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Biomedical subjects

A Fredriksson

Publications and source records attributed to A Fredriksson.

At least 55 records · Page 3Linked to original sources
PubMed1997

Clinical safety of enamel matrix derivative (EMDOGAIN) in the treatment of periodontal defects.

The aim of the present clinical trial was to test tolerability during 2 treatments with EMDOGAIN in a large number of patients. An open, controlled study design in 10 Swedish specialist clinics was chosen, with a test group of 107 patients treated with EMDOGAIN in connection with periodontal surgery at 2 surgical test sites per patient. The procedures were performed 2 to 6 weeks apart on one-rooted teeth with at least 4 mm deep intraosseous lesions. A control group of 33 patients underwent flap surgery without EMDOGAIN at 1 comparable site. In total, 214 test and 33 control surgeries were performed. Serum samples were obtained from test patients for analysis of total and specific antibody levels. 10 of the patients had samples taken before and after the first surgery, 56 other samples were taken after one treatment with EMDOGAIN, and 63 after 2 treatments. None of the samples, not even from allergy-prone patients after 2 treatments, indicated deviations from established baseline ranges. This indicates that the immunogenic potential of EMDOGAIN is extremely low when applied in conjunction with periodontal surgery. Comparison between the test and control groups demonstrated the same type and frequency of postsurgical experiences, i.e., reactions caused by the surgical procedure itself. Clinical probing and radiographic evaluation was performed at baseline and 8 months postsurgery. About half of the patients (44 test and 21 control) were also evaluated after 3 years. There was a significant difference between the test and control results at 8 months postsurgery, and this difference had increased further at the 3 year follow-up. The 2.5-3 mm increase in attachment and bone level after treatment with EMDOGAIN was of the same magnitude as seen in the studies with split-mouth design aiming for test of effectiveness of EMDOGAIN.

Adult↗
PubMed1995

Bioallethrin causes permanent changes in behavioural and muscarinic acetylcholine receptor variables in adult mice exposed neonatally to DDT.

We recently reported changes in the density of muscarinic acetylcholine receptors in cerebral cortex of mice treated neonatally with DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane) and receiving bioallethrin as adults. We also found behavioural aberrations in adult mice treated with bioallethrin, whether neonatally treated with DDT or the vehicle. To ascertain whether these changes were permanent, 10-day-old mice received an oral dose of DDT (0.5 mg/kg body weight) and at the age of 5 months they received bioallethrin orally (0.7 mg/kg body weight/day; 7 days). The animals were investigated at the age of 7 months. Here we report muscarinic acetylcholine receptor changes, additional behavioural disturbances and learning disabilities in mice receiving DDT as neonates and bioallethrin as adults, whereas the behavioural disturbances in mice receiving vehicle as neonates and bioallethrin as adults had diminished and changes in proportions of high- and low-affinity binding sites had developed. No changes in the density of nicotinic acetylcholine receptors were noted for any of the treated groups. In conclusion, exposure of neonates to DDT leads to increased susceptibility in adults to a short-acting pesticide with similar neurotoxic action. An adult exposure to this short-acting pesticide to mice neonatally exposed to DDT leads to irreversible muscarinic acetylcholine receptor changes and behavioural disturbances with additional changes 2 months after the exposure.

Allethrins↗
PubMed1995

Exposure to an organophosphate (DFP) during a defined period in neonatal life induces permanent changes in brain muscarinic receptors and behaviour in adult mice.

The organophosphate Diisopropylfluorophosphate (DFP) is a well-known inhibitor of cholinesterases. We have recently observed that neonatal exposure to a single subsymptomal dose of DFP induces permanent alterations in muscarinic cholinergic receptors (MAChRs) and in spontaneous behaviour, in the mice as adults. In order to determine if there is a critical period for these effects, neonatal mice were given a single oral dose of 1.5 mg/kg DFP b.wt. on postnatal day 3, 10 or 19, causing equal inhibition of AChE. At the adult age of 4 months the mice were tested for spontaneous motor behaviour, and were subsequently sacrificed for measurement of density of MAChRs and subpopulations of MAChRs in the cerebral cortex by using the antagonist quinuclidinyl benzilate ([3H]QNB), and agonist carbachol, respectively. At adult age, mice exposed to DFP on postnatal day (PND) 3 or 10 showed significant (P < or = 0.01) alterations in spontaneous motor behaviour and a significant (P < or = 0.01) decrease in muscarinic receptor density. There were no alterations mice exposed on PND 19. The proportions and affinity-constants of high- and low-affinity MAChR binding sites were not affected in mice showing altered MAChR density. The lack of effect on mice exposed on PND 19 was not due to differences in AChE activity.

Animals↗
PubMed1995

The effect of mercury vapour on cholinergic neurons in the fetal brain: studies on the expression of nerve growth factor and its low- and high-affinity receptors.

The effects of mercury vapour on the production of nerve growth factor during development have been examined. Pregnant rats were exposed to two different concentrations of mercury vapour during either embryonic days E6-E11 (early) or E13-E18 (late) in pregnancy, increasing the postnatal concentration of mercury in the brain from 1 ng/g tissue to 4 ng/g tissue (low-dose group) or 11 ng/g (high-dose group). The effect of this exposure in offspring was determined by looking at the NGF concentration at postnatal days 21 and 60 and comparing these levels to age-matched controls from sham-treated mothers. Changes in the expression of mRNA encoding NGF, the low- and high-affinity receptors for NGF (p75 and p140 trk, respectively) and choline acetyltransferase (ChAT) were also determined. When rats were exposed to high levels of mercury vapour during early embryonic development there was a significant (62%) increase in hippocampal NGF levels at P21 accompanied by a 50% decrease of NGF in the basal forebrain. The expression of NGF mRNA was found to be unaltered in the dentate gyrus. The expression of p75 mRNA was significantly decreased to 39% of control levels in the diagonal band of Broca (DB) and to approximately 50% in the medial septal nucleus (MS) whereas no alterations in the level of trk mRNA expression were detectable in the basal forebrain. ChAT mRNA was slightly decreased in the DB and MS, significantly in the striatum. These findings suggest that low levels of prenatal mercury vapour exposure can alter the levels of the NGF and its receptors, indicating neuronal damage and disturbed trophic regulations during development.

Animals↗
PubMed1995

Synergistic interactions between COMT-/MAO-inhibitors and L-Dopa in MPTP-treated mice.

Four experiments were performed to investigate the anti-akinesia effects of combining a sub-threshold dose (5 mg/kg, s.c.) of L-Dopa with different doses and combinations of COMT and MAO inhibitors upon the hypokinesia observed in MPTP-treated mice. Ro 40-7592 (1 and 3 mg/kg, s.c.), a novel COMT inhibitor, 60 min before L-Dopa reinstated both locomotion and rearing during a 2-hr interval after L-Dopa in MPTP mice; control mice were unaffected. The combination of Ro 40-7592 (3 mg/kg, s.c.) and pargyline (5 mg/kg, s.c.), a MAO inhibitor, with L-Dopa produced increases in both the peak effect and duration of action indicating a distinct potentiation of the effects of Ro 40-7592 by pargyline. L-Deprenyl, a MAOB inhibitor, together with L-Dopa, restored locomotion and rearing behaviour at all three doses applied (1, 3 and 10 mg/kg, s.c.); in control mice, motor activity was stimulated at the higher doses (3 and 10 mg/kg, s.c.), independent of L-Dopa administration. Combining L-Deprenyl (3 mg/kg, s.c.) with Ro 40-7592 (3 mg/kg, s.c.) one hr before L-Dopa to MPTP mice potentiated the restorative effects of each compound by itself, although no increase in peak effect was obtained. In the control mice, L-Deprenyl plus Ro 40-7592 or L-Deprenyl, by itself, stimulated motor activity following injection of L-Dopa. Marked dopamine (DA) depletions in the striatum of MPTP-treated mice were evident. The present results demonstrate that the effects of the COMT/MAO inhibitors in combination, and in conjunction with L-Dopa (at a dose that was without effect by itself), were well in excess of a summation of their individual effects. It was concluded therefore that a synergism of the restorative, anti-akinesic action of these compounds in MPTP-treated mice could offer a broader therapeutic spectrum in the treatment of Parkinson's disorder.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

Neonatal exposure to a type-I pyrethroid (bioallethrin) induces dose-response changes in brain muscarinic receptors and behaviour in neonatal and adult mice.

This study shows that neonatal exposure to the insecticide bioallethrin has a dose-dependent effect on muscarinic cholinergic receptors (MAChR) in the neonatal mouse, leading to permanent changes in MAChR and in spontaneous behaviour in adult mice. Neonatal NMRI mice, given oral doses of either bioallethrin or the vehicle, once daily between the 10th and 16th postnatal day, were killed at the age of 17 days or 1 week after the spontaneous motor behaviour tests at 4 months. The MAChR were assayed in the cerebral cortex by using the antagonist quinuclidinyl benzilate ([3H]QNB) and the agonist carbachol. In the 17-day-old mice bioallethrin exposure elicited a significant dose-dependent increase in the specific [3H]QNB binding. The competition study showed that the proportion of low-affinity binding was significantly increased in the 17-day-old mice compared with controls. In the adult mouse there was a significant dose-dependent decrease in specific [3H]QNB binding. In these adult mice the behavioural variables 'locomotion' and 'total activity' showed significant (P < or = 0.01) dose-dependent increases at all doses up to and including 0.70 mg/kg b.wt.

Aging↗
PubMed1994

MPTP-induced behavioural and biochemical deficits: a parametric analysis.

Two experiments were performed to study the parametric effects of long-term administration of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), as a functional model of parkinsonism in mice. The behavioural deficits induced by different doses of MPTP (5, 10, 20, 30 or 40 mg/kg, s.c., each injected on two occasions) at a 3-week or a 3-month treatment-testing interval were evidenced by significant reductions of spontaneous motor activity, from the 10 mg/kg dosages upwards at the 3-week interval and from 30-40 mg/kg at the 3-month interval. Significant dopamine (DA) reductions in the mouse striatum were obtained at these dose levels and intervals. The behavioural deficit of the 40 mg/kg dose (injected on two occasions) and tested at the 3-, 6-, 12-, 24- and 40-week intervals (separate as well as repeated testing groups) indicated marked and relatively comparable reductions of all three parameters of motor activity, locomotion, rearing and total activity. DA depletions were severe at all five test intervals. These results offer functional and neurochemical evidence that MPTP treatment produces permanent damage to the nigrostriatal motor system in mice.

Animals↗
PubMed1994

Synergistic interactions between NMDA-antagonists and L-dopa on activity in MPTP-treated mice.

Four experiments were performed to investigate whether or not coadministration of NMDA-antagonists potentiate the effect of an ineffective dose of L-Dopa on motor activity in hypoactive MPTP-treated mice. Motor activity was measured in an automated system recording both locomotion (horizontal) and rearing (vertical) activity. L-Dopa alone, at doses of 10 and 20 mg/kg, but not 5 mg/kg, expressed an anti-akinesia effect in MPTP-treated mice. The non-competitive NMDA-antagonist MK-801 (0.03, 0.1, and 0.3 mg/kg) increased by itself both locomotion (0.1 and 0.3 mg/kg) and rearing (0.03 mg/kg) in control (saline-treated) mice whereas no effect was seen in the MPTP-treated mice. Combined with 5 mg/kg L-Dopa, MK-801 (0.1 mg/kg) increased locomotion in MPTP-treated mice. There was no interaction seen between L-Dopa and MK 801 in the control mice. CGP40116 and CGP40117, the active D- and the inactive L-stereoisomer of the competitive NMDA-inhibitor CGP37849, respectively, were also administered together with 5 mg/kg L-Dopa. Both doses (0.003 and 0.03 mg/kg) of CGP40116 in contrast to CGP40117, produced anti-akinesia effect in MPTP-treated mice. CGP40116 (0.0001 to 0.1 mg/kg) together with 5 mg/kg L-Dopa did not affect behaviour in control mice but produced (0.01 mg/kg CGP40116 and 5 mg/kg L-Dopa) in the MPTP-treated mice an anti-akinesia effect. Our findings indicate that the non-competitive NMDA-antagonist MK-801, at doses with reported side-effects, only increase locomotion while rearing remained unaltered in MPTP-treated mice when combined with 5 mg/kg L-Dopa. Only the active stereoisomer CGP40116 in contrast to CG40117, at doses far below reported side-effects, dose-dependently modulated the anti-akinesia effect of a subthreshold dose of L-Dopa. Such data thus support the notion that this behavioural modulation was regulated via NMDA-receptors. The synergism between L-Dopa and the competitive NMDA-antagonist CGP40116 has a potential in treatment of Parkinson's disease to reduce the side-effects of doses of L-Dopa that are used today.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

Effects of D1 and D2 agonists on spontaneous motor activity in MPTP treated mice.

Two experiment were performed to study the effect of combining bromocriptine with SKF 38393 (SKF), or vice/versa, upon parameters of spontaneous motor activity in MPTP treated and saline (control) treated mice. Treatment with MPTP (2 x 40 mg/kg, subcutaneously) induced a hypoactive condition compared with saline treated mice. Bromocriptine (10 mg/kg, subcutaneously), administered to MPTP mice 2 hr, but not 1 or 4 hr, after SKF (6 mg/kg, subcutaneously) caused a marked increase in locomotion and rearing behaviour. The administration of bromocriptine (10 mg/kg, subcutaneously) 4 hr before SKF (6 mg/kg, subcutaneously) elevated all three parameters of spontaneous activity in the MPTP treated mice, independent of the injection of SKF. Bromocriptine injection 1 or 2 hr before SKF decreased locomotion in both MPTP and control mice. Neurochemical analysis confirmed the dopamine depletion in the MPTP treated mice. These results are discussed in terms of the reliability of the MPTP model of parkinsonism in mice and the dopamine D1/D2 receptor hypersensitivity following denervation with the neurotoxin.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Neonatal exposure to DDT induces increased susceptibility to pyrethroid (bioallethrin) exposure at adult age.--Changes in cholinergic muscarinic receptor and behavioural variables.

We have recently reported that DDT and the pyrethroid bioallethrin cause similar changes in the brain muscarinic cholinergic receptors (MAChR) and behavioural disturbances in the neonatal and adult mouse when given to neonatal mice during the peak of rapid brain growth. In the present study the interaction between neonatal and adult exposure to DDT and bioallethrin, respectively, is explored. Ten-day-old NMRI mice received a single low oral dose of DDT (0.5 mg/kg body wt). At adult age (5 months) the mice received bioallethrin 0.7 mg/kg body wt./day per os for 7 days. Mice used as controls received a 20% fat emulsion vehicle. The spontaneous behavioural tests revealed significant differences, both in mice treated neonatally with DDT and receiving bioallethrin as adults and in mice receiving the vehicle as neonates and bioallethrin as adults, compared with their corresponding controls. However, the behavioural changes developed in mutually opposite directions. Significant changes in MAChR, assayed in the P2 fraction of the cerebral cortex by using the muscarinic antagonist, quinuclidinyl benzilate ([3H]QNB) and agonist carbachol, was only observed in animals receiving DDT as neonates and bioallethrin as adults. The present study indicates an increased susceptibility in the cholinergic muscarinic receptors and a different behaviour reaction in animals already exposed to DDT (at a physiologically relevant dose), when again exposed to a similar neurotoxic agent as adults.

Administration, Oral↗
PubMed1993

Neonatal exposure to paraquat or MPTP induces permanent changes in striatum dopamine and behavior in adult mice.

We have recently reported that environmental toxicants, such as DDT, PCBs, pyrethroids, and nicotine can induce permanent functional and neurochemical changes in adult mice when given to neonatal mice during the peak of rapid brain growth. In the present investigation the neurotoxic effects following neonatal exposure to paraquat (N,N'-dimethyl-4,4'-bipyridylium), a broad-spectrum herbicide with structural similarity to the 1-methyl-4-phenylpyridium ion (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which can induce Parkinson's syndrome, and MPTP were studied. Five groups of mice were given paraquat or MPTP orally: group 1, vehicle; groups 2 and 3, MPTP 0.3 and 20 mg/kg; groups 4 and 5, paraquat 0.07 and 0.36 mg/kg when 10 and 11 days old. Neonatal spontaneous motor activity was tested on Day 18 in mice given paraquat 0.36 mg/kg body wt. Adult spontaneous motor activity testing was performed at ages 60 and 120 days. On Day 125 the mice were decapitated and the contents of dopamine (DA), serotonin (5-HT), and metabolites in striatum were analyzed. The results may be summarized as follows: (1) No signs of acute toxicity or differences in weight gain were observed in any of the groups. Nor was any respiratory distress or motor performance dysfunction evident on Day 18 in mice given paraquat 0.36 mg/kg body wt. (2) The behavioral tests at 60 days of age showed a marked hypoactive condition in the mice given paraquat (at both doses) and MPTP (at both doses). (3) At the age of 120 days the hypoactive behavior persisted and appeared even more pronounced. (4) The high doses of MPTP and paraquat--and to a less extent the low doses--reduced the striatal content of DA and metabolites without affecting 5-HT. The altered behavior, together with the dose-dependent reduction of DA and metabolites in neostriata in this study, further demonstrates the susceptibility to low-dose exposure to environmental pollutants during the neonatal period.

Animals↗
PubMed1993

Altered behaviour in adult mice orally exposed to tri- and tetrachloroethylene as neonates.

Male NMRI mice were orally exposed to trichloroethylene (TRI, 50 and 290 mg/kg per day) and tetrachloroethylene (PER, 5 and 320 mg/kg per day) between days 10 and 16 postnatally. Spontaneous activity, observed as locomotion, rearing and total activity, was measured over three 20-min periods at an age of 17 and 60 days. Compared to controls, mice at 17 days of age were unaffected, while at 60 days of age mice exposed to PER showed changes in all three spontaneous motor activity variables, while TRI-exposed mice only were affected in rearing. This indicates a neonatal susceptibility of brain maturation to these chlorinated organic solvents in achieving long-lasting changes in adult behaviour.

Administration, Oral↗
PubMed1993

Effects of maternal dietary supplementation with selenite on the postnatal development of rat offspring exposed to methyl mercury in utero.

Female Sprague-Dawley rats were fed a control standard diet or a selenite (Se) supplemented diet (1.3 p.p.m. Se) for 8 weeks before mating and during gestation and lactation. Blood glutathione peroxidase activity (GSH-Px) was measured as a biomarker of Se in dames. After mating, the females from two dietary groups were divided into three subgroups (6 groups with 10 animals in each) given 0 (vehicle), 2 or 6 mg/kg methyl mercury (MeHg) by gavage on days 6-9 of gestation. Day 2 post parturition all litters were standardized to 6 pups per litter and remaining pups were used for determination of blood and brain total Hg contents. Behavioural testing was performed at two months of age. The results of the study showed that supplementing the diet with Se partly antagonized some adverse effects of the MeHg such as hypoactivity especially in the high MeHg dose group. There were no changes in physical development or body weight except a tendency to decreased body weight in offspring of mothers exposed to 6 mg Hg/kg. The GSH-Px activity was significantly increased in animals fed on Se supplemented diet. The dietary Se supplementation resulted in considerably increased concentrations of mercury in the blood of the offspring despite milder signs of CNS toxicity and no increase in brain concentrations of mercury.

Animals↗
PubMed1993

Antibodies against papillomavirus antigens in cervical secretions from condyloma patients.

Samples of cervical secretions and serum from 30 women with genital condylomas and 30 age-matched controls were tested for the presence of immunoglobulin A (IgA) and IgG antibodies against a panel of papillomavirus-derived antigens. The same cervical samples were also analyzed for presence of human papillomavirus (HPV) DNA by Southern blotting and polymerase chain reaction. By Southern blotting HPV DNA was detected in 8 of 30 patients with condylomas and 2 of 30 controls, and by the polymerase chain reaction HPV DNA was detected in 14 of 30 patients with condylomas and 5 of 30 controls. A total of 18 of 29 patients with condylomas and 8 of 28 controls had IgA antibodies in cervical secretions to an E2 synthetic peptide, and 17 of 29 patients with condylomas and 5 of 28 controls had local IgA antibodies to an E7 peptide (P < 0.025 and P < 0.005, respectively). The results suggest that measurement of local antibody production against selected HPV antigens may be useful in the study of HPV immunology and, possibly, for the diagnosis of HPV infection.

Adolescent↗
PubMed1992

Exposure to DDT during a defined period in neonatal life induces permanent changes in brain muscarinic receptors and behaviour in adult mice.

DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] is a potent neurotoxicant in both vertebrate and invertebrate species. We have previously reported that neonatal exposure to DDT affects the muscarinic cholinergic receptors (MAChR) in the cerebral cortex in the neonatal mouse, leading to permanent disturbances in the cholinergic system and behaviour of the animals as adults. In order to determine if there is a critical period for these effects, mice at the ages of 3-days, 10-days and 19-days were given a single low oral dose of DDT (0.5 mg/kg b.wt.). At adult age (4 months) the mice were tested for spontaneous behaviour: 'locomotion', 'rearing' and 'total activity', and were subsequently sacrificed for measurement of the density of MAChR and subpopulations of MAChR in the cerebral cortex by using the muscarinic antagonist quinuclidinyl benzilate, [3H]QNB, and agonist carbachol, respectively. A significant increase in spontaneous motor behaviour and a significant decrease in MAChR density in the cerebral cortex was only observed in adult mice receiving DDT at the age of 10 days. The induction of these disturbances is limited to peaks in the development of spontaneous behavioural activity and MAChR in the neonatal rodent.

Animals↗
PubMed1992

Behavioural effects of neonatal metallic mercury exposure in rats.

The effect of neonatal exposure of rats to mercury vapour (Hg0), at the concentration 0.05 mg/m3, 1 h (low dose) or 4 h (high dose), on the behaviour in adulthood were studied. Exposure occurred on days 11-17 (the period of rapid brain growth). Tests for spontaneous motor activity were performed at the ages of 2 and 4 months. Rats exposed to the high dose Hg0 showed a marked increase in variables locomotion and total activity but a decrease for rearing when tested at 2 months of age. At 4 months of age these rats showed a marked hypoactivity with respect to all three variables. Rats exposed to the low dose showed no significant differences at 2 months compared to controls. However, at the age of 4 months the same pattern (increase in variables locomotion and total activity but a decrease for rearing) already noticed in the high dose group at 2 months was observed. In the spatial learning tasks applied, the radial arm maze and circular swim maze, neonatally exposed pups showed a retarded acquisition to the former, while there was no difference compared to controls in the latter. These data indicate that neonatal exposure to mercury vapour results in similar behaviour changes as reported from offspring prenatally exposed to mercury vapour or methylmercury. Furthermore, exposure for 1 week to concentrations around Swedish threshold values (TLV) for 1 or 4 h resulted in dose and age-related behavioural changes.

Age Factors↗
PubMed1992

Effects of (R)-8-OH-DPAT and the enantiomers of UH-301 on motor activities in the rat: antagonism of (R)-8-OH-DPAT-induced effects.

The effects of the enantiomers of 5-fluoro-8-hydroxy-2-(dipropylamino)tetralin, UH-301 and the potent 5-HT1A-receptor agonist (R)-8-hydroxy-2-(dipropylamino)tetralin, (R)-8-OH-DPAT, on locomotion, rearing and total activity were studied in rats. The experiments were performed as tests either of exploratory activity in non-habituated rats or of motor activity of rats habituated to the environment for 2 h before drug injection. (R)-8-OH-DPAT increased locomotion and total activity and decreased rearing in both conditions. (R)-UH-301 increased locomotion and slightly also total activity in habituated rats and decreased rearing in both conditions. (S)-UH-301 decreased locomotion and rearing in both conditions but only in doses of 10 mumol/kg and above. Lower doses of (S)-UH-301 (10 mumol/kg) antagonized (R)-8-OH-DPAT-induced increases of locomotion and total activity. As (S)-UH-301 decreased rearing, per se, it was not able to antagonize the (R)-8-OH-DPAT induced decrease. These results further support previous data that (S)-UH-301 is a 5-HT1A antagonist while (R)-UH-301 is a 5-HT1A agonist.

8-Hydroxy-2-(di-n-propylamino)tetralin↗