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T Hansson

Publications and source records attributed to T Hansson.

At least 109 records · Page 6Linked to original sources

Immunohistochemical localization of cytochrome P-450 in the rat brain.

Immunohistochemical localization of cytochrome P-450 in the brains of normal untreated male rats has been demonstrated with polyclonal antibodies raised against hepatic P-450C. These antibodies recognize P-450C and D, two closely related forms of P-450. We have identified P-450C,D immunoreactivity (P-450C,D-i) within both neurons and glial cells. Neuronal cell bodies showing P-450C,D-i were present in several forebrain areas, including the olfactory bulb, the caudate nucleus, the cingulate, the frontal and the entorhinal cortex, the hippocampus and the thalamus. In the brainstem, P-450C,D-i neurons were detected in the substantia nigra, the nucleus locus coeruleus, raphe nucleus, reticular formation and the trigeminal nerve nucleus and the dorsal motor nucleus of the vagus. Glial cells containing P-450C,D-i were situated within myelinated fiber tracts in the forebrain (e.g. the corpus callosum, the internal capsule) and the brainstem (e.g. the superior cerebellar peduncle, the medial longitudinal fasciculus). Some, but not all, of the P-450C,D-i glial cells also stained with an antibody against glial fibrillary acidic protein. The present findings represent the first immunohistochemical demonstration of cytochrome P-450 in the brain and suggest that cytochrome P-450C,D is constitutive in neurons and glial cells of most brain regions throughout the rat neuraxis.

Animals↗

Effects of toluene treatment in vivo and in vitro on the binding characteristics of [3H]neurotensin in rat striatal membranes.

The effects of treatment with toluene in vivo (80 ppm, 3 days, 6 h/day) and in vitro (19 mumol/ml) were analyzed on the binding characteristics of [3H]neurotensin in rat striatal membranes. Exposure to toluene in vivo did not produce any significant effects on the binding characteristics of [3H]neurotensin. However, the addition of toluene in vitro caused a trend for a decreased Bmax value and produced a significantly reduced KD value of [3H]neurotensin binding. The absence of effects at 80 ppm indicates that the neurotensin receptor is relatively insensitive to toluene exposure, in contrast to, e.g. the dopamine agonist binding sites. Furthermore, the toluene response of the neurotensin receptor, as seen after treatment in vitro, is different from the responses seen in many monoamine receptors, which show decreased affinities following toluene exposure. It is possible that toluene is mediating its effects on the neurotensin receptor by changing the lipid micro-environment in which the receptor is situated. Another explanation would be that toluene selectively acts on the monoamine receptors, e.g. the more sensitive dopamine receptors, which through receptor-receptor interactions would cause the response seen in the neurotensin receptor. However, it cannot be excluded that the suggested receptor-receptor interaction itself is affected by toluene.

Administration, Inhalation↗

Toluene induces changes in the morphology of astroglia and neurons in striatal primary cell cultures.

Toluene (4.7-150) mumol per ml) was added for 30 or 60 min to astroglial and neuronal primary cell cultures from rat striatum and changes in cell morphology were analyzed by light microscopy. After 60 min incubation in 40 mumol toluene/ml, the cell bodies of the astrocytes appeared contracted, and their processes and nuclei were clearly visible. At higher doses of toluene the astrocytes seemed to be flattened and major cell damage was visualized by the uptake of vital dyes. The neurons, however, became affected and judged by morphological criteria only at the higher toluene doses. In conclusion, toluene induced morphological changes in primary astrocyte cultures and also in primary neuronal cultures at higher toluene concentrations.

Animals↗

Pressure changes following constriction of the cauda equina. An experimental study in situ.

During routine autopsies in 11 cadavers, the intact dural sac, including its nerve roots, was circumferentially constricted by a clamp while the pressure under the clamp among the nerve roots was recorded simultaneously. The first sign of a pressure increase--the critical size--occurred at a cross-sectional area of the cauda equina of 77 +/- 13 mm2. To achieve a pressure increase of 50 mm Hg, the cross-sectional area of the cauda equina had to be further constricted at an average of 19 +/- 8%. The corresponding constriction needed to achieve a pressure of 100 mm Hg was 26 +/- 8%. The results indicated that constriction of the cauda equina to a size less than 75 mm2 probably will affect the normal function of the nerve roots of the cauda.

Aged↗

Regional distribution of cytochrome P-450 in the rat brain: spectral quantitation and contribution of P-450b,e, and P-450c,d.

The cytochrome P-450 (P-450) content of different regions of the rat brain was measured after partial purification of the enzyme from homogenates, and the quantitative contribution of P-450b,e and P-450c,d to brain P-450 was assessed by Western immunoblotting and immunohistochemistry using rabbit antibodies raised against purified hepatic P-450b and P-450c, respectively). P-450 could be quantitated by its reduced CO difference spectrum after chromatography of homogenates on p-chloroamphetamine-coupled Sepharose. The yield of P-450 from whole brain was 90 +/- 19 pmol/g of tissue, which is approximately 1% of the level in liver microsomes from control rats. The amount of P-450 recovered from homogenates of olfactory lobes, hypothalamus, thalamus, striatum, cerebral cortex, and brainstem varied between 40 and 100 pmol/g of tissue. The cerebellum was a region of exceptionally high P-450 content, with yields of up to 400 pmol/g whereas the substantia nigra yielded only 16-20 pmol/g. Immunohistochemical studies with anti-P-450b and anti-P-450c revealed intense staining of a limited number of cells in the cerebellum with both antibodies and in the thalamus only with anti-P-450c. In the cerebellum, both anti-P-450b and anti-P-450c stained the Bergmann glial cells together with their radial processes. Individual glial cells in the granular cell layer were also stained. There was no staining of Purkinje cells. In the thalamus, anti-P-450b gave weak staining of certain astroglia, but with anti-P-450c, there was intense staining of neuronal somata.(ABSTRACT TRUNCATED AT 250 WORDS)

7-Alkoxycoumarin O-Dealkylase↗

Effects of acute haloperidol treatment on regional catecholamine levels and utilization in rats exposed to toluene.

The aim of the present investigation was to evaluate whether the responses of central catecholamine (CA) neurons to CA receptor blockade by haloperidol are altered upon toluene exposure. Male rats were exposed to air or toluene (80 ppm) for 5 and 4 days, 6 h day-1. CA levels and utilization were determined in discrete regions of the forebrain and hypothalamus as well as in the substantia nigra (SN) and anteromedial frontal cortex (AMFC). Serum levels of corticosterone, thyroid stimulating hormone, luteinizing hormone and prolactin were determined by radioimmunoassay procedures. Toluene exposure led to increased dopamine (DA) utilization in the AMFC and increased CA utilization in the paraventricular hypothalamic nuclei. In air-exposed rats haloperidol (1 mg kg-1, i.p., 2 h before killing) increased DA utilization in the marginal part of the nucleus caudatus putamen (CAUD). In toluene-exposed rats, haloperidol induced significant depletions of DA stores in the SN and in the medial and central parts of the CAUD. In the posterior nucleus accumbens (ACC) DA utilization was significantly increased. Combined haloperidol and toluene treatment selectively decreased DA levels in the ACC and SN, and significantly increased DA utilization in the CAUD, as compared with the air-exposed control group. Furthermore, after combined treatment, there was a specific increase in noradrenaline (NA) utilization in the SN and in CA utilization in the medial palisade zone of the median eminence. Serum prolactin levels were substantially raised in both the air and toluene groups after the haloperidol treatment. In conclusion, acute haloperidol treatment preferentially reduces DA levels and increases DA and NA utilization in the SN and in discrete tel- and diencephalic areas in rats exposed to toluene.

Animals↗

Bone mineral content in normally menstruating women with hyperprolactinaemia.

Decreased bone density has been reported in women with hyperprolactinaemia due to pituitary tumours. We identified a number of seemingly healthy women with hyperprolactinaemia, i.e. a serum prolactin concentration exceeding 500 mU/l (25 micrograms/l) on three occasions, during a study in 1980/1981 of a representative population sample of greater than 1,400 women in seven different age strata (range 26-72 years). We compared vertebral bone mineral content and bone mineral areal content in 5 hyperprolactinaemic normally menstruating 50-year-old women with that of 6 controls matched for age and menstrual status but found no difference. Since the degree of prolactin elevation was similar in our study group to that previously reported for hyperprolactinaemic subjects with pituitary tumours and the time of exposure to raised hormone concentration appears to be of the same magnitude, other hormonal changes than hyperprolactinaemia per se seem to be the cause of low bone mineral content in women with hyperprolactinaemia and amenorrhoea.

Alkaline Phosphatase↗

Oestradiol synergizes with 5 alpha-dihydrotestosterone or 3 alpha- but not 3 beta-androstanediol in inducing sexual behaviour in castrated rats.

Castrated male rats were treated with constant-release implants filled with testosterone, oestradiol-17 beta, 17 beta-hydroxy-5 alpha-androstan-3-one (5 alpha-dihydrotestosterone; DHT), 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-Adiol) or 5 alpha-androstane-3 beta,17 beta-diol (3 beta-Adiol). Only testosterone activated the sexual behaviour of the rats. If combined with oestradiol, DHT or 3 alpha-Adiol induced the behaviour, but 3 beta-Adiol failed to have this effect. Oestradiol inhibited the in-vitro formation of [14C]Adiols from [14C]DHT by combined preoptic and hypothalamic tissue, but only when given in high doses. No effect on the formation of [14C]Adiols from [14C]DHT was found in rats treated in vivo with DHT or with the combination of DHT and oestradiol which effectively stimulated sexual behaviour. These results do not support the suggestion that oestradiol may synergize with androgens to induce sexual behaviour in castrated rats by inhibiting androgen metabolism.

Androstane-3,17-diol↗

Fatigue fracture morphology in human lumbar motion segments.

The fatigue behavior of 17 fresh lumbar spine motion segments was examined during cyclic, axial, compressive loading. The loading frequency and magnitude were chosen to simulate vigorous physiological loading conditions. The average failure occurred after 318 such loading cycles. Two main types of failure occurred and both involved the endplate and the adjacent subchondral spongy bone of the vertebral body. A tendency was observed toward a relation between the degree of disk degeneration and fracture type. Location of the fatigue fractures corresponded to the location of earlier detected microcalluses of the spongy trabeculae in the vertebral body. The findings further demonstrated that, under repetitive physiological loading, the weakest part of the lumbar motion segment was the endplate and the adjacent spongy bone.

Adult↗

Cytochrome P-450 b and c in the rat brain and pituitary gland.

A quantitative assessment of the levels of cytochromes P-450 b and P-450 c in the brains and pituitary glands of untreated and beta-naphthoflavone (BNF)-pretreated rats was made with polyclonal antibodies raised against hepatic P-450 b and c and the sensitive fluorometric assay of P-450 catalytic activity, namely, the O-deethylation of ethoxycoumarin (ETC). In the microsomal fraction of brains of untreated rats, the rate of formation of 7-hydroxycoumarin from ETC ranged between 0.1 and 20 pmol/min/mg of microsomal protein, which is approximately 0.01-2% of the level of hepatic microsomes of phenobarbital-induced rats. This brain activity was completely inhibited by anti P-450 b antibodies but was unaffected by anti P-450 c antibodies. As with hepatic P-450 b, metyrapone and chloramphenicol (100 microM) were good inhibitors of catalytic activity, whereas alpha-naphthoflavone (1 microM) was a poor inhibitor. No ETC O-deethylase activity was detectable in microsomes prepared from the pituitary glands of untreated rats. Upon pretreatment of rats with BNF, there was induction of ETC O-deethylase activity in the pituitary gland to a level of 3.3 +/- 1.5 pmol/min/mg of microsomal protein, but there was no significant increase in the level of activity in brain microsomes. Despite this, there was evidence of induction of P-450 c in both the brain and pituitary of BNF-pretreated rats since anti P-450 c antibodies inhibited brain activity by 55% and pituitary activity by 84%. The regional distribution of P-450 b and c in the hypothalamic-preoptic area and olfactory bulbs was examined. The level of ETC O-deethylase activity in the hypothalamic-preoptic area was not different from that in the whole brain, but in the olfactory bulbs activity was higher than that in whole brain, with a range of 0.1-52 pmol/min/mg of microsomal protein. The catalytic activity in the whole brain and in the olfactory bulbs was inhibited by anti P-450b but not by anti P-450c antibodies. Neither estradiol, testosterone, dehydrotestosterone, nor 5 alpha-androstane,3 beta,17 beta-diol (100 microM) competitively inhibited ETC O-deethylase activity, indicating that P-450 b is not responsible for the steroid hydroxylations previously reported in the brain. BNS pretreatment of rats did not cause a consistent increase in ETC O-deethylase upon BNF induction. However, there was an induction of P-450 c in the olfactory bulbs since catalytic activity was inhibited with anti P-450c antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)

7-Alkoxycoumarin O-Dealkylase↗

Ganglioside GM1 treatment prevents the effects of subacute exposure to toluene on N-[3H]propylnorapomorphine binding characteristics in rat striatal membranes.

The effects of ganglioside GM1 treatment (10 mg/kg, i.p., 3 days, once daily) were analyzed on N-[3H]propylnorapomorphine ([3H]NPA) binding characteristics in striatal membrane preparations from air or toluene (80 ppm, 3 days, 6 h/day) exposed adult male rats. It was found that toluene exposure induced increased Kd and Bmax values for [3H]NPA binding. These changes could be blocked by GM1 treatment, which by itself had no significant effects on the binding characteristics of [3H]NPA. The addition of toluene (9.3 mumol/ml) in vitro had similar effects on [3H]NPA binding characteristics as toluene exposure in vivo. These results indicate that the effects of toluene exposure on dopamine receptors are due to an alteration of membrane fluidity which is prevented by GM1 treatment.

Animals↗

The effect of fluoride and calcium on spinal bone mineral content: a controlled, prospective (3 years) study.

Daily treatment with 30 mg of sodium fluoride (NaF) and 1 g of calcium over a 3-year period increased the bone mineral content (BMC) in the spines of women (n = 25) with osteoporosis. Determination of the BMC was followed with dual photon absorptiometry (137Cs-241Am) in the third lumbar vertebra. No increase in BMC was found with only 10 mg sodium fluoride in combination with calcium (n = 25), with calcium alone (n = 25), or with placebo (n = 25). No serious side effects were registered. There was, however, minor gastrointestinal distress in one-fifth of the patients taking 30 mg NaF daily.

Aged↗

Species characteristics of the hepatic xenobiotic and steroid biotransformation systems of two teleost fish, Atlantic cod (Gadus morhua) and rainbow trout (Salmo gairdneri).

Groups of Atlantic cod and rainbow trout were treated (ip) with beta-naphthoflavone (BNF), phenobarbital, or peanut oil (controls), and properties of the hepatic xenobiotic and steroid metabolizing enzyme systems were evaluated. In both species, BNF treatment resulted in significant induction of microsomal 7-ethoxycoumarin O-deethylase, 7-ethoxyresorufin O-deethylase, biphenyl 4-hydroxylase, and phenanthrene oxidation, especially at the 1,2-position. Immunochemical studies with rabbit IgG prepared against the major BNF-inducible cytochrome P-450 in cod, P-450c, revealed increased amounts of immunoreactive protein in liver slices from both species after BNF treatment. The molecular weight of the induced protein was approximately 58,000 Da, as shown by Western blotting. When titrating biphenyl 4-hydroxylation, however, the antibodies distinguished between the two species, inhibiting the activity of BNF-induced cod 90% and that of rainbow trout 40% at 10 mg IgG/nmol P-450. Furthermore, cytochrome b5 content and UDP-glucuronyltransferase activity were significantly induced only in rainbow trout, whereas the specific content of cytochrome P-450 was significantly increased only in cod. Differences between the two species were observed in the levels of constitutive activities, the amount of induction, and in the regioselectivity of phenanthrene oxidation and androstenedione metabolism. Treatment with phenobarbital showed no effect on any of the parameters investigated in either species. The results show that although there are many common features of the hepatic xenobiotic and steroid biotransformation systems of the two teleosts, certain species characteristics exist in constitutive properties and induction responses.

7-Alkoxycoumarin O-Dealkylase↗

Growth hormone modifies the growth rate of enzyme-altered hepatic foci in male rats treated according to the resistant hepatocyte model.

Male and female Wistar rats were given an initiating i.p. injection of diethylnitrosamine (DEN; 200 mg/kg body wt). Two weeks later the rats were given a diet containing 0.02% (w/w) 2-acetylaminofluorene (2-AAF) for 2 weeks. In the middle of the 2-AAF treatment a 70% partial hepatectomy (PH) was performed. In order to identify the pituitary hormone responsible for the previously observed sex difference (male greater than female) in and influence of ectopic pituitary grafts on focal growth during 2-AAF/PH selection of enzyme-altered foci, male rats were treated with a continuous infusion of bovine growth hormone (bGH; 6 micrograms/h) or ovine prolactin (oPrl; 6 micrograms/h) by way of osmotic minipumps. Hormonal treatment was started 1 week after initiation and was finished 1 week after the 2-AAF selection period. All rats were killed 6 weeks after initiation and liver sections were stained for gamma-glutamyltransferase. The number of foci/cm2 as well as the area per focus and area ratio (mm2 foci/cm2 liver section) were calculated. Whereas no significant differences in the number of foci/cm2 were observed between the different groups of rats, bGH treatment of male rats decreased both the area/focus and the area ratio down to the female level. No significant effects were seen following oPrl administration when compared with control males. In vitro studies of subcellular preparations from the liver lobes obtained at PH showed that the sexually differentiated N-hydroxy-2-AAF sulfotransferase activity (male greater than female) in male rats was 'feminized', i.e. decreased, by bGH administration, but not by infusion of oPrl. The present investigation strengthens the view of growth hormone as an important determinant of sex differences in chemical carcinogenesis in rat liver, possibly via an influence on carcinogen metabolism.

2-Acetylaminofluorene↗

The loads on the lumbar spine during extreme weight lifting.

The load on the lumbar spine was calculated in eight power lifters when they executed an extremely heavy lift. The calculated load on L3 as well as the total load lifted during training in the last year were related to the bone mineral content (BMC) in the L3 as determined with dual photon absorptiometry. The loads on L3 in the lifters ranged between 18.8 and 36.4 kN. The BMC values were extremely high and closely correlated to the amount of weight lifted during training (r2 = 0.82). The study showed that intensive training will increase the BMC to an extent that the spine can tolerate extraordinary loads.

Adult↗

Effects of subacute treatment with toluene on cerebrocortical alpha- and beta-adrenergic receptors in the rat. Evidence for an increased number and a reduced affinity of beta-adrenergic receptors.

Subacute treatment with toluene (80-1500 p.p.m.) produces a dose-dependent reduction of affinity and increase in density of the beta-adrenergic antagonist [3H]dihydroalprenolol binding sites in the frontoparietal cortex of the male rat, while the binding characteristics of alpha 1-adrenergic ([3H]WB 4101) and alpha 2-adrenergic ([3H]p-aminoclonidine) binding sites in the same region is unaffected by this treatment as evaluated in vitro. Therefore, it is suggested that the cortical beta-adrenergic receptors are particularly vulnerable to the action of toluene in vivo. It is speculated that as a result cortical beta-adrenergic neurotransmission may be altered following exposure to low concentrations of toluene, possibly related to the physico-chemical properties of toluene, leading to changes in membrane fluidity.

Animals↗

Effects of subacute toluene exposure on protein phosphorylation levels in rat frontoparietal and striatal membranes.

Effects of subacute toluene exposure (80 p.p.m. toluene in air, 5 + 4 days, 6 h day-1) were analysed on calcium (Ca2+)- and cyclic adenosine monophosphate (cAMP)-induced protein phosphorylation levels in membrane preparations from the frontoparietal cortex and the striatum of the adult male rat. After protein separation by gel electrophoresis, the amount of radioactive phosphate incorporated from adenosine 5'-[gamma-32P] triphosphate, tetra-(ethylammonium) salt ([32P]ATP) was measured indirectly by autoradiography. The 21 most phosphorylated protein bands were then analysed by computerized image analysis. In the frontoparietal cortex no protein bands were significantly affected after cAMP-induced back phosphorylation, while after Ca2+ stimulation there was a decreased incorporation of [32P]ATP in a 22,000 protein band. In the striatum there was a reduced incorporation of [32P]ATP in a 26,000 protein band after cAMP-induced back phosphorylation, and in four bands of 20,000, 21,000, 52,000 and 134,000, respectively, after Ca2+ stimulation. The reduced incorporation of [32P]ATP in these proteins indicated increased original phosphorylation levels after toluene exposure. A comparison between the frontoparietal cortex and the striatum showed a selective vulnerability of phosphorylation processes in striatal membrane protein bands. In conclusion, toluene exposure at low doses augments membrane protein phosphorylation levels in the rat forebrain and especially in the striatum, probably leading to changes in information handling and/or metabolic changes.

Animals↗