PubMed Health⌕ Search

Biomedical subjects

A Fredriksson

Publications and source records attributed to A Fredriksson.

At least 73 records · Page 4Linked to original sources

Diagnostic methods in the detection of prostate cancer: a study of a randomly selected population of 2,400 men.

We investigated the value of digital rectal examination, transrectal ultrasonography and prostatic specific antigen (PSA) analysis as aids in general clinical practice and in the early detection of prostate cancer. Of a randomly selected population of 2,400 men 55 to 70 years old who were offered examination with digital rectal examination, transrectal ultrasound and PSA analysis, 1,782 (74%) accepted and prostate cancer was detected in 65 (3.6%). When the transrectal ultrasound results were also considered the detection rate of digital rectal examination (2.3%) was increased by 50% and the number of stage T2A or less tumors was doubled. At reexamination due to markedly high PSA values (7 micrograms/l. or more) only a few additional cancers (5%) were detected. However, it is noteworthy that 80% of the detected cancers were found among the subgroup with abnormal PSA values (4 micrograms/l. or more) and comprising 17% of the study population, which suggests the possibility of selecting a risk group at mass screening. Moreover, the positive predictive value increased from 4% (when only digital rectal examination was positive) to 71% for the combination of positive digital rectal examination, positive transrectal ultrasound and an increased PSA concentration (that is 7 micrograms/l. or greater).

Aged↗

Functional changes implicating dopaminergic systems following perinatal treatments.

A series of experiments, involving diverse perinatal treatments of either rats or mice, have been performed in order to investigate the effects of these treatments upon certain selected spontaneous and learned behaviors in the laboratory. Rat dams were administered either metallic mercury, organic tin or neuroleptic compounds, and the offspring of these dams was studied with behavioral tests at adult ages, prenatal studies. Newborn rat pups were administered either 6-hydroxydopamine (6-OHDA) (at various doses), or metallic mercury and then tested at adult ages. Newborn mice were administered either metaclopramide, an antiemetic compound, or haloperidol, a neuroleptic compound, and tested for spontaneous and d-amphetamine induced activity as adults. The behavioral battery the rats were tested with consisted of measures of spontaneous motor activity, including locomotion/ambulation, rearing, and head dipping behaviors, and a parameter under which diverse behaviors were collected, total activity. Alterations to instrumental maze learning performance were studied through application of the spatial learning tasks: the radial arm maze and the circular swim maze. Possible changes in dopaminergic pathways were assessed by measuring the effects of perinatal treatments upon d-amphetamine-induced activity. It was shown that prenatal metallic mercury, organic tin and the neuroleptic compounds, haloperidol and remoxipride altered various parameters of spontaneous motor activity, retarded maze learning in the radial arm maze and potentiated d-amphetamine-induced activity. Metallic mercury rats were not subjected to the amphetamine test and remoxipride rats were not retarded according to the learning task. Postnatal metallic mercury, 6-OHDA, haloperidol and the antiemetic compound, metaclopramide, also altered spontaneous and d-amphetamine-induced activity as well as radial arm maze performance, excluding in this case haloperidol and metaclopramide. None of these treatments altered performance in the circular swim maze, except for 6-OHDA where doses inflicting severe depletions (greater than 85% depletion compared to control values) caused notable impairments. One tentative conclusion from the pattern of behavioral changes, generally in the absence of any measurable neurochemical changes, observed after these treatments is that the functional development of dopaminergic systems had, to a greater or lesser degree, been altered.

Animals↗

Neonatal nicotine exposure induces permanent changes in brain nicotinic receptors and behaviour in adult mice.

The effects of neonatal nicotine exposure on spontaneous and nicotine-induced behaviour in 4-month-old mice and on the development of brain nicotinic receptors were studied. The behaviour study showed that mice treated with nicotine 66 micrograms (-)nicotine base/kg body weight (bw) s.c. twice daily between 10 and 16 days postnatally displayed a hypoactive condition, whereas mice treated with saline displayed a hyperactive condition. When the nicotinic receptors in the brain cortex were analyzed, the displacement curves for [3H]nicotine(-)nicotine revealed an almost equal proportion of high- and low-affinity binding sites in 17-day-old mice, while the high-affinity sites predominated in 4-month-old mice, with affinity constants for both high- and low-affinity binding sites 10 times higher in 4-month-old mice than in 17-day-old-mice. A decrease in the number of nicotinic receptors was observed from day 17 to 4 months, mainly of the low-affinity nicotinic type. Interestingly, the displacement curves in neonatally nicotine-treated mice showed only one population of high-affinity binding sites in 17-day- and 4-month-old mice though the total binding sites in 4-month-old mice were the same for the neonatally nicotine-treated and saline-treated mice. These results indicate that neonatal nicotine treatment prevents the development of low-affinity nicotinic sites in the brain and this earlier exposure to nicotine induces a different behaviour response in adult animals to a test dose of nicotine. Days 10-16 postnatally appear to be a critical period for the effects of nicotine on the brain.

Aging↗

Neurotoxic effects of two different pyrethroids, bioallethrin and deltamethrin, on immature and adult mice: changes in behavioral and muscarinic receptor variables.

We have recently shown that two pyrethroids, bioallethrin and deltamethrin, affect muscarinic cholinergic receptors (MAChR) in the neonatal mouse brain when given to suckling mice during the period of rapid brain growth. Such early exposure to these pyrethroids can also lead to permanent changes in the MAChR and behavior in the mice as adults. In the present study, male NMRI mice were given bioallethrin (0.7 mg), deltamethrin (0.7 mg), or a 20% fat emulsion vehicle (10 ml) per kilogram of body weight per os once daily between the 10th and 16th postnatal day. The mice were subjected to behavioral tests upon reaching the age of 17 days and at 4 months. Within 1-2 weeks after the behavioral tests the mice were killed by decapitation and crude synaptosomal fractions (P2) were prepared from the cerebral cortex, hippocampus, and striatum. The densities of MAChR were assayed by measuring the amounts of quinuclidinyl benzilate ([3H]QNB) specifically bound in the P2 fraction. The proportions of high-affinity (HA) and low-affinity (LA) binding sites of MAChR were assayed in a displacement study using [3H]QNB/carbachol. The behavioral tests at an adult age of 4 months indicated a significant increase in spontaneous motor behavior in both bioallethrin- and deltamethrin-treated mice. There was also a significant decrease and a tendency toward a decrease in the density of MAChR in the cerebral cortex in mice receiving bioallethrin and deltamethrin, respectively. The proportions of HA- and LA-binding sites of MAChR were not changed. This study further supports that disturbances of the cholinergic system during rapid development in the neonatal mouse can lead to permanent changes in cholinergic and behavioral variables in the animals as adults.

Allethrins↗

Neonatal exposure to 3,3',4,4'-tetrachlorobiphenyl: changes in spontaneous behaviour and cholinergic muscarinic receptors in the adult mouse.

We have previously reported that 3,3',4,4'-tetrachlorobiphenyl (TCB) affects muscarinic cholinergic receptors (MAChR) in the neonatal mouse brain when given to suckling mice at the age of 10 days. As shown in the present study, such early exposure to TCB may also lead to a permanent change in the MAChR and disturbed behaviour of the mice as adults. Male NMRI mice were given two single oral doses of TCB, 0.41 or 41 mg/kg body wt, and a 20% fat emulsion vehicle (10 ml)/kg body wt. The behavioural test at adult age of 4 months indicated a significant change in spontaneous motor behaviour in the TCB-treated mice. In mice receiving the highest dose of TCB there was also a minor increase (5%), although significant, in the density of MAChR in the hippocampus, assayed by using the tritium-labeled muscarinic antagonist, quinuclidinyl benzilate [( 3H]QNB). As previously reported, this part of the brain was affected in the neonatal mouse, which shows that the cholinergic system during rapid development in the neonatal mouse brain is sensitive to disturbance. This may lead to permanent changes in the animals as adults, accompanied by behavioural changes.

Animals↗

Digital rectal examination versus transrectal ultrasound in detection of prostate cancer. Preliminary results from a study of a randomly selected population.

In a study of 2,400 randomly selected men (age 55-70 years) for early detection of prostate cancer the authors have compared the diagnostic value of digital rectal examination (DRE), transrectal ultrasound (TRUS) and prostate specific antigen (PSA). Altogether 62 prostate cancers were detected, corresponding to a detection rate of 3.5% but by use of DRE the detection rate was only 2.3%. The study showed that TRUS added significantly to the detection rate. If radical surgery is restricted to stages T1 and T2A, the combined use of DRE and TRUS detected twice as many cases fit for this treatment than DRE alone. The authors advocate randomized studies for evaluation of early radical treatment of prostate cancer. Before results of such studies have appeared they recommend methodological studies aimed at development and enhancement of the accuracy of the diagnostic tools.

Aged↗

Chronic neurochemical and behavioral changes in MPTP-lesioned C57BL/6 mice: a model for Parkinson's disease.

The long-term effect of the parkinsonism inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on pre- and postsynaptic structures of the nigrostriatal and mesolimbic dopamine (DA) system in adult C57BL/6 mice (2 x 40 mg/kg s.c.) was investigated using neurochemical and behavioral methods. It was found that MPTP induced a severe depletion of striatal DA levels (-80%) that persists for 4 weeks after treatment, with less severe effects in nucleus accumbens (-36%) and the olfactory tubercle (-52%). These depletions are associated with decreased tyrosine hydroxylase (TH) activity as determined in vivo and increased turnover of DA. MPTP treatment did not induce any change in the DA2-receptor as determined by [3H]spiperone binding or by two different behavioral tests, i.e. apomorphine-induced climbing and apomorphine-induced stereotypies. No significant weight loss during 4 weeks after MPTP was found. The spontaneous motor activity in these mice was profoundly and persistently depressed (-66%) as a result of the MPTP-induced DA denervation and the motor deficit was completely reversed by L-DOPA treatment. We suggest that MPTP-treated C57BL/6 mice may serve as a suitable model for Parkinson's disease.

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

Altered behaviour in adult mice exposed to a single low dose of DDT and its fatty acid conjugate as neonates.

DDT, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane is one of the best-known insecticides which produces neurotoxic syndrome in mammals. DDT is also a world-wide environmental contaminant which is still used in several countries. We have previously reported on pronounced retention of DDT in the neonatal mouse brain. We have also observed that DDT and a DDT metabolite, DDOH, conjugated to palmitic acid (DDOH-PA), which have been found in DDT-treated female rats, affect the muscarinic cholinergic receptors in the brain of the neonatal mouse. We now report that neonatal exposure to a single low oral dose of DDT and DDOH-PA (1.4 mumol/kg b.wt.) also can lead to a permanent hyperactive condition in the mice as adults.

Animals↗

[Preventive antibiotics in emergency cesarean section. A prospective comparison of benzylpenicillin and ampicillin plus cloxacillin].

Emergency cesarean section, especially when performed more than ten hours after rupture of the membranes, involves a high risk of postoperative infection. Different antibiotic regimens have been shown to reduce these infections substantially. In this prospective study a combination of ampicilling (2 g) plus kloxacillin (2 g) given as a single-dose infusion directly after division of the cord reduced the post-operative infection rate to 13% in a group of high-risk emergency cesarean section cases. Benzylpenicillin only (2 g) was less efficient. No side-effects were observed, and this prophylaxis may have certain advantages over cephalosporins, especially with respect to enterococcus-induced endometritis.

Ampicillin↗

MPTP-induced hypoactivity in mice: reversal by L-dopa.

Three experiments were performed to study the subchronic effects of treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 2 x 40 mg/kg subcutaneously two weeks before testing) in C57 BL/6 mice upon spontaneous motor activity and the reversal of the long-term behavioural changes by acute treatment with L-Dopa. Mice treated with MPTP showed a drastic reduction of striatal dopamine levels (-88%) associated with reductions of all three parameters of spontaneous motor activity, i.e. locomotion, rearing and total activity, during both the initial, exploratory, stage (first 90 min), and later stages of the 3- or 4-hr test periods. L-Dopa (5-80 mg/kg subcutaneously) injected 60 min. after the start of testing dose-dependently improved all three parameters studied in MPTP treated mice with 10 mg/kg being the lowest dose causing a significant effect, while doses above 20 mg/kg caused hyperactivity. During the initial period, rearing activity in MPTP mice was to a variable degree suppressed by the L-Dopa treatment (20-80 mg/kg); these reductions were followed by enormous increases in motor activity by the 40 mg/kg (locomotion) and 80 mg/kg (total activity) L-Dopa groups. Both the degree and duration of the L-Dopa-induced hypoactivity for locomotor behaviour increased dose-dependently in control mice. No suppressive effects of L-Dopa were obtained for total activity in control mice, although the 80 mg/kg L-Dopa doses evoked hyperactivity for up to 90 min. following treatment for both locomotion and total activity.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Neonatal exposure to DDT and its fatty acid conjugate: effects on cholinergic and behavioural variables in the adult mouse.

We have recently observed that DDT and a DDT metabolite, DDOH, conjugated to a fatty acid, palmitic acid, DDOH-PA, affects muscarinic cholinergic receptors (MAChR) in the neonatal mouse brain when given to suckling mice during rapid brain growth. This early exposure of the neonatal mouse also affects the behaviour of the animals as adults. When DDT and DDOH-PA was given as a single low oral dose of 1.4 mumol/kg body weight, DDT (0.5 mg), DDOH-PA (0.7 mg) and a 20% fat emulsion vehicle (10 ml) per kg body weight to 10-day-old NMRI mice, behavioural tests at adult age of four months, indicated disruption of a simple, non-associative learning process, i.e. habituation, in both DDT and DDOH-PA treated mice. There was also a significant increase in the potassium evoked release of ACh from slices of cerebral cortex and a tendency towards a decrease in the density of MAChR in mice receiving DDT. These effects in the adult mice could not be correlated to the concentration of DDT in the adult brain since DDT one month after its administration to the 10-day-old mouse no longer is present in the brain.

Animals↗

Selective lesion of central dopamine or noradrenaline neuron systems in the neonatal rat: motor behavior and monoamine alterations at adult stage.

Different parameters of motor behavior (locomotion, rearing and total activity counts) were studied in the adult rat following neonatal intracisternal 6-hydroxydopamine (6-OHDA, 50 micrograms) treatment combined with noradrenaline (NA) uptake blocker (desipramine) or dopamine (DA) uptake blockers (amfolenic acid or GBR 12909) to obtain selective DA or NA lesions respectively. At 61-65 days of age, selective DA-lesioned animals showed an initial decrease in spontaneous motor behavior at test days 1 and/or 2, while at test days 4 and 5 hyperactivity was observed. However, following amfolenic acid or GBR 12909 pretreatment leading to a selective NA lesion, no difference in spontaneous motor behavior was seen on any of the 5 test days. Determination of regional brain levels of NA and DA confirmed the type of lesion predicted from the various pretreatments with selective uptake blockers. These data suggest that changes in motor behavior in the adult rats, following neonatal 6-OHDA treatment, are specifically related to a DA-denervation, whereas an NA lesion does not seem to influence the spontaneous motor behavior. However, following the selective DA lesion, significant increases of serotonin levels in striatum and cerebellum were observed, while following selective NA lesions an increase of cerebellar NA levels was found concomitant with drastic reductions of NA levels in frontal cortex and spinal cord.

Aging↗

Effects of d-amphetamine and methylphenidate on hyperactivity produced by neonatal 6-hydroxydopamine treatment.

Neonatal intracisternal administration of 6-hydroxydopamine (6-OHDA, 50 micrograms on day 1 after birth) caused a marked hyperactivity when the rats were tested as adults. These rats also showed severe DA depletions in striatum and nucleus accumbens. Pretreatment with the noradrenaline (NA) uptake inhibitor desipramine provided protection against NA depletion in frontal cortex and nucleus accumbens. Pretreatment with DA uptake inhibitors, amfolenic acid or GBR 12909, before 6-OHDA, provided full protection against DA depletion but produced marked NA depletion in frontal cortex. These rats did not demonstrate any degree of hyperactivity. Low doses of d-amphetamine (0.25 mg/kg SC) or methylphenidate (1 mg/kg SC) reversed the hyperactivity in DA-depleted rats but increased motor activity in vehicle-treated and NA-depleted rats. Higher doses of d-amphetamine (1 mg/kg) or methylphenidate (4 mg/kg) produced potentiated levels of locomotion but attenuated levels of rearing in DA-depleted animals. The results further suggest the utility of the neonatal DA lesion in rats as a potential animal model for derivation of therapeutic agents that may be efficacious in the treatment of the hyperkinetic syndrome.

Animals↗

Neonatal 6-hydroxydopamine-induced dopamine depletions: motor activity and performance in maze learning.

Three experiments were performed to study the effect of dopamine (DA) depletions, induced by neonatal intracerebroventricular (ICV) treatment with 6-hydroxydopamine (6-OHDA), upon measures of spontaneous motor activity. Instrumental learning for food reward in an Olton radial arm maze and escape learning from a large, circular water maze were studied also. Motor activity was measured by direct observation of rats in a modified radial arm maze and by use of automated test cages equipped with photocell devices. 6-OHDA-treated rats demonstrated considerable and long-lasting locomotor (ambulation) activity and total activity increases. 6-OHDA-treated rats showed notably less rearing activity than the vehicle-treated rats during the initial 20 min of each 60-min test period. However, over the second half of these 60-min test periods, the 6-OHDA-treated rats demonstrated significantly more rearing activity than the vehicle-treated rats. In the acquisition of the running response, to obtain the 8 food pellets placed in each of the 8 arms of the radial arm maze, 6-OHDA rats showed a retarded acquisition, as measured by the latency and number of arms visited to acquire all eight pellets. 6-OHDA-treated rats failed completely to acquire the Morris-type swim maze task by which they were required to locate a platform just under the water surface in a circular water tank. The neurochemical assays indicated severe DA depletion in several forebrain regions. The present findings add to existing indications of the potential of this DA depletion condition as an animal model of the minimal brain dysfunction syndrome.

Animals↗

Prenatal methylazoxymethanol treatment potentiates d-amphetamine- and methylphenidate-induced motor activity in male and female rats.

The effects of the stimulant drugs, d-amphetamine and methylphenidate, upon the motor activity of male and female off-spring of pregnant rats, treated on gestation day 15 with the antimitotic agent methylazoxymethanol (MAM, 25 mg/kg) were studied in four experiments. Cortical and striatal hypoplasia induced by prenatal administration of MAM resulted in increased concentrations of catecholamines in those regions. Administration of d-amphetamine and methylphenidate caused significant increases in motor activity; this effect was markedly potentiated in the MAM-treated rats, both the male and female off-spring. Thus, the locomotion and total activity parameters showed similar, but not identical, drastic increases in behaviour induced by the stimulant drugs as a result of the prenatal MAM treatment whereas for the rearing parameter a lesser potentiation by the MAM treatment was observed. This potentiation of the excitatory effects of the stimulant compounds upon the behavioural parameters is interpreted in terms of a relative increase in the density of catecholaminergic terminals in the forebrain regions of the central nervous system. The present results are discussed with regard to the utility of prenatal MAM treatment as a possible animal model for certain neurological disorders.

Animals↗