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Biomedical subjects

M Löfgren

Publications and source records attributed to M Löfgren.

At least 19 recordsLinked to original sources

Tolerance development to Morris water maze test impairments induced by acute allopregnanolone.

The progesterone metabolite allopregnanolone, like benzodiazepines, reduces learning and impairs memory in rats. Both substances act as GABA agonists at the GABA-A receptor and impair the performance in the Morris water maze test. Women are during the menstrual cycle, pregnancy, and during hormone replacement therapy exposed to allopregnanolone or allopregnanolone-like substances for extended periods. Long-term benzodiazepine treatment can cause tolerance against benzodiazepine-induced learning impairments. In this study we evaluated whether a corresponding allopregnanolone tolerance develops in rats. Adult male Wistar rats were pretreated for 3 days with i.v. allopregnanolone injections (2 mg/kg) one or two times a day, or for 7 days with allopregnanolone injections 20 mg/kg intraperitoneally, twice a day. Thereafter the rats were tested in the Morris water maze for 5 days and compared with relevant controls. Rats pretreated with allopregnanolone twice a day had decreased escape latency, path length and thigmotaxis compared with the acute allopregnanolone group that was pretreated with vehicle. Pretreatment for 7 days resulted in learning of the platform position. However, the memory of the platform position was in these tolerant rats not as strong as in controls only given vehicle. Allopregnanolone treatment was therefore seen to induce a partial tolerance against acute allopregnanolone effects in the Morris water maze.

Analysis of Variance↗

Early interdisciplinary rehabilitation programme for whiplash associated disorders.

PURPOSE: To assess the clinical outcomes of a multidisciplinary rehabilitation programme for early intervention of chronic whiplash associated disorders (WAD). The primary aim of the programme was to increase levels of activity and independence in patients suffering WAD. METHODS: Ninety subjects with purported chronic symptoms associated with whiplash associated disorder (WAD) were referred to a multi-centre multi-modal 5- and 8-week rehabilitation programme in 1997-1998, during which prospective and retrospective functional and psychological evaluations were conducted, the follow-up was to 6 months. RESULTS: Subjects indicated they were satisfied with the programme. Retrospective evaluation indicated increased ability to cope with and control pain and, to some extent, psychological aspects. The pain intensity in the neck and upper back were significantly decreased at 6 months follow-up. However, for most of the functional and psychological markers, no significant changes were found. CONCLUSIONS: A multi-modal rehabilitation programme for the chronic suffering attributed to WAD had positive effects according to several aspects of the retrospective evaluations, but according to most of the aspects evaluated prospectively the programme does not appear to have significant benefits.

Adult↗

Rock matrix diffusivity determinations by in-situ electrical conductivity measurements.

A fast method to determine rock matrix diffusion properties directly in the bedrock would be valuable in the investigation of a possible site for disposal of nuclear waste. An "effective diffusivity borehole log" would provide important information on the variability of this entity over the area studied. As opposed to traditional matrix diffusion laboratory experiments, electrical conductivity measurements are fast, inexpensive and also easy to carry out in-situ. In this study, electrical resistivity data from borehole logging, as well as from measurements on the actual core, is evaluated with the purpose of extracting matrix diffusivity data. The influence of migration of ions in the electrical double layer, which can be of great importance in low ionic strength pore water, is also considered in evaluating the in-situ data to accurately determine the effective pore diffusivity. The in-situ data compare fairly well to those measured in the rock core.

Diffusion↗

Substrate and product dependence of force and shortening in fast and slow smooth muscle.

To explore the molecular mechanisms responsible for the variation in smooth muscle contractile kinetics, the influence of MgATP, MgADP, and inorganic phosphate (P(i)) on force and shortening velocity in thiophosphorylated "fast" (taenia coli: maximal shortening velocity Vmax = 0.11 ML/s) and "slow" (aorta: Vmax = 0.015 ML/s) smooth muscle from the guinea pig were compared. P(i) inhibited active force with minor effects on the V(max). In the taenia coli, 20 mM P(i) inhibited force by 25%. In the aorta, the effect was markedly less (< 10%), suggesting differences between fast and slow smooth muscles in the binding of P(i) or in the relative population of P(i) binding states during cycling. Lowering of MgATP reduced force and V(max). The aorta was less sensitive to reduction in MgATP (Km for Vmax: 80 microM) than the taenia coli (Km for Vmax: 350 microM). Thus, velocity is controlled by steps preceding the ATP binding and cross-bridge dissociation, and a weaker binding of ATP is not responsible for the lower V(max) in the slow muscle. MgADP inhibited force and V(max). Saturating concentrations of ADP did not completely inhibit maximal shortening velocity. The effect of ADP on Vmax was observed at lower concentrations in the aorta compared with the taenia coli, suggesting that the ADP binding to phosphorylated and cycling cross-bridges is stronger in slow compared with fast smooth muscle.

Actins↗

Perinatal changes in expression of aquaporin-4 and other water and ion transporters in rat lung.

1. At birth, rapid removal of lung liquid from potential airspaces is required to establish pulmonary gas exchange. To investigate the role for water channels, aquaporins (AQP) and ion transporters in this process, the mRNA expression of AQP, Na+,K(+)-ATPase and the amiloride-sensitive Na+ channel (ENaC) were studied in the fetal and postnatal rat lung. 2. The mRNA expression of all transporters studied increased postnatally. 3. The following water channels were expressed in the lung, AQP1, 4 and 5. The most specific perinatal induction pattern was observed for AQP4. A sharp and transient increase of AQP4 mRNA occurred just after birth coinciding with the time course for clearance of lung liquid. This transient induction of AQP4 mRNA at birth was lung-tissue specific. Around birth there was a moderate increase in AQP1 mRNA, which was not transient. AQP5 increased continuously until adulthood. 4. Fetal lung AQP4 mRNA was induced by both beta-adrenergic agonists and glucocorticoid hormone, which are factors that have been suggested to accelerate the clearance of lung liquid. 5. Immunocytochemistry revealed that AQP4 was located in the basolateral membranes of bronchial epithelia in newborn rats, consistent with the view that this is the major site for perinatal lung liquid absorption. 6. The Na+,K(+)-ATPase alpha 1 subunit and ENaC alpha-subunit mRNA also increased around birth, suggesting that they co-operatively facilitate lung liquid clearance at birth. 7. These data indicate that removal of lung liquid at birth is associated with pronounced and well-synchronized changes in the expression of AQP and the ion transporters studied. The transient perinatal induction of AQP4, which could be prenatally induced by beta-adrenergic agonists, and the localization of this water channel strongly suggest that it plays a critical role for removal of lung liquid at the time of birth.

Adrenergic beta-Agonists↗

High progesterone is related to effective human labor. Study of serum progesterone and 5alpha-pregnane-3,20-dione in normal and abnormal deliveries.

BACKGROUND: The role of progesterone levels during human labor is unclear. OBJECTIVE: To investigate serum concentrations of progesterone and 5alpha-pregnane-3,20-dione in normal and abnormal deliveries. METHODS: Venous and umbilical cord serum samples were collected from 108 parturient women. In a further 49 deliveries, arterial and venous umbilical cord sera were collected separately. The concentrations of progesterone and 5alpha-pregnane-3,20-dione were determined by radioimmunoassay. The delivery modes studied were: elective cesarean section; oxytocin-resistant dystocia; normal but induced delivery, and normal spontaneous delivery. RESULTS: Progesterone concentrations in maternal and umbilical serum were higher following normal labor than after dystocia (p<0.005) and elective cesarean section (p<0.005). The maternal and umbilical progesterone concentrations in dystocia and elective cesarean section were between 77-43% of those in normal labor. The concentrations did not vary between gestational weeks 37 and 42, within the different modes of delivery. The 5alpha-pregnane-3,20-dione serum concentration in the fetal compartment was twice that in the maternal compartment (p<0.001); its concentration in venous umbilical serum was higher than in corresponding arterial samples (p<0.001). No distinct differences in the 5alpha-pregnane-3,20-dione serum concentration were found with regard to parity or mode of delivery. CONCLUSION: High progesterone concentrations during parturition appear to be related to effective labor. The findings support results from in vitro experiments on human term myometrium.

5-alpha-Dihydroprogesterone↗

Self-marking in written examination: a way of feedback and learning.

A new form of written examination, involving self- and teacher assessment, immediate feedback and discussion time with the course leader has been tried and evaluated at seven undergraduate courses in obstetrics and gynaecology at Umeå University, Sweden. Out of 112 students (59 women, 53 men), 101 (90%) rated this method as a better or far better learning situation than the traditional written examination. Twenty-seven (24%) students regarded the examination to be equal to, and 78 students (70%) thought it better or far better than, the conventional assessment as method to check the knowledge. According to the students, the method of self-marking increases the fairness of the examination and reduces the chances of cheating. No significant differences related to gender, age or test results were found. The examination time required of students was the same as with the traditional method, while the amount of time required of teachers was reduced.

Attitude↗

Continuous progesterone exposure associated with high contraction frequency in human term myometrial strips.

It has been shown that progesterone slightly reduced the work of human term myometrial strips. In vitro, 5 alpha-pregnane-3,20-dione and 3 alpha-hydroxy-5 alpha-pregnan-20-one, two major extra-hepatic metabolites of progesterone, had only minor effects or none at all. The myometrial strips were stored and superfused in a progestin-free buffer until the onset of contractions when progestin superfusion was commenced. In vivo, the human myometrium is never deprived of the influence of these steroids, either prior to or during labor. In the present investigation we studied whether progesterone and the two named progesterone metabolites would have a different effect when the myometrial strips were not deprived of steroid. Muscle biopsy samples from the lower uterine segment were immediately placed and stored in buffer containing progesterone, 5 alpha-pregnane-3,20-dione, or 3 alpha-hydroxy-5 alpha-pregnan-20-one. The strips were then bisected; one half was superfused with progestin buffer, and the other half with plain buffer to serve for control purposes. In strips continuously exposed to progesterone, the onset of contractions was delayed, compared with their progesterone-depleted controls. This was as expected, according to current opinion regarding progesterone and parturition. Once muscular contractions were established, the contraction frequency was significantly higher, due to a shorter muscular relaxation time, in the progesterone-superfused strips than in the controls and strips treated with progesterone metabolite superfusion. This was unexpected and can be interpreted as if continuous presence of progesterone facilitates human myometrial contraction frequency once contractions have started. Conversely, the 5 alpha-progesterone metabolites showed no effect or minor effects.

Adult↗

Testing of quantitative parameters in the 32P-postlabelling method.

The 32P-postlabelling technique involves many steps that need to be carefully controlled in order to obtain a reliable quantitative determination of DNA adducts. We have studied several of the parameters involved in the DNA digestion procedures as well as those concerned in the phosphorylation reaction. Since adducts behave in very different ways in the labelling reaction, an individual protocol has to be worked out for each particular type of adduct. Quantitation is usually possible only if a synthesized standard of the adduct under investigation is run in parallel to the DNA samples throughout the whole procedure.

Adenosine Triphosphate↗

Antitachyphylactic effects of progesterone and oxytocin on term human myometrial contractile activity in vitro.

OBJECTIVE: To determine whether progesterone causes any changes in the action of oxytocin on the contractile activity of term human myometrium in vitro. METHODS: Myometrial biopsies from 13 term pregnant women undergoing cesarean delivery were immediately immersed in Hepes buffer or buffer containing 5 micrograms/mL progesterone. In the laboratory under a stereomicroscope, the specimens were dissected into 1 x 7.5-mm muscle strips. These were mounted into six tissue baths and superfused with Hepes buffer and buffer containing 5 micrograms/mL progesterone, 5 micrograms/mL progesterone plus 10 microU/mL oxytocin, 5 micrograms/mL progesterone plus 100 microU/mL oxytocin, 10 microU/mL oxytocin, and 100 microU/mL oxytocin. Isometric tension was recorded constantly for at least 3 hours. RESULTS: The frequency of myometrial contractions and tonus increased by superfusion with progesterone, progesterone plus oxytocin, and oxytocin alone compared to buffer. In addition, a gradual decrease in frequency was observed after 60 minutes of contractions with oxytocin alone, whereas progesterone plus oxytocin had no such decrease. The activity area of contractions was greater with 10 microU/mL oxytocin and decreased with progesterone, progesterone plus both concentrations of oxytocin, and 100 microU/mL oxytocin alone, compared to buffer. CONCLUSIONS: Progesterone stimulated the frequency of contractions and tonus of strips from the lower uterine segment of term human myometrium. A lasting increase in the frequency of contractions was observed with superfusion of progesterone plus oxytocin, suggesting that progesterone counteracted the reaction of tachyphylaxis to oxytocin.

Dose-Response Relationship, Drug↗

Unexpected stimulatory effect of progesterone on human myometrial contractile activity in vitro.

OBJECTIVE: To investigate the effects of continuous exposure of progesterone on contractile activity of term human myometrium in vitro. METHODS: Myometrial biopsy specimens were obtained from 14 term pregnant women undergoing elective cesarean. The specimens were immediately immersed in Hepes buffer and buffer containing 0.33, 4.1, and 70 micrograms/mL progesterone. Muscle biopsies were dissected along the bundles of smooth muscle under stereomicroscope. These myometrial strips were mounted in tissue baths and superfused with Hepes buffer and buffer containing different concentrations of progesterone. RESULTS: The progesterone concentration of 0.33 microgram/mL had no significant effect on myometrial contractile activity. The concentrations of 4.1 and 70 micrograms/mL increased the frequency of contractions (P < .01 for each) and tonus (P < .01 for each), decreased the activity area of contractions (P < .01 for each), and delayed the onset of contractions (P < .01 and P < .05, respectively). CONCLUSION: When the myometrium is not deprived of progesterone, this hormone may have excitatory effects on the frequency of contractions and tonus of the lower uterine segment of term human myometrium.

Adult↗

Some quantitative considerations about DNA adduct enrichment procedures for 32P-postlabelling.

The concentrations of 2'-deoxyribonucleoside-3'-monophosphates remaining in calf-thymus DNA digests after nuclease P1 digestion or extraction into 1-butanol, the most commonly used adduct enrichment procedures prior to the application of the 32P-postlabelling assay, were measured using HPLC and 32P-postlabelling methods. When 10 micrograms of DNA digested to mononucleotides was used, the total amount of nucleotides remaining in the samples were approximately 4 and approximately 14 pmol after nuclease P1 treatment or 1-butanol extraction respectively. The influence of various concentrations of normal nucleotides on the labelling efficiency of a 2'-deoxyguanosine-3'-monophosphate adduct of benzo[a]pyrene diol-epoxide was also studied and found to depend upon the ratio of normal nucleotides/adducted nucleotides present in the sample. Also, the ATP/normal nucleotides ratio in the phosphorylation reaction may affect the quantitation of the adducts and thus deserves due consideration.

1-Butanol↗

Effects in vitro of progesterone and two 5 alpha-reduced progestins, 5 alpha-pregnane-3,20-dione and 5 alpha-pregnane-3 alpha-ol-20-one, on contracting human myometrium at term.

Progesterone is known to prevent labour at term in domestic animals, but its effect in primates is uncertain. 5 alpha-reduced progesterone metabolites are more potent central nervous system depressants than progesterone is itself. Progesterone and its 5 alpha-reduced metabolites also relax pregnant rat myometrium in vitro. The serum concentration of the initial 5 alpha-reduced metabolite, 5 alpha-pregnane-3,20-dione, is high during pregnancy, but decreases significantly prior to parturition. The next metabolite, 5 alpha-pregnane-3 alpha-ol-20-one, has anaesthetic properties in human beings. The purpose of this study was to ascertain whether these progesterone metabolites also suppress contracting human uterine muscle at term. An in vitro model was devised. Strips of human myometrial muscle were mounted in organ chambers and after regular contractions had become established, the strips were superfused with progestin solutions. The progestins were dissolved in the buffer using an ultrasound bath. Progesterone, used as reference substance, slightly reduced the measured amount of muscular work performed per contraction, recordable after 18 min of exposure (p less than 0.05). Similar results have been reported previously in the literature; 5 alpha-pregnane-3 alpha-ol-20-one showed the same tendency though not significant at the 5% level. 5 alpha-pregnane-3,20-dione evidently reduced the contraction frequency after 10 min of exposure (p less than 0.05). None of the substances affected the duration of the contraction. These 5 alpha-reduced progesterone metabolites are thus not potent inhibitors of contracting human term myometrium in vitro.

5-alpha-Dihydroprogesterone↗