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Biomedical subjects

B Gustafsson

Publications and source records attributed to B Gustafsson.

At least 199 records · Page 11Linked to original sources

Improved in vitro bioassay of follitropin.

The FSH-dependent aromatase activity of Sertoli cell enriched cultures of testicular cells from immature rats was utilized as a sensitive and specific in vitro bioassay for FSH activity. The conversion of 19-hydroxyandrostenedione to estradiol was used as the end point of the assay. By the introduction of a phosphodiesterase inhibitor into the culture medium, the sensitivity was improved 5-10 times, so that 0.05 mIU of FSH showed a response significantly different from the blank. Other pituitary or placental hormones, such as hLH, hTSH and hCG exhibited less than 0.8% cross-reactivity, whereas hGH, hPRL, ACTH1-24, LH-RH, and prostaglandin E2 alpha did not show any cross-reaction at the doses tested.

Animals↗

Increased excitability of hippocampal unmyelinated fibres following conditioning stimulation.

Unmyelinated fibres in the stratum radiatum (area CA1) were electrically stimulated in hippocampal slices from guinea pigs. The size of the evoked fibre volley was increased by a preceding conditioning stimulation to the same fibres, provided that the strength of the conditioning stimulus was larger than that of the test pulse. This facilitation was maximal for 20-30 ms interstimulus intervals and had a duration of about 200 ms. The results are compatible with an increased excitability (reduction in threshold) specific for fibres activated by the conditioning stimulation.

Animals↗

Shape of frequency-current curves in CAI pyramidal cells in the hippocampus.

Frequency-current curves for CA1 hippocampal pyramidal neurons are shown to have basically the same shape as those for spinal motoneurones, with a region of shallow slope at low frequencies, preceding a sleep linear or upward convex region at higher frequencies. The frequency range is, however, displaced towards lower frequencies. The results suggest, in a qualitative sense, that the firing behaviour of CA1 pyramidal cells is regulated by the afterhyperpolarization, at least in the low frequency range.

Animals↗

Excretion of paracetamol in human breast milk.

Breast milk and plasma levels of paracetamol were monitored in 3 lactating women after ingestion of a single 500 mg dose of paracetamol. The paracetamol concentrations were consistently lower in milk, with a mean milk/plasma AUC ratio of 0.76. This value was in close agreement with the milk/plasma partition ratio of 0.81 found in vitro, and could be related to quantitative binding differences between the two fluids. The half-lives of paracetamol in plasma and breast milk were almost identical, with an overall mean of 2.7 h. As less than 0.1% of the maternal dose would be present in 100 ml milk, breast feeding need not be discontinued due to paracetamol treatment in conventional dosage.

Acetaminophen↗

Two types of synaptic facilitation recorded in pyramidal cells of in vitro hippocampal slices from guinea pigs.

PyramidaL cells in CA1 hippocampus show two types of increase in the excitatory postsynaptic potential (EPSP) during paired pulse stimulation of the afferent fibres in stratum radiatum. For 15-300 ms interstimulus intervals, both the initial slope and the peak amplitude of the EPSP are increased, which is mainly due to an increased excitatory synaptic current. For 300 ms-2 s intervals, the predominant change is an increase in the peak amplitude. The latter type of facilitation is caused by a decrease in a superimposed inhibitory postsynaptic potential (IPSP).

Animals↗

Maternal and foetal drug levels after epicutaneous application of a local anaesthetic formulation containing ketocaine for possible use as pain relief in labour.

A local anaesthetic formulation (A 2358) containing ketocaine, a local anaesthetic drug, was applied epicutaneously to the low back. Two compresses soaked with A 2358 were applied for 1 hour in 26 normal labours for relieving referred pain from the low back. The maternal blood ketocaine levels remained low, compared to higher systemic levels reported in other studies. Maternal heart rate and blood pressure were stable during the application time. The mean umbilical vein/maternal vein and umbilical artery/maternal vein concentration ratios were 0.20 +/- 0.10 and 0.21 +/- 0.09. In addition, the foetal heart rate findings and the conditions of the neonates were satisfactory, thus suggesting the foetal safety of this analgesic method.

Adolescent↗

A new beta 2-adrenoceptor agonist with alpha 1-adrenoceptor blocking properties.

The phenylethanolamine D2343 exhibits a dualistic adrenoceptormediated effect, i.e, a beta-agonistic effect combined with an alpha-antagonistic one. Tracheal smooth muscles and heart preparations were used to gauge the agonistic effect of adrenergic beta-receptors. Rabbit aorta and rat vas deferens were used to determine the alpha-adrenoceptor blocking activity. The beta-adrenoceptor activity of D2343 was classified as beta 2-type with about the same efficacy as the beta 2-selective terbutaline on tracheal muscle. The effect on isolated heart preparations was greater than that produced by terbutaline. The alpha-receptor blocking capacity was directed against the alpha 1-receptor type and was of nearly the same potency as for phentolamine.

Adrenergic alpha-Antagonists↗

Relief from pain localized to the lower back in early labour. A double blind trial of ketocaine, a new, highly effective, local, cutaneous analgesic (A 2358, Ane-Pad), and placebo.

Pain localized to the lower back in the first stage of labour in 47 primiparous women was treated by epicutaneous application of ketocaine or placebo compresses. Twenty-three patients were treated with ketocaine compresses (Ane-Ped), and 24 patients with compresses soaked with isotonic saline. The pain relieving effect was almost the same in both treatment groups. Pain localized to the lower back was reduced in about 50% of the patients after one hour's application of ketocaine or placebo compresses. Supplementary analgesics had to be administered in about 60% of the patients in each group. No maternal or foetal systemic side effects related to the treatment were registered. Local erythema on the application area was only reported in the ketocaine group. The frequency of feeling of warmth during the application of compresses of ketocaine were high compared to the placebo group, 78% and 29% respectively.

Adult↗

Effect of membrane polarization and synaptic activity on the timing of antidromic invasion.

The latency from the stimulus (S) to the IS and SD components of the antidromic spike was measured in motoneurones and spinocerebellar tract cells following displacement of the membrane potential either by current pulses or by synaptic potentials. Changes in the latency to the SD spike (S-SD delay) were mainly caused by changes in the IS-SD delay and varied from 10 to 100 musec per mV change in membrane potential, depending on the initial value of the IS-SD delay. Changes in the S-IS delay were also observed and these changes could, especially in spinocerebellar cells, give a significant contribution to the change in the total delay. EPSPs shortened the S-SD delay as efficiently as current-evoked depolarizations of similar magnitude while IPSPs were often more effective in prolonging the delay than current-evoked hyperpolarizations. This difference was related to the larger conductance increase during IPSPs than during IPSPs and to the longer IS-SD delays at hyperpolarized potentials. The presented data contribute to the understanding of the method which uses extracellular recording of antidromic latency changes as an indirect measure of intracellular membrane potential changes. Our results show that the recording of antidromic latency changes is a particularly sensitive method for detecting inhibition of neurones.

Animals↗

Cytofluorometric analysis of anaphylactic secretion of 5-hydroxytryptamine and heparin from rat mast cells.

Actively sensitized rat mast cells were stimulated to secretion in vitro by means of an anaphylactic IgE antigen reaction or with polymyxin B. Release of 5-hydroxytryptamine (5-HT) and heparin from the cells and from individual granules, extruded or displaced from stimulated cells with micromanipulation, was quantitated cytofluorometrically. Several similarities in action between the two secretagogues were found. All extruded and some intracellular granules from stimulated cells lacked 5-HT, and no heparin was released from the granules. Heparin secretion from mast cells was due to granule extrusion alone. Further, the proportions between 5-HT and heparin released from mast cells indicated that amine release, too, is mainly, but not exclusively, associated with overt granule exocytosis. The results suggested that the first extruded granules are the richest in both 5-HT and heparin. Antigen-induced secretion was not as vigorous as that induced by polymyxin and, unlike the latter, followed after a short lag of about 20 sec.

Anaphylaxis↗

Lipopolysaccharide and lipid A-induced human blood lymphocyte activation as detected by a protein A plaque assay.

Various purified cell wall lipopolysaccharides (LPS) from gram-negative bacteria and derivatives of these LPS were tested for their stimulatory capacity for human peripheral blood cells. Immunoglobulin (Ig) production was tested by an indirect plaque-forming cell assay using Staphylococcus aureus protein A-coupled erythrocytes and specific anti-Ig as developing serum. This method allows the detection of the majority of cells secreting Ig of a single class, and the number of plaque-forming cells detected are approximately 100-1000 times the amount obtained using normal sheep red cells as targets. LPS containing the O antigen-specific chain, as well as mutant products only containing lipid A and ketodeoxyoctonate trisaccharide, could induce cell division and antibody synthesis. The polypeptide antibiotic polymyxin B was found to inhibit LPS-induced activation. Furthermore, purified lipid A, complexed with bovine serum albumin, was also found to activate human peripheral blood B cells. These findings demonstrate that human peripheral blood lymphocytes can be activated by LPS and also indicate that lipid A is the active part of these molecules.

DNA↗

A model for evaluating the analgesic effect of a new fixed ratio combination analgesic in patients undergoing oral surgery.

A special model designed for evaluating the analgesic effect of oral analgesics was based on a short-time registration period of immediate postoperative pain. One-hour intervals in pain registration and a minimum of 2 h between the tablet intake allowed a good estimation of changes in pain levels. The patient material consisted of 112 patients and from each patient a lower impacted wisdom tooth was removed. The test model was used to compare two analgesic drugs with placebo. The two pharmacologically active preparations were Doleron (dextropropoxyphene, acetylsalicylic acid, phenazone, caffeine and Transergan) and Astra 2167 (dextropropoxyphene and acetylsalicylic acid). The trial was double blind and the tablets were administered according to a crossover design. There was no statistically significant difference in analgesic effect between Astra 2167 and Doleron, and both drugs were superior to placebo. Finally, the trial showed that a reduction of the number of components of a compound analgesic to some degree reduced the pain relieving effect on this particular postoperative pain. This observed reduction was however, not statistically significant.

Adult↗

Changes in motoneurone electrical properties following axotomy.

1. Passive electrical properties, afterpotential properties and the pattern of repetitive discharge induced by constant current injection were studied in axotomized lumbar motoneurones. 2. Following axotomy, the motoneurones showed a larger input resistance and membrane time constant, but had a normal electrotonic length. 3. Duration and peak amplitude of the afterhyperpolarization (ahp) were on average unchanged following axotomy. There was, however, a significant reduction in the conductance underlying the ahp. The distribution of values for ahp duration was also narrower following axotomy, with an absence of long and short values. 4. As in normal motoneurones, the ahp conductance, calculated from the voltage, decayed in an approximately exponential manner with a phase of slower decay corresponding to the hyperpolarizing phase of the ahp. The phase of slower decay was, however, less accentuated and several axotomized motoneurones showed an exponential decay of the ahp conductance. 5. The frequency--current (f--I) curves for the first interspike intervals were, as in normal motoneurones, non-linear, deviating upwards at higher frequencies. The steady-state f--I relations were, however, linear in most of the axotomized neurones. The slopes of the f--I curves were steeper following axotomy. These steeper slopes were well correlated with the decreased ahp conductance. 6. The interspike voltage trajectories were similar to those in normal motoneurones, i.e. concave at low current strength and changing to a convex shape with increasing current injection. The changes in the trajectory shape were not correlated with the changes in the slope of the f--I curves. 7. It is concluded that the afterhyperpolarization conductance is the major factor in the regulation of repetitive firing in axotomized motoneurones.

Action Potentials↗