| 1. |
- Bredhult, Carolina, et al.
(författare)
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Effects of chlorinated biphenyls and metabolites on human uterine myocyte proliferation
- 2007
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Ingår i: Human and Experimental Toxicology. - : SAGE Publications. - 0960-3271 .- 1477-0903. ; 26:10, s. 801-809
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Tidskriftsartikel (refereegranskat)abstract
- Uterine myometrial cells are responsive to sex steroids, which could make them susceptible to actions of endocrine disrupting environmental contaminants such as some PCBs. The aim of this investigation was to identify possible effects of some chlorinated biphenyls (CBs) and their metabolites on myometrial cell proliferation. Myometrial cells obtained from women in both phases of the menstrual cycle and from pregnant women were grown in vitro and exposed to CB 101, CB 118, 3'-MeSO2-CB 101, 4'-MeSO2-CB 101, 4-OH-CB 107, 17 beta-estradiol, progesterone, ethinylestradiol or levonorgestrel. The proliferative activity was studied by a BrdU assay. Myometrial cell cultures originating from pregnant women exhibited decreased proliferation in response to 3'-MeSO2-CB 101, 4'-MeSO2-CB 101 and 4-OH-CB 107. Estradiol, a combination of 1 nM 17 beta-estradiol and 10 nM progesterone, ethinylestradiol and levonorgestrel also reduced the proliferation of the myometrial cells, regardless of whether the cells were collected from either of the menstrual cycle phases or from pregnant women. To our knowledge this study is the first to demonstrate that some CBs affect the proliferative activity of human uterine myocytes.
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| 2. |
- Dandrea, T, et al.
(författare)
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Differential inhibition of inflammatory cytokine release from cultured alveolar macrophages from smokers and non-smokers by NO2
- 1997
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Ingår i: Human & experimental toxicology. - : SAGE Publications. - 0960-3271 .- 1477-0903. ; 16:10, s. 577-588
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Tidskriftsartikel (refereegranskat)abstract
- Human alveolar macrophages (AMs) obtained from smokers and non-smokers by bronchoalveolar lavage (BAL) were subjected to various concentrations of NO2 in an inverted monolayer exposure model. Culture super natants were collected 4 h after the exposure and assayed for secreted TNF-α, IL-1β, IL-8 and MIP-1α. The steady state levels of the mRNAs for these cytokines were also analysed in the cells. The adherence of BAL cells to plastic prior to exposure to the gas elevated the steady state mRNA levels of all four cytokines tested in smoker's cells and that of TNF-α and IL-1β, but not IL-8 (MIP-1α not tested), in non-smoker's cells. Interestingly, adherent cells from non-smokers released circa 15-, 3-,1.5- and 3-fold the amounts of IL-1β, IL-8, TNF-α and MIP-1α, respectively, than smoker's cells during control incubation or exposure to air. A 20 min exposure to NO2 (5 or 20 p.p.m.) did not increase the secretion of any of the cytokines from either cell type. In contrast, NO2 caused a concentration- dependent inhibition of the secretion of all cytokines except IL-1β from smoker's cells. Additionally, NO2 greatly diminished the release of all cytokines in response to further treatment with lipopolysaccharide (LPS). In contrast, only the secretion of TNF-α from non-smoker's cells was inhibited by the gas in a concentration- dependent manner, whilst LPS-induced secretion of the cytokines was not affected by the gas. The steady state levels of the respective mRNAs for each of the cytokines were not significantly affected in smoker's cells by exposure to NO2, except for a negative, dose-dependent trend in the case of TNF-α. Nitrogen dioxide also failed to elevate the levels of the mRNAs in non-smoker's cells but, again, tended to diminish the levels, particularly of IL-1β mRNA. However, exposure to the gas inhibited LPS- induced accumulation of cytokine mRNAs in smoker's cells only. The data suggest that macrophage-derived cytokine mediators of the sepsis response may not play a role in the generation of NO2-induced inflammation in the human lung. Conversely, the gas seems to non-specifically inhibit the release and/or production of cytokines, particularly from smoker's cells, at the post-transcrip tional level, and impairs the ability of the cells to increase the transcription and release of the cytokines in response to bacterial LPS. The fact that NO2 seriously impaired the already diminished capacity of smoker's cells to release several important pro-inflammatory cytokines, both under control conditions and in response to LPS, strongly suggest that the inhalation of NO2 in cigarette smoke may contribute to impairing host defence against infection in the lung.
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| 3. |
- Edling, Christer, et al.
(författare)
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Positron emission tomography studies of healthy volunteers : No effects on the dopaminergic terminals and synthesis after short-term exposure to toluene
- 1997
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Ingår i: Human and Experimental Toxicology. - : SAGE Publications. - 0960-3271 .- 1477-0903. ; 16:3, s. 171-176
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Tidskriftsartikel (refereegranskat)abstract
- Despite extensive research, the mechanisms for the effects of organic solvents on the central nervous system are still unknown. One mechanism proposed is that solvents interfere with the synthesis of neurotransmitters. In the present study 11 male healthy volunteers were exposed during 15 min to 100 p.p.m. toluene at light physical exercise, and the dopamine decarboxylase activity and number of terminals in putamen were measured before and after exposure by positron emission tomography. Two different tracers were used [beta-11C]L-DOPA for decarboxylase activity during the in vivo synthesis of dopamine, and [11C]nomifensine to estimate the number of terminals. Although there was a slight increase in the rate of dopamine synthesis in the putamen after the exposure, this difference was not statistically significant (P = 0.4). No effect was observed with regard to the uptake of nomifensine. There was no significant relationship between the dose of toluene and rate of dopamine synthesis, and no significant correlation between the time from end of exposure to start of the PET-camera and DOPA. Our findings indicate that short term exposure to 100 p.p.m. of toluene does not affect the rate of dopamine synthesis or the number of presynaptic terminals.
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| 4. |
- Ernstgard, L, et al.
(författare)
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Acute effects of exposure to vapours of dioxane in humans
- 2006
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Ingår i: Human & experimental toxicology. - : SAGE Publications. - 0960-3271 .- 1477-0903. ; 25:12, s. 723-729
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Tidskriftsartikel (refereegranskat)abstract
- Information on the acute effects associated with the handling of 1,4-dioxane is sparse. Our aim was to evaluate the acute effects of 1,4-dioxane vapours. In a screening study, six healthy volunteers rated symptoms on a visual analogue scale (VAS), while exposed to stepwise increasing levels of 1,4-dioxane, from 1 to 20 ppm. The initial study indicated no increased ratings at any of the exposure levels; we decided to use 20 ppm (72 mg/m3) as a tentative no observed adverse effect level (NOAEL). In the main study, six female and six male healthy volunteers were exposed to 0 (control exposure) and 20 ppm 1,4-dioxane vapour, for 2 hours at rest. The volunteers rated 10 symptoms on VAS before, during, and after the exposure. Blink frequency was monitored during exposure. Pulmonary function, and nasal swelling, was measured before, and at 0 and 3 hours after exposure. Inflammatory markers in plasma (C-reactive protein, and interleukin-6) were measured before and at 3 hours after exposure. In conclusion, exposure to 20 ppm 1,4-dioxane for 2 hours did not significantly affect symptom ratings, blink frequency, pulmonary function, nasal swelling, or inflammatory markers in the plasma of the 12 volunteers in our study.
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| 5. |
- Forsberg, M, et al.
(författare)
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No support for lipid rescue in oral poisoning: A systematic review and analysis of 160 published cases
- 2017
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Ingår i: Human & experimental toxicology. - : SAGE Publications. - 1477-0903 .- 0960-3271. ; 36:5, s. 461-466
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Tidskriftsartikel (refereegranskat)abstract
- Lipid rescue is used as treatment of various poisonings despite weak scientific evidence. Some experimental studies have indicated a positive effect, but others have not. Clinical studies are lacking, wherefore a systematic review of virtually all published human case reports is presented. The case reports were searched for in PubMed and Web of Science and examined by two experts according to an assessment form grading the probability for a causal connection between lipid rescue and improved symptoms. A total of 160 cases were finally included, of which 30 had no positive effect of lipid rescue. Among the 130 included cases with alleged positive effect, 94 were oral poisonings and 36 were cases with local anesthetic systemic toxicity (LAST). The experts’ assessment resulted in a “certain” causal connection in three cases with LAST but not in oral poisoning. Moreover, the mean assessment score among the oral poisonings was significantly worse than the corresponding score in the cases with LAST. The average log p-value of the main toxins among the oral poisonings was significantly lower than the corresponding p-value in the cases with LAST. Among the oral poisonings, 91% had received some other resuscitative treatment more or less simultaneously with lipid rescue. Considering the findings of this study and the increasingly reported adverse effects of lipid rescue, it’s reasonable to strictly limit its use in clinical practice. We would not recommend it in oral poisonings.
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| 6. |
- Forsby, Anna, et al.
(författare)
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Integration of in vitro neurotoxicity data with biokinetic modelling for the estimation of in vivo neurotoxicity.
- 2007
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Ingår i: Human and Experimental Toxicology. - : SAGE Publications. - 0960-3271 .- 1477-0903. ; 26:4, s. 333-338
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Tidskriftsartikel (refereegranskat)abstract
- Risk assessment of neurotoxicity is mainly based on in vivo exposure, followed by tests on behaviour, physiology and pathology. In this study, an attempt to estimate lowest observed neurotoxic doses after single or repeated dose exposure was performed. Differentiated human neuroblastoma SH-SY5Y cells were exposed to acrylamide, lindane, parathion, paraoxon, phenytoin, diazepam or caffeine for 72 hours. The effects on protein synthesis and intracellular free Ca2+ concentration were studied as physiological endpoints. Voltage operated Ca2+ channel function, acetylcholine receptor function and neurite degenerative effects were investigated as neurospecific endpoints for excitability, cholinergic signal transduction and axonopathy, respectively. The general cytotoxicity, determined as the total cellular protein levels after the 72 hours exposure period, was used for comparison to the specific endpoints and for estimation of acute lethality. The lowest concentration that induced 20% effect (EC20) obtained for each compound, was used as a surrogate for the lowest neurotoxic level (LOEL) at the target site in vivo. The LOELs were integrated with data on adsorption, distribution, metabolism and excretion of the compounds in physiologically-based biokinetic (PBBK) models of the rat and the lowest observed effective doses (LOEDs) were estimated for the test compounds. A good correlation was observed between the estimated LOEDs and experimental LOEDs found in literature for rat for all test compounds, except for diazepam. However, when using in vitro data from the literature on diazepam's effect on gamma-amino butyric acid (GABA)A receptor function for the estimation of LOED, the correlation between the estimated and experimental LOEDs was improved from a 10,000-fold to a 10-fold difference. Our results indicate that it is possible to estimate LOEDs by integrating in vitro toxicity data as surrogates for lowest observed target tissue levels with PBBK models, provided that some knowledge about toxic mechanisms is known.
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| 7. |
- Hansson, Sven Ove
(författare)
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Ethical principles for hormesis policies
- 2008
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Ingår i: Human and Experimental Toxicology. - : SAGE Publications. - 0960-3271 .- 1477-0903. ; 28, s. 609-612
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Tidskriftsartikel (refereegranskat)abstract
- At least two major choices have to be made in the ethical analysis of hormesis policies. The first is where to put the burden of proof when it is uncertain whether a particular hormesis effect exists or not. It is argued that the burden of proof will have to fall primarily on those who claim the existence of such an effect. The second issue arises when (positive) hormesis effects of a substance are weighed against negative effects of the same substance. A decision must then be made whether negative effects affecting one person can be outweighed by positive effects on another person or only by positive effects on that person herself. It is argued that risk-weighing for hormesis effects should be individualistic. This would mean that benefits for one person do not automatically outweigh negative effects on another person.
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| 8. |
- Hojer, J
(författare)
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Severe metabolic acidosis in the alcoholic: differential diagnosis and management
- 1996
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Ingår i: Human & experimental toxicology. - : SAGE Publications. - 0960-3271 .- 1477-0903. ; 15:6, s. 482-488
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Tidskriftsartikel (refereegranskat)abstract
- 1 A chronic alcoholic with severe metabolic acidosis presents a difficult diagnostic problem. The most common cause is alcoholic ketoacidosis, a syndrome with a typical history but often misleading laboratory findings. This paper will focus on this important and probably underdiagnosed syndrome. 2 The disorder occurs in alcoholics who have had a heavy drinking-bout culminating in severe vomiting, with resulting dehydration, starvation, and then a β- hydroxybutyrate dominated ketoacidosis. 3 Awareness of this syndrome, thorough history-taking, physical examination and routine laboratory analyses will usually lead to a correct diagnosis. 4 The treatment is simply replacement of fluid, glucose, electrolytes and thiamine. Insulin or alkali should be avoided. 5 The most important differential diagnoses are diabetic ketoacidosis, lactic acidosis and salicylate, methanol or ethylene glycol poisoning, conditions which require quite different treatment. 6 The diagnostic management of unclear cases should always include toxicological tests, urine microscopy for calcium oxalate crystals and calculation of the serum anion and osmolal gaps. 7 It is suggested here, however, that the value of the osmolal gap should be considered against a higher reference limit than has previously been recom mended. An osmolal gap above 25 mosm/kg, in a patient with an increased anion gap acidosis, is a strong indicator of methanol or ethylene glycol intoxication.
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| 9. |
- Jones, AW, et al.
(författare)
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Alcohol concentrations in post-mortem body fluids
- 2006
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Ingår i: Human & experimental toxicology. - : SAGE Publications. - 0960-3271 .- 1477-0903. ; 25:11, s. 623-624
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Jones, A Wayne, 1945-, et al.
(författare)
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Relation between blood- and urine-amphetamine concentrations in impaired drivers as influenced by urinary pH and creatinine
- 2005
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Ingår i: Human and Experimental Toxicology. - : SAGE Publications. - 0960-3271 .- 1477-0903. ; 24:12, s. 615-622
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Tidskriftsartikel (refereegranskat)abstract
- Amphetamine undergoes extensive renal excretion and significant amounts are present in urine as the unchanged parent drug. This prompted us to investigate whether a quantitative relationship existed between blood and urine concentrations of amphetamine in the body fluids of drug-impaired drivers apprehended in Sweden, where this stimulant is the major drug of abuse. The relationship between blood and urine concentrations of amphetamine was determined by multivariate analysis with urinary pH and creatinine as predictor variables. Amphetamine was determined in blood and urine by gas chromatography-mass spectrometry with deuterium-labelled internal standards. The concentration of amphetamine in urine was about 200 times greater than the concentration in blood, the mean and median urine/blood ratios were 214 and 160, respectively, with large individual variations. The Pearson correlation coefficient between urine (y) and blood (x) amphetamine was r= 0.53, n=48, which was statistically highly significant (P < 0.001), although the residual standard deviation (SD) was large (±181 mg/L). The correlation coefficient increased (r=0.60) when the concentration of amphetamine in urine was normalized for dilution by dividing with the creatinine content. When urinary pH and creatinine were both included as predictor variables, the correlation coefficient was even higher (r=0.69), now explaining 48% (r 2=0.48) of the variation in urine-amphetamine concentration. However, the partial regression coefficient for creatinine (53±28.7) was not statistically significant (t=1.85, P >0.05), whereas the corresponding regression coefficient for pH was highly significant and had a negative sign (-102±32.6, t= -3.12, P
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