the hair and various tissues of the Saimaa ringed seal were monitored from 1980 to 1995. In the liver, muscle and kidney of weaned pups mercury concentrations dropped in the middle of the 1980s. In the natal hair and liver of young pups, however, no clear decrease was seen. In the natal hair and main fish prey species of the seals mercury concentration were highest in areas of humic water. Mercury concentration in the liver of adults has not changed significantly since 1981. Age of the seal is clearly correlated with mercury concentration in the liver. Shortage of selenium is assumed to be one reason for high concentrations of mercury in muscle. The mercury concentration in hair decreased markedly in an adult seal in captivity, after giving selenium. Based on these findings, one reason for the decrease in population density of the Saimaa seal in this century may have been mercury pollution.
Life Sciences, 1997
The role of K' channels in the relaxations induced by bradykinin, lemakalim, an activator of ATP-... more The role of K' channels in the relaxations induced by bradykinin, lemakalim, an activator of ATP-sensitive K' channels and sodium nitroprusside (SNP), a nitric oxide (NO) donor was examined in the isolated mouse trachea precontracted by methacholine (1 PM). 4aminopyridine (4-AP, 0.1-2 mM), an inhibitor of 4-AP sensitive delayed rectifier channels, did not alter relaxations induced by bradykinin, lemakalim or SNP. Glibenclamide and glipizide (1 O-33 PM), inhibitors of ATP-sensitive K' channels, inhibited relaxation to lemakalim without affecting responses to bradykinin and SNP. Charybdotoxin (10-l 00 r&I) and iberiotoxin (10-l 00 r&I), inhibitors of large conductance Ca2'-activated K' channels, failed to inhibit relaxation to bradykinin, lemakalim or SNP. Apamin (0.1-l PM), an inhibitor of small conductance Ca"activated K' channels, did not alter responses to bradykinin, lemakalim and SNP. The results implicate that the mechanism of relaxation induced by bradykinin and SNP is different from that of lemakalim. Relaxation of the isolated mouse trachea by lemakalim appears to be mediated by ATP-sensitive K' channels. Bradykinin and SNP induced relaxations are not mediated via Ca"activated K' channels. o 1997 Elsevier Science Inc.
Life Sciences, 1998
The inhibitory and relaxant effects of flufenamic and tolfenamic acids on guinea-pig isolated bro... more The inhibitory and relaxant effects of flufenamic and tolfenamic acids on guinea-pig isolated bronchus were compared with those of verapamil and indomethacin.
Journal of Pharmacy and Pharmacology, 1996
Endogenously released nitric oxide (NO) in airways might contribute to physiological bronchodilat... more Endogenously released nitric oxide (NO) in airways might contribute to physiological bronchodilation; induced production of NO might play a role in the pathogenesis of asthma, although it could also be a compensatory mechanism to other factors that cause bronchoconstriction or inflammation. To investigate the efficacy of NO donors on bronchial tone, the bronchorelaxing efficacies of NO donors, new experimental GEA compounds 3268 and 5145 (oxatriazole sulphonylamides) were compared with those of sodium nitroprusside and SIN-1 (3-morpholinosydnonimine) and to the standard B2-adrenergic agonist, salbutamol, in bronchi of guinea-pigs and rats in-vitro. Their relaxing effects were also studied in rat mesentery arteries to compare the selectivity for airways. The capacity of the NO donors to produce nitrites and nitrates was assayed by the Griess reaction.
Journal of Pharmacy and Pharmacology, 1996
The mechanism of the bronchospasmolytic effect of HOE 234 ((3S,4R)-3-hydroxy-2,2-dimethy1-4-(2-0~... more The mechanism of the bronchospasmolytic effect of HOE 234 ((3S,4R)-3-hydroxy-2,2-dimethy1-4-(2-0~0-1pyrrolidinyl)-6-phenylsulphonylchromane hemihydrate), a novel opener of ATP-sensitive potassium channels, has been studied by in-vitro testing in ring preparations of trachea and different parts of the principle bronchus of guinea-pigs, using methacholine, histamine and KCl as preconstrictors. The contribution of prostanoids was estimated in the presence and absence of indomethacin. Regional differences in the bronchodilatory effect of HOE 234 were compared with that of salbutamol.
Journal of Clinical Investigation, 1997
The role of nitric oxide in obliterative bronchiolitis development, i.e., chronic rejection, was ... more The role of nitric oxide in obliterative bronchiolitis development, i.e., chronic rejection, was investigated in the heterotopic rat tracheal allograft model. An increase in the intragraft inducible nitric oxide synthase (iNOS) mRNA and mononuclear inflammatory cell iNOS immunoreactivity was demonstrated during progressive loss of respiratory epithelium and airway occlusion in nontreated allografts compared to syngeneic grafts. In nontreated allografts, however, intragraft nitric oxide production was decreased, most likely because of loss of iNOS epithelial expression. Treatment with aminoguanidine, a preferential inhibitor of inducible nitric oxide synthase, was associated with enhanced proliferation of alpha-smooth muscle actin immunoreactive cells and the intensity of obliterative bronchiolitis early after transplantation. Aminoguanidine treatment did not affect iNOS mRNA synthesis or intragraft nitric oxide production, but decreased iNOS immunoreactivity in smooth muscle cells. Treatment with L-arginine, a precursor of nitric oxide, significantly reduced obliterative changes. L-arginine supplementation enhanced intragraft iNOS mRNA synthesis and iNOS immunoreactivity in capillary endothelial and smooth muscle cells as well as intragraft nitric oxide production. Immunohistochemical analysis of allografts showed that neither iNOS inhibition nor supplementation of the nitric oxide pathway affected the number of graft-infiltrating CD4+ and CD8+ T cells, ED1+ and ED3+ macrophages, immune activation with expression of IL-2R or MHC class II, or production of macrophage or Th1 cytokines. In contrast, L-arginine treatment was associated with increased staining for Th2 cytokines IL-4 and IL-10. In conclusion, this study demonstrates that nitric oxide has a protective role in obliterative bronchiolitis development in this model, and suggests that nitric oxide either directly or indirectly inhibits smooth muscle cell proliferation and modulates immune response towards Th2 cytokines.