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Biomedical subjects

L Löfberg

Publications and source records attributed to L Löfberg.

At least 19 recordsLinked to original sources
PubMed1999

Interindividual differences in hepatic expression of CYP3A4: relationship to genetic polymorphism in the 5'-upstream regulatory region.

Cytochrome P450 3A4, the most abundant P450 form in human liver, exhibits a very broad substrate specificity and is of great importance for drug metabolism. The interindividual difference in the hepatic expression of CYP3A4 is considerable. In order to investigate possible genetic factor(s) causing this variation, the rate of 6beta-hydroxylation of testosterone in human liver microsomes prepared from 46 different human liver samples was determined and the 5'upstream region (+10 to -490 bp) was sequenced from genomic DNA isolated from 39 of these livers. We found a 31-fold variation of the testosterone hydroxylase activity between the samples. However, a very high sequence homology between the CYP3A4 5'-upstream regions sequenced from the 78 different alleles was found. In fact, only three variant nucleotide exchanges were identified, all causing a -290 A-->G mutation (CYP3A4-V) in a so called nifedipine specific element (NFSE). The importance of this element and the polymorphism was evaluated by gel shift analysis. Competition experiments revealed that the binding of nuclear proteins, although having lower affinity to the CYP3A4-V form of the element, was unspecific in nature. In accordance, no influence of this polymorphism was seen on the microsomal testosterone hydroxylase activity in vitro. It is concluded that the promoter region of CYP3A4 is highly conserved, the only polymorphism being in the NFSE, which however does not influence the enzyme expression in liver to a significant degree. This casts doubt of a previously described relationship between the CYP3A4-V allele and cancer in the prostate and leukaemia.

Adolescent↗
PubMed1998

Acupuncture for pain relief during childbirth.

BACKGROUND: There are few studies on acupuncture in childbirth despite the generally established analgesic effect of acupuncture treatment. METHODS: The analgesic effect of acupuncture during childbirth was assessed by comparing the need for other pain treatments (epidural analgesia using bupivacaine, pudendal nerve block, intramuscular meperidine, nitrous oxide/oxygen, intracutaneous sterile water injections) in 90 women given acupuncture (acupuncture group) with that in 90 women not given acupuncture (control group). RESULTS: 52 women (58%) in the acupuncture group and 13 (14%) in the control group managed their deliveries without further pain treatment (p < 0.001). The groups were similar with respect to age, pariety, duration of delivery, use of oxytocine and incidence of Caesarean section. Acupuncture treatment was found to have no major side effects, and 85 women (94%) given acupuncture reported that they would reconsider acupuncture in future deliveries. CONCLUSION: Acupuncture reduces the need for other methods of analgesia in childbirth.

Acupuncture Therapy↗
PubMed1994

Intracerebral infusion of (+)-AJ76 and (+)-UH232: effects on dopamine release and metabolism in vivo.

The dopamine D3- and autoreceptor preferring antagonists (+)-AJ76 and (+)-UH232 were administered locally in the striatum and the nucleus accumbens. Their effects on dialysate dopamine and 3,4-di-hydroxyphenylacetic acid (DOPAC) were measured and compared with the effects of raclopride. (+)-AJ76 and (+)-UH232 but not raclopride seem to interact primarily with dopamine receptors in the terminal regions of the A9 and A10 dopaminergic fibers to exert their maximal effect on dopamine release in vivo. Thus, (+)-AJ76 and (+)-UH232 seem to recruit different dopamine receptor populations as compared to raclopride. Though the dopamine receptor antagonist-induced effects on dopamine release seem to be mediated mainly by dopamine receptors in the terminal areas, the effects on DOPAC by the different antagonists seem to be mediated mainly via effects elsewhere, presumably at the somatodendritic autoreceptors. Thus, it is suggested that the regulation of extracellular dopamine and DOPAC after treatment with dopamine receptor antagonists are subjected to different control mechanisms.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Differential effects of dopamine D2 and D3 receptor antagonists in regard to dopamine release, in vivo receptor displacement and behaviour.

To establish possible functional differences between the dopamine D2 and D3 receptor we investigated the relation between the ability, for a set of nine mixed dopamine D2 and D3 receptor antagonists, to displace N, N-dipropyl-2-amino-5,6-dihydroxy tetralin (DP-5,6-ADTN) from striatal binding sites and the subsequent behavioural consequences in vivo. Dopamine D2 receptor preferring antagonists are powerful displacers of DP-5,6-ADTN from the striatum. Maximal displacement is followed by strong hypomotility. Displacement of the agonist by the D3 preferring antagonist U99194A is only partial and results in synergistic increases in locomotor activity. Superimposing haloperidol upon GBR12909 leads to a synergistic increase in striatal dialysate dopamine concentrations. This effect is absent when combining GBR12909 with the putative D3 antagonist U99194A. These data give support for the hypothesis that the dopamine D3 receptor is functionally relevant at the postsynaptic level. Here, in contrast to the D2 receptor, it is proposed to exert an inhibitory influence on psychomotor functions.

Animals↗
PubMed1993

The dopamine D3 receptor and autoreceptor preferring antagonists (+)-AJ76 and (+)-UH232; a microdialysis study.

The in vivo neurochemical profiles of haloperidol, raclopride and the dopamine D3 and autoreceptor preferring dopamine receptor antagonists (+)-UH232 and (+)-AJ76 on dopamine release and metabolism in the dorsal striatum and in the nucleus accumbens are described. It is shown that both (+)-UH232 and especially (+)-AJ76 have different effects on brain dialysate dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) as compared to haloperidol or raclopride. It is suggested that the relative increase in dialysate dopamine over the relative increase in DOPAC is a neurochemical fingerprint, unique for different dopamine receptor antagonists. As a consequence the increased release and metabolism of dopamine after systemic administration of dopamine receptor antagonists may be controlled by different receptors and different dopamine antagonists can partly distinguish between these receptors. This may be due to their different interactions with different dopamine D2 type receptors. It is finally concluded that (+)-UH232 and especially (+)-AJ76 seem to prefer release regulating autoreceptors at the level of the axon terminals.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Dopamine receptors, controlling dopamine levels in rat adrenal glands-comparison with central dopaminergic autoreceptors.

Previous work in this laboratory, as well as observations reported in the literature, indicate that the adrenal medulla contains dopamine (DA) receptors of the D-2 subtype, which among other things are capable of controlling the DA level in rat adrenal glands. To further characterize the DA receptors involved in the control of the adrenal DA level, the effects of 9 DA receptor agonists with various intrinsic activities were compared. After various periods of drug administration the rats were killed by decapitation and the DA content of the adrenal glands and the DOPAC content of the forebrain were measured by high-performance liquid chromatography with electrochemical detection. All the investigated DA receptors agonists caused an increase in adrenal DA level, although statistical significance was not reached in one case [(-)-HW 165]. Domperidone, a DA D-2 receptor antagonist which does not readily cross the blood brain barrier, blocked the DA-elevating effects of apomorphine, quinpirole, B-HT 920 and both enantiomers of 3-PPP. For the two ergolines terguride and SDZ 208-920 the blockade by domperidone was not complete, suggesting that their effects are mediated not only through DA, but also through other receptor systems. The dose of domperidone used (3 mg/kg) had but a marginal influence on brain DOPAC levels, supporting the almost exclusively peripheral effect of this agent. Our data indicate that the DA D-2 receptors which control the DA level in the adrenal medulla in rats, have characteristics similar to, though not identical with the autoreceptors in the forebrain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

The effects of 6-OHDA-induced dopamine depletions in the ventral or dorsal striatum on maternal and sexual behavior in the female rat.

The effects of dopamine-depleting 6-OHDA infusions in the ventral or dorsal striatum on maternal and sexual behaviors were examined in female rats. Like sham-operated controls, lactating rats receiving 6-OHDA in the ventral striatum built good nests, nursed the infants and showed maternal aggression toward strange intruders. By contrast, the lesioned females performed poorly in tests for pup retrieval, as reflected in greatly protracted retrieval latencies. There was no effect of ventral striatal DA depletions on proceptive and receptive elements of female sexual behavior, which was studied after lactation following ovariectomy and exogenous administration of ovarian hormones, but these animals did show an attenuated hyperactivity response to a low dose of amphetamine. Females with dopamine lesions in the dorsal striatum did not differ from controls with respect to maternal and sexual behavior, but they did show an enhanced hyperactivity response to amphetamine treatment.

Amphetamine↗
PubMed1991

Mesotelencephalic dopamine system and reproductive behavior in the female rat: effects of ventral tegmental 6-hydroxydopamine lesions on maternal and sexual responsiveness.

The effects of lesions to the mesolimbic dopamine system on maternal and sexual behaviors in the female rat was assessed. Rat dams that were given ventral tegmental area microinfusions of 6-hydroxydopamine (6-OHDA) during lactation showed a persistent deficit in pup retrieval but were not impaired with respect to nursing, nest building, or maternal aggression. In addition, 6-OHDA-lesioned females failed to respond to amphetamine by showing locomotor hyperactivity. Administration of the dopamine blocker raclopride to neurologically intact dams also inhibited pup retrieval but had no effect on nursing. Females given 6-OHDA during pregnancy appeared completely unresponsive to pups, whereas no maternal deficits were seen in females that received 6-OHDA 8 weeks before parturition. Proceptive (hopping and darting) and receptive (lordosis) components of sexual behavior, assessed after ovariectomy and exogenous steroid hormone treatment, were not affected by mesolimbic 6-OHDA lesions.

Animals↗
PubMed1990

Increased dopamine release by the autoreceptor antagonist (+)-AJ 76 is Ca2(+)-dependent.

The effects of the preferential autoreceptor antagonist (+)-AJ 76 on dopamine release and metabolism were studied in the brain microdialysis model. The Ca2+ dependence of the effects of (+)-AJ 76 and d-amphetamine were compared. We found that (+)-AJ 76 increased the release and metabolism of dopamine and that the release was saturable. The release of dopamine by (+)-AJ 76 was dependent on extracellular Ca2+. However, the effects of (+)-AJ 76 on dopamine metabolism were independent of extracellular Ca2+. The effects of d-amphetamine on dopamine release and metabolism were independent of Ca2+. We conclude that the dopamine released by (+)-AJ 76 is dependent on neuronal impulse flow and that the dopamine released is of vesicular origin. The effects on dopamine metabolism and release may be exerted via different mechanisms. In contrast, the release and metabolism of dopamine by d-amphetamine were independent of impulse flow and extracellular Ca2+. We suggest that (+)-AJ 76 and d-amphetamine release dopamine from different pools.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Acute changes in dopamine levels in rat adrenal glands after administration of dopamine receptor agonists and antagonists.

The study was aimed at in vivo pharmacological identification of the possible dopamine (DA) receptor(s) involved in changes of the DA level in rat adrenal glands. Previous work in this laboratory has shown that the DA level is largely controlled by the rate of catecholamine synthesis. The rats were killed by decapitation after various periods of drug administration and the catecholamine content of adrenal glands and forebrain was measured by high-performance liquid chromatography with electrochemical detection. Administration of the DA D-1 + D-2 receptor agonist, apomorphine, induced a statistically significant increase in DA levels in the adrenal glands. The same effect was noted after administration of the DA D-2 receptor agonist, quinpirole. The DA D-2 receptor antagonist, raclopride, blocked the apomorphine-induced increase in adrenal DA levels but had no effect per se on these levels. The DA D-1 receptor agonist, SKF 38393, and the DA D-1 receptor antagonist, SCH 23390, did not have any effect on apomorphine-induced changes in DA content in the adrenals. The DA elevating effect of the DA D-2 receptor agonist, quinpirole, in the adrenals was completely blocked by the DA D-2 receptor antagonist, domperidone. This compound does not cross the blood-brain barrier readily and is thus supposed to act mainly on peripheral tissues. In support of this, the dose of domperidone used did not affect brain DOPAC levels. Our data, together with observations reported in the literature, indicate that the adrenal medulla contains DA receptors of the D-2 subtype, which are capable of controlling the DA level in rat adrenal glands.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1985

Direct-vision sampling of chorionic villi during extra-amniotic instillation of physiologic saline solution: effect on intrauterine pressure and fetal heart activity.

After 150 ml of physiologic saline solution had been infused into the extra-amniotic space before first-trimester vacuum aspiration abortion, intrauterine pressure ranged between 16 and 23 mm Hg, thus not more than during Braxton Hicks contractions. At chorionic villi sampling during continuous saline solution infusion, fetal heart activity (beats per 15 seconds) decreased temporarily from about 36 to about 33.

Amnion↗
PubMed1985

In vivo displacement by 3-PPP enantiomers of N,N-dipropyl-5,6-ADTN from dopamine receptor-binding sites in rat striatum.

The enantiomers of 3-PPP or haloperidol were injected in various doses to rats 1 hour after the established dopamine receptor ligand N,N-dipropyl-5,6-ADTN. After another 40 minutes the binding of the ligand to the striatum was measured by high performance liquid chromatography, using the level in the cerebellum as "blank". (-)-3-PPP was found to cause a maximum 71% displacement of the ligand from the striatal binding sites. Haloperidol proved to be more potent but not significantly more efficacious in displacing the ligand. However, the combined treatment with (-)-3-PPP and haloperidol caused a stronger displacement of the ligand than (-)-3-PPP alone, suggesting that the binding-site populations available for the two agents are not fully identical. (+)-3-PPP also caused displacement of the ligand but was considerably less potent than its enantiomeric twin. The results are discussed against the background of the different pharmacological profiles of the 3-PPP enantiomers and haloperidol. It is suggested that an inverse relationship may exist between receptor affinity and intrinsic activity and that such a relationship may be inherent in the mechanism underlying receptor stimulation.

Animals↗
PubMed1984

First-trimester diagnosis on chorionic villi obtained by direct vision technique.

An improved technique for direct vision chorionic biopsy that gives a clear view of the amniotic sac was developed. With this technique, used in 48 women prior to vacuum aspiration and in six cases for diagnosis (karyotyping or enzyme analysis), it was possible to obtain chorionic villi free from contamination by maternal tissue. It was also possible to pick out villi (rich in blood vessels and with abundant buds on their surface) found to be most capable of growing in vitro. In the diagnostic cases, the pregnancies have continued uneventfully since the sampling; one pregnancy is now in the 32nd week.

Adult↗
PubMed1984

"Blind" versus direct vision technique for fetal skin sampling in cases for prenatal diagnosis.

Seven fetuses at risk of developing a serious inherited skin disorder (epidermolysis bullosa atrophicans generalisata gravis in 4, bullous ichthyosiform erythroderma in 2, and non-bullous ichthyosiform erythroderma in 1) were subjected to prenatal diagnosis by fetal skin sampling. The conventional "blind" biopsy procedure was used in the first 3 cases; a two-cannula technique (one cannula for the optic instrument and the other for the biopsy forceps) that permits biopsy of the skin under direct vision, was employed in the remaining 4 cases. With the "blind" technique, 8 to 10 biopsy specimens had to be taken to ensure that enough skin material would be available for the microscopic examination; only one specimen out of every two was found to consist of skin; the remainder comprised fetal membranes, myometrium, or trophoblast. In one case where the "blind" procedure has been used, leakage of amniotic fluid occurred and labor started in the 33rd week. With the two-cannula technique, the number of biopsy samples could be confined to two or three, and all proved to be of skin.

Biopsy↗
PubMed1983

Fetal muscle biopsy.

Fetal muscle specimens suitable for histological and histochemical studies were obtained under fetoscopic visualization by removing a small piece of skin, thereby exposing the underlying muscle. The procedure was carried out in 7 cases prior to second-trimester abortion. Muscle specimens so obtained may become useful in the prenatal diagnosis of Duchenne muscular dystrophy.

Female↗
PubMed1983

Prenatal exclusion of Herlitz syndrome by electron microscopy of fetal skin biopsies obtained at fetoscopy.

Two women had each borne a child who had died of Herlitz syndrome, i.e., epidermolysis bullosa atrophicans generalisata gravis. In subsequent pregnancies, the women requested prenatal diagnosis. Samples of skin from the two fetuses were obtained at fetoscopy in the 19th week of gestation. In both cases the disorder could be ruled out prenatally on the basis of ultrastructural demonstration of the regular presence of normal hemidesmosomes with well-developed sub-basal dense plates at the dermo-epidermal junction. The infants were subsequently born and had normal skin, the sites of fetal skin biopsies showing no scarring.

Epidermolysis Bullosa↗
PubMed1982

Technical difficulties in fetal skin sampling.

Attempts were made to obtain skin biopsies from the fetuses of 18 women in the 16th to 21st week of gestation. In four of them the purpose was prenatal diagnosis because of the risk that the fetus might be affected with a severe skin disorder; the remaining women were to undergo elective abortion by hysterotomy. In the first 13 cases the conventional "blind" biopsy procedure was used. Of 71 biopsy specimens obtained with this technique, only one out of every three consisted of skin; the remainder comprised fetal membranes, myometrium, or trophoblast. In one of the diagnostic cases where the "blind" procedure was used, inadvertent removal of tissue specimens from the amniotic sac was probably responsible for the intermittent leakage of amniotic fluid that occurred in this woman from the 26th week of gestation and for the premature delivery in the 33rd week. In the remaining five women (including one for diagnosis), a two-cannula procedure was employed (one cannula for the optic instrument and the other for the biopsy forceps), permitting biopsy of the skin under direct vision. All the biopsy specimens taken by this method consisted of skin.

Biopsy↗