Neuroendocrinologists are now realising that the brain-pituitary relationships in man are more co... more Neuroendocrinologists are now realising that the brain-pituitary relationships in man are more complex than they had previously thought. It seems that the brain is also a gland, whereas the pituitary produces neuropeptide hormones which work in the brain. Since most substances which carry information between those two neuroendocrine partners are present in cerebrospinal fluid, it is natural to assume that cerebrospinal fluid has an important role as a carrier of molecular signals between the brain and pituitary. Whether or not the analysis of cerebrospinal fluid neuropeptide hormones will give more information about the brain activity in neurological and psychiatric patients is not yet known exactly despite some promising new findings.
In order to elucidate the interplay of prolactin and dopamine in schizophrenia, base-line levels ... more In order to elucidate the interplay of prolactin and dopamine in schizophrenia, base-line levels of prolactin were assayed in the cerebrospinal fluid (CSF) of chronic schizophrenic patients with or without lobotomy. Cental and cortical atrophy and significantly lowered CSF prolactin levels were found in lobotomized patients in comparison to equally neuroleptic-treated non-lobotomized patients. The mean CSF prolactin level in the female patients was significantly higher than in the male patients. This study did not support the 'dopamine hypothesis' of schizophrenia, since CSF prolactin levels did not correlate with schizophrenic symptoms. The brain atrophy blocked completely the expected elevation of CSF prolactin levels induced by neuroleptics.
Chip pile workers are exposed to high concentrations of airborne mould spores. Few sporadic cases... more Chip pile workers are exposed to high concentrations of airborne mould spores. Few sporadic cases of allergic alveolitis have been reported in Finland. Eight non‐smoking workers, six on chip piles and two on bark piles, were examined to study the immunological and clinical response to continuous mould spore exposure. The spore exposure ranged between 104 and 105 spores/m3. Three of the six chip pile workers had precipitating serum antibodies against Aspergillus fumigatus. The three antibody‐positive workers had a tendency to decreased total pulmonary diffusion capacity and vital capacity. Significant respiratory symptoms were not noted. Long‐term spore exposure may include an occupational health risk to chip pile workers.
ABSTRACT 1. Rats were exposed to m-xylene (300 ppm) and methyl ethyl ketone (MEK, 600 ppm) vapour... more ABSTRACT 1. Rats were exposed to m-xylene (300 ppm) and methyl ethyl ketone (MEK, 600 ppm) vapour, separately and in combination. 2. Repeated exposures to m-xylene enhanced liver drug-metabolizing capacity, whereas MEK showed no effects. After mixed exposure the cytochrome P-450-dependent monooxygenase activities were additively or synergistically induced. 3. In the presence of MEK the overall metabolism of xylene was strongly inhibited both after single and repeated exposures, an effect accompanied by elevation of xylene concentration in blood (18-29%) and fat (25-32%). 4. The 24-h excretion of the urine metabolites of m-xylene was decreased by 22-24% in mixed exposures: the excretion of methylhippuric acid was decreased (29%), but that of 2,4-dimethylphenol increased (9-35%). 5. After repeated inhalation exposures the excretion of xylene metabolites in urine was consistently higher, whereas the concentrations of xylene in fat (but not the concentration of MEK) were lower than after a single treatment, conceivably due to accelerated metabolic clearance of xylene. 6. Thioether excretion in urine was enhanced in xylene-treated rats (7-13-fold), but was not influenced by the induced changes in the metabolism of xylene. Xylene inhalation caused liver GSH to decrease slightly (10%), as did inhalation of MEK, but the latter did not enhance the excretion of thioethers. 7. MEK is a potent inhibitor of the side-chain oxidation of m-xylene producing methylhippuric acid, but not of its ring oxidation to 2,4-dimethylphenol, and exhibits a synergistic inducing effect on liver enzymes responsible for the oxidation of m-xylene. The increased ring oxidation of m-xylene was not associated with increased production of reactive metabolites indicated by GSH-depletion or thioether formation.
International Archives of Occupational and Environmental Health, 1988
The kinetics of inhaled methyl ethyl ketone (MEK) in human volunteers was studied in an exposure ... more The kinetics of inhaled methyl ethyl ketone (MEK) in human volunteers was studied in an exposure chamber. Relative pulmonary uptake was about 53% throughout a 4-h exposure period at 200 ppm. Blood MEK concentration rose steadily until the end of exposure. Repeated bicycle exercise increased the overall blood MEK level markedly in comparison to sedentary activity, with transient peaks in association with cycling; thus blood MEK concentration depended both on the rate of uptake and the amount taken up. Only 3% of the absorbed dose was excreted unchanged by exhalation. A well-known metabolite of MEK, 2,3-butanediol, was detected in the urine with maximum rates of excretion at about 6 to 12 h from the beginning of exposure. About 2% of the MEK dose taken up by the lungs was excreted in the urine as 2,3-butanediol. The main part of inhaled MEK is supposedly metabolized in the intermediary metabolism. Elimination of MEK in blood appeared to exhibit two phases: the initial alpha-phase (T1/2 = 30 min; kel alpha = 0.023) over the first post-exposure hour, followed by the terminal beta-phase (T1/2 = 81 min; kel beta = 0.009).
Prolactin (PRL) among other pituitary hormones has been detected in human cerebrospinal fluid (CS... more Prolactin (PRL) among other pituitary hormones has been detected in human cerebrospinal fluid (CSF) (2.,7.,8.). The normal CSF prolactin concentration is about 1 ng/ml (2.,3.). Patients with prolactin secreting hvpophyseal tumor have elevated PRL levels both in their blood and cerebrospinal fluid. The suprasellar extension of prolactinoma can brinq about higher prolactin concentration in the CSF than that in the serum ( 5 . , 9 . ) . Under physiological conditions serum and CSF prolactin concentrations are linearly correlated ( 2 . ) . This correlation prevails also at slightly elevated serum prolactin levels. In order to further investigate the interrelationship of the serum and CSF prolactin strictly normoprolactinemic neurological patients were chosen to this study.
ABSTRACT 1. Rats were exposed to m-xylene (300 ppm) and methyl ethyl ketone (MEK, 600 ppm) vapour... more ABSTRACT 1. Rats were exposed to m-xylene (300 ppm) and methyl ethyl ketone (MEK, 600 ppm) vapour, separately and in combination. 2. Repeated exposures to m-xylene enhanced liver drug-metabolizing capacity, whereas MEK showed no effects. After mixed exposure the cytochrome P-450-dependent monooxygenase activities were additively or synergistically induced. 3. In the presence of MEK the overall metabolism of xylene was strongly inhibited both after single and repeated exposures, an effect accompanied by elevation of xylene concentration in blood (18-29%) and fat (25-32%). 4. The 24-h excretion of the urine metabolites of m-xylene was decreased by 22-24% in mixed exposures: the excretion of methylhippuric acid was decreased (29%), but that of 2,4-dimethylphenol increased (9-35%). 5. After repeated inhalation exposures the excretion of xylene metabolites in urine was consistently higher, whereas the concentrations of xylene in fat (but not the concentration of MEK) were lower than after a single treatment, conceivably due to accelerated metabolic clearance of xylene. 6. Thioether excretion in urine was enhanced in xylene-treated rats (7-13-fold), but was not influenced by the induced changes in the metabolism of xylene. Xylene inhalation caused liver GSH to decrease slightly (10%), as did inhalation of MEK, but the latter did not enhance the excretion of thioethers. 7. MEK is a potent inhibitor of the side-chain oxidation of m-xylene producing methylhippuric acid, but not of its ring oxidation to 2,4-dimethylphenol, and exhibits a synergistic inducing effect on liver enzymes responsible for the oxidation of m-xylene. The increased ring oxidation of m-xylene was not associated with increased production of reactive metabolites indicated by GSH-depletion or thioether formation.
Finnish doctors are pioneers in the production and utilization of evidence-based recommendations ... more Finnish doctors are pioneers in the production and utilization of evidence-based recommendations in healthcare. Doctor's databases were established by the end of the 1980s and Current Care guidelines have been devised since 1994. In evidence-based recommendations it is essential to provide the user with a description of the quality of research data used as the basis for the recommendation. Consistent, applicable and transparent methods are helpful in the judgment of the quality of studies and strength of evidence. In this article we describe the judgment of the level of evidence and the strength of recommendations according to the international GRADE working group.
Neuroendocrinologists are now realising that the brain-pituitary relationships in man are more co... more Neuroendocrinologists are now realising that the brain-pituitary relationships in man are more complex than they had previously thought. It seems that the brain is also a gland, whereas the pituitary produces neuropeptide hormones which work in the brain. Since most substances which carry information between those two neuroendocrine partners are present in cerebrospinal fluid, it is natural to assume that cerebrospinal fluid has an important role as a carrier of molecular signals between the brain and pituitary. Whether or not the analysis of cerebrospinal fluid neuropeptide hormones will give more information about the brain activity in neurological and psychiatric patients is not yet known exactly despite some promising new findings.
In order to elucidate the interplay of prolactin and dopamine in schizophrenia, base-line levels ... more In order to elucidate the interplay of prolactin and dopamine in schizophrenia, base-line levels of prolactin were assayed in the cerebrospinal fluid (CSF) of chronic schizophrenic patients with or without lobotomy. Cental and cortical atrophy and significantly lowered CSF prolactin levels were found in lobotomized patients in comparison to equally neuroleptic-treated non-lobotomized patients. The mean CSF prolactin level in the female patients was significantly higher than in the male patients. This study did not support the 'dopamine hypothesis' of schizophrenia, since CSF prolactin levels did not correlate with schizophrenic symptoms. The brain atrophy blocked completely the expected elevation of CSF prolactin levels induced by neuroleptics.
Chip pile workers are exposed to high concentrations of airborne mould spores. Few sporadic cases... more Chip pile workers are exposed to high concentrations of airborne mould spores. Few sporadic cases of allergic alveolitis have been reported in Finland. Eight non‐smoking workers, six on chip piles and two on bark piles, were examined to study the immunological and clinical response to continuous mould spore exposure. The spore exposure ranged between 104 and 105 spores/m3. Three of the six chip pile workers had precipitating serum antibodies against Aspergillus fumigatus. The three antibody‐positive workers had a tendency to decreased total pulmonary diffusion capacity and vital capacity. Significant respiratory symptoms were not noted. Long‐term spore exposure may include an occupational health risk to chip pile workers.
ABSTRACT 1. Rats were exposed to m-xylene (300 ppm) and methyl ethyl ketone (MEK, 600 ppm) vapour... more ABSTRACT 1. Rats were exposed to m-xylene (300 ppm) and methyl ethyl ketone (MEK, 600 ppm) vapour, separately and in combination. 2. Repeated exposures to m-xylene enhanced liver drug-metabolizing capacity, whereas MEK showed no effects. After mixed exposure the cytochrome P-450-dependent monooxygenase activities were additively or synergistically induced. 3. In the presence of MEK the overall metabolism of xylene was strongly inhibited both after single and repeated exposures, an effect accompanied by elevation of xylene concentration in blood (18-29%) and fat (25-32%). 4. The 24-h excretion of the urine metabolites of m-xylene was decreased by 22-24% in mixed exposures: the excretion of methylhippuric acid was decreased (29%), but that of 2,4-dimethylphenol increased (9-35%). 5. After repeated inhalation exposures the excretion of xylene metabolites in urine was consistently higher, whereas the concentrations of xylene in fat (but not the concentration of MEK) were lower than after a single treatment, conceivably due to accelerated metabolic clearance of xylene. 6. Thioether excretion in urine was enhanced in xylene-treated rats (7-13-fold), but was not influenced by the induced changes in the metabolism of xylene. Xylene inhalation caused liver GSH to decrease slightly (10%), as did inhalation of MEK, but the latter did not enhance the excretion of thioethers. 7. MEK is a potent inhibitor of the side-chain oxidation of m-xylene producing methylhippuric acid, but not of its ring oxidation to 2,4-dimethylphenol, and exhibits a synergistic inducing effect on liver enzymes responsible for the oxidation of m-xylene. The increased ring oxidation of m-xylene was not associated with increased production of reactive metabolites indicated by GSH-depletion or thioether formation.
International Archives of Occupational and Environmental Health, 1988
The kinetics of inhaled methyl ethyl ketone (MEK) in human volunteers was studied in an exposure ... more The kinetics of inhaled methyl ethyl ketone (MEK) in human volunteers was studied in an exposure chamber. Relative pulmonary uptake was about 53% throughout a 4-h exposure period at 200 ppm. Blood MEK concentration rose steadily until the end of exposure. Repeated bicycle exercise increased the overall blood MEK level markedly in comparison to sedentary activity, with transient peaks in association with cycling; thus blood MEK concentration depended both on the rate of uptake and the amount taken up. Only 3% of the absorbed dose was excreted unchanged by exhalation. A well-known metabolite of MEK, 2,3-butanediol, was detected in the urine with maximum rates of excretion at about 6 to 12 h from the beginning of exposure. About 2% of the MEK dose taken up by the lungs was excreted in the urine as 2,3-butanediol. The main part of inhaled MEK is supposedly metabolized in the intermediary metabolism. Elimination of MEK in blood appeared to exhibit two phases: the initial alpha-phase (T1/2 = 30 min; kel alpha = 0.023) over the first post-exposure hour, followed by the terminal beta-phase (T1/2 = 81 min; kel beta = 0.009).
Prolactin (PRL) among other pituitary hormones has been detected in human cerebrospinal fluid (CS... more Prolactin (PRL) among other pituitary hormones has been detected in human cerebrospinal fluid (CSF) (2.,7.,8.). The normal CSF prolactin concentration is about 1 ng/ml (2.,3.). Patients with prolactin secreting hvpophyseal tumor have elevated PRL levels both in their blood and cerebrospinal fluid. The suprasellar extension of prolactinoma can brinq about higher prolactin concentration in the CSF than that in the serum ( 5 . , 9 . ) . Under physiological conditions serum and CSF prolactin concentrations are linearly correlated ( 2 . ) . This correlation prevails also at slightly elevated serum prolactin levels. In order to further investigate the interrelationship of the serum and CSF prolactin strictly normoprolactinemic neurological patients were chosen to this study.
ABSTRACT 1. Rats were exposed to m-xylene (300 ppm) and methyl ethyl ketone (MEK, 600 ppm) vapour... more ABSTRACT 1. Rats were exposed to m-xylene (300 ppm) and methyl ethyl ketone (MEK, 600 ppm) vapour, separately and in combination. 2. Repeated exposures to m-xylene enhanced liver drug-metabolizing capacity, whereas MEK showed no effects. After mixed exposure the cytochrome P-450-dependent monooxygenase activities were additively or synergistically induced. 3. In the presence of MEK the overall metabolism of xylene was strongly inhibited both after single and repeated exposures, an effect accompanied by elevation of xylene concentration in blood (18-29%) and fat (25-32%). 4. The 24-h excretion of the urine metabolites of m-xylene was decreased by 22-24% in mixed exposures: the excretion of methylhippuric acid was decreased (29%), but that of 2,4-dimethylphenol increased (9-35%). 5. After repeated inhalation exposures the excretion of xylene metabolites in urine was consistently higher, whereas the concentrations of xylene in fat (but not the concentration of MEK) were lower than after a single treatment, conceivably due to accelerated metabolic clearance of xylene. 6. Thioether excretion in urine was enhanced in xylene-treated rats (7-13-fold), but was not influenced by the induced changes in the metabolism of xylene. Xylene inhalation caused liver GSH to decrease slightly (10%), as did inhalation of MEK, but the latter did not enhance the excretion of thioethers. 7. MEK is a potent inhibitor of the side-chain oxidation of m-xylene producing methylhippuric acid, but not of its ring oxidation to 2,4-dimethylphenol, and exhibits a synergistic inducing effect on liver enzymes responsible for the oxidation of m-xylene. The increased ring oxidation of m-xylene was not associated with increased production of reactive metabolites indicated by GSH-depletion or thioether formation.
Finnish doctors are pioneers in the production and utilization of evidence-based recommendations ... more Finnish doctors are pioneers in the production and utilization of evidence-based recommendations in healthcare. Doctor's databases were established by the end of the 1980s and Current Care guidelines have been devised since 1994. In evidence-based recommendations it is essential to provide the user with a description of the quality of research data used as the basis for the recommendation. Consistent, applicable and transparent methods are helpful in the judgment of the quality of studies and strength of evidence. In this article we describe the judgment of the level of evidence and the strength of recommendations according to the international GRADE working group.
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