| 1. |
- Bergdahl, Ingvar A., et al.
(författare)
-
Lead binding to delta-aminolevulinic acid dehydratase (ALAD) in human erythrocytes
- 1997
-
Ingår i: Basic and Clinical Pharmacology and Toxicology. - : Wiley. - 0901-9928. ; 81:4, s. 153-158
-
Tidskriftsartikel (refereegranskat)abstract
- Over 99% of the lead present in blood is usually found in erythrocytes. To investigate the nature of this selective accumulation of lead in erythrocytes, the specific binding of lead to proteins in human erythrocytes was studied using liquid chromatography coupled to inductively coupled plasma mass spectrometry (LC-ICP-MS). The principal lead-binding protein had a mass of approximately 240 kDa, and adsorption to specific antibodies showed that protein was delta-aminolevulinic acid dehydratase (ALAD). Thus, the previous notion that lead in erythrocytes was bound primarily to haemoglobin has to be revised. Furthermore, in lead-exposed workers, the percentage of lead bound to ALAD was influenced by a common polymorphism in the ALAD gene. Specifically, in seven carriers of the ALAD2 allele, 84% of the protein-bound lead recovered was bound to ALAD compared to 81% in seven homozygotes for the ALAD1 allele whose erythrocytes were matched for blood-lead concentration. The small difference was statistically significant in Wilcoxon matched-pairs signed-rank test (P = 0.03). No ALAD allele-specific difference in ALAD-bound lead was found among 20 unexposed controls. Perhaps the difference in ALAD-bound lead can provide an explanation for the previously reported finding of higher blood-lead levels among carriers of the ALAD2 allele than among ALAD1 homozygotes in lead-exposed populations.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Johansson, Maria, et al.
(författare)
-
Structure-activity relationship for inhibition of CYP11B1-dependent glucocorticoid synthesis in Y1 cells by aryl methyl sulfones
- 1998
-
Ingår i: Pharmacology and Toxicology. - : Wiley. - 0901-9928 .- 1600-0773. ; 83:5, s. 225-230
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of xenobiotics on CYP11B1-dependent corticosterone synthesis (11 beta-hydroxylase) in mouse adrenocortical Y1 cells were studied. 3-Methylsulfonyl-2,2-bis(4-chlorophenyl)-1,1-dichloroethene (MeSO2-DDE) and some methylsulfonyl polychlorinated biphenyls (MeSO2-PCB) inhibited the corticosterone synthesis, whereas PCBs or DDE did not. This indicates a crucial role of the methyl sulfone group for this inhibitory effect. Kinetic analyses of MeSO2-DDE and the two most potent MeSO2-PCBs were conducted using Lineweaver-Burk double-reciprocal plots. The data showed a competitive inhibition of CYP11B1 by the compounds, with apparent inhibitory constants (Ki) of 1.6, 4.6, and 6.7 microM for MeSO2-DDE, 4-MeSO2-2,3,6,4'-tetrachlorobiphenyl, and 4-MeSO2-2,3,6,3',4'-pentachlorobiphenyl, respectively. For comparison, the substrate K(m) was 3.5 microM in the cells, and metyrapone and ketoconazole had apparent Ki-values of 0.8 and 0.04 microM, respectively. In contrast to all previously known inhibitors of CYP11B1, the aryl methyl sulfones are the first examples of CYP11B1 inhibitors not being heterocyclic amines or steroids. The aryl methyl sulfones are widespread environmental pollutants and their inhibition of CYP11B1 constitutes another potential mechanism for endocrine disruption. Their influence on the synthesis of adrenocortical hormones thus merits further interest.
|
|
| 10. |
- Luurila, S., et al.
(författare)
-
Pharmacokinetics of bisphosphonates in rabbits
- 1999
-
Ingår i: Pharmacology and Toxicology. - : Blackwell Munksgaard. - 0901-9928 .- 1600-0773. ; 84:1, s. 24-28
-
Tidskriftsartikel (refereegranskat)abstract
- Clodronate, pamidronate and etidronate are commonly used bisphosphonates, which accumulate extensively in arteries and some other tissues. We compared their pharmacokinetics in rabbits with those of tiludronate, the drug newly introduced to clinical use. The 14C-labelled drugs were given intravenously and plasma drug levels were monitored for up to 24 hr. The dose-related plasma concentrations of tiludronate and etidronate were clearly higher and decreased more slowly than those of clodronate and pamidronate (P<0.001). Already at 5 min., the concentrations of tiludronate and etidronate were higher than those of clodronate and pamidronate (P=0.016). At 24 hr, plasma concentration of tiludronate was 12 ± 6.6%, of etidronate 18 ± 2.5%, of clodronate 0.8 ± 0.2%, and of pamidronate 1.4 ± 0.4% of the dose per body weight. With the same dose (25 mg/kg), absolute AUC(0-24hr) for tiludronate and etidronate was 9-11 times larger than for clodronate. AUC(0-24hr) for pamidronate (2.5 mg/kg) was 11% of that for clodronate. Plasma clearance of tiludronate and etidronate was 9- 15 times slower than that of clodronate and pamidronate. At 24 hr, the mean tissue-to-plasma ratio of tiludronate for aorta was 1.2-1.6. For bone, spleen, liver and kidneys the ratio varied from 5.4 to 52.6. The results suggest that 1) tiludronate and etidronate are removed from plasma much slower than clodronate and pamidronate, and 2) the potential of filudronate to concentrate in arteries and bone is generally smaller than previously found with the other bisphosphonates.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- BAGER, Y, et al.
(författare)
-
Interaction of 3,4,5,3',4'-pentachlorobiphenyl and 2,4,5,2',4',5'-hexachlorobiphenyl in promotion of altered hepatic foci in rats
- 1995
-
Ingår i: Pharmacology & toxicology. - : Wiley. - 0901-9928 .- 1600-0773. ; 77:2, s. 149-154
-
Tidskriftsartikel (refereegranskat)
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- FREDHOLM, BB
(författare)
-
Purinoceptors in the nervous system
- 1995
-
Ingår i: Pharmacology & toxicology. - : Wiley. - 0901-9928 .- 1600-0773. ; 76:4, s. 228-239
-
Tidskriftsartikel (refereegranskat)
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
- Lind, Y, et al.
(författare)
-
The influence of humic substances on the absorption and distribution of cadmium in mice
- 1999
-
Ingår i: PHARMACOLOGY & TOXICOLOGY. - : MUNKSGAARD INT PUBL LTD. - 0901-9928. ; 84:6, s. 267-273
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The complex binding of cadmium ions to humic and fulvic acids in water may influence the absorption and distribution of drinking-water Cd in humans. Thus, in the present study mice were given a single oral dose of Cd ((CdCl2)-Cd-109, 25 mu g/l) in 100 mu
|
|
| 37. |
- Nilsson, Bengt-Olof, et al.
(författare)
-
Effects of polyamine synthesis inhibition on polyamines, growth and mechanical properties in hypertrophic rat urinary bladder
- 1998
-
Ingår i: Pharmacology and Toxicology. - 1600-0773. ; 82:6, s. 287-294
-
Tidskriftsartikel (refereegranskat)abstract
- The polyamines putrescine, spermidine and spermine, are ubiquitous intracellular metabolites associated with growth and protein synthesis. In this study effects of polyamine synthesis inhibition on bladder growth, polyamine levels and mechanical properties were investigated in rat urinary bladder subjected to partial outflow obstruction that causes bladder hypertrophy. The S-adenosyl methionine decarboxylase inhibitor CGP-48664 (5 and 20 mg kg-1) was administered alone or in combination with the ornithine decarboxylase inhibitor DFMO (500 mg kg-1), starting one day before creation of partial outflow obstruction and then daily for 7 days. The bladder muscle level of putrescine was increased 38 times and that of spermine reduced by 4 times while spermidine was unchanged after treatment with CGP-48664 (20 mg kg-1). The increase in putrescine was abolished in animals receiving CGP-48664 in combination with DFMO. Treatment with polyamine synthesis inhibitors could not prevent or reduce the hypertrophy of the bladder as judged by bladder wet weight and protein contents. The effects on polyamine quantities were not associated with changes in Ca(2+)-force relationship or in agonist and electrically stimulated force. In summary, treatment of rats with polyamine synthesis inhibitors resulted in changes in polyamine levels in the growing urinary bladder but did not affect growth or mechanical properties.
|
|
| 38. |
- Svedmyr, N, et al.
(författare)
-
The use of beta 2-adrenoceptor agonists in the treatment of bronchial asthma
- 1996
-
Ingår i: Pharmacology and Toxicology. - 1600-0773. ; 78:1, s. 3-11
-
Tidskriftsartikel (refereegranskat)abstract
- All guidelines recommend short-acting inhaled beta 2-adrenoceptor agonists as the first-line drugs in acute asthma attacks and inhaled corticosteroids as the drugs of choice when regular daily treatment is needed. Short-acting inhaled beta 2-adrenoceptor agonists are not effective in reducing nocturnal awakenings because of their short duration of action. In addition there has been an intense debate about the regular use of these drugs. This debate is reviewed. They should only be used on "as needed basis". The Swedish guidelines for the treatment of asthma were the first to recommend the new long-acting inhaled beta 2-adrenoceptor agonists at relatively early stage of the illness (800 micrograms daily of inhaled corticosteroids). Two recently completed large multicentre studies with salmeterol in asthmatics support this opinion. Both studies showed a better asthma control with a combination of a low inhaled steroid dose and salmeterol compared to a doubling of the steroid dose. In most asthmatic patients, still symptomatic on inhaled steroids doses 400 to 800 micrograms daily, a test of the addition of inhaled salmeterol is recommended. The steroid dose can be kept low and safe. However, asthmatic patients with either frequent or severe exacerbations should primarily have their steroid dose increased.
|
|
| 39. |
|
|
| 40. |
- Wallerstedt, S M, et al.
(författare)
-
Characteristics of contractile 5-HT receptors in isolated human omental arteries: presence of 5-HT1 and 5-HT2 receptors
- 1996
-
Ingår i: Pharmacology and Toxicology. - 1600-0773. ; 78:1, s. 50-54
-
Tidskriftsartikel (refereegranskat)abstract
- 5-Hydroxytryptamine (5-HT) has a variety of biological effects, e.g. it induces and modulates vascular smooth muscle activity. The effects are mainly mediated via a hetergenous group of 5-HT receptor subtypes. In order to elucidate the 5-HT receptor mechanisms in the human splanchnic circulation, in vitro studies were carried out on omental arteries obtained from patients undergoing abdominal surgery. Four 5-HT receptor agonists with different selectivity all induced concentration-dependent contraction (potency and order of potency indicated): 5-HT (non-selective; 6.12 +/- 0.14)=sumatriptan (5-HT1; 6.32 +/- 0.07) > alpha-methyl-5-HT (5-HT2; 5.41 +/- 0.05) > 2-methyl-5-HT (5-HT3; < or =4.46+/-0.05). The 5-HT1/5-HT2 receptor antagonist methiothepin antagonised the contraction induced by 5-HT, sumatriptan, alpha-methyl-5-HT and 2-methyl-5-HT. The 5-HT2 receptor antagonist ketanserin antagonised the contraction induced by 5-HT, alpha-methyl-5-HT and 2-methyl-5-HT. The 5-HT3 receptor antagonist tropisetron did not antagonise the contraction elicited by 2-methyl-5-HT. The results suggest that 5-HT-induced conataction in human omental arteries involves both 5-HT1 and 5-HT2, but maybe not 5-HT3-receptors.
|
|
