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Biomedical subjects

B Gustafsson

Publications and source records attributed to B Gustafsson.

At least 217 records · Page 12Linked to original sources

Saturating summation of the afterhyperpolarization conductance in spinal motoneurones: a mechanism for 'secondary range' repetitive firing.

Summation of the potassium conductance (GK) changes underlying the spike afterhyperpolarization (AHP) has been studied in cat spinal motoneurones. Cells were directly activated by one to five short current pulses at constant rate, each evoking an action potential. The analysis was restricted to cells displaying an approximately exponential decay of the AHP conductance. In these neurones the AHP conductances given by successive spikes were found to summate in a non-linear manner. This nonlinear summation seemed well described by a neurone model based on modified Hodgkin-Huxley equations. From the model equations the total AHP conductance in motoneurones could be calculated from values of GK measured experimentally at different times during the summation process. Adaptation and steady-state firing in motoneurones are assumed to be governed by summation of AHP conductance. The same model was then utilized for simulating neuronal repetitive firing in response to current steps. Such simulations were performed after substitution of the model parameters with values measured in individual motoneurones which had also been fired repetitively by intracellular injection of long-lasting current steps. The amount of adaptation and the shape and slopes of the steady-state frequency-to-current relation were found to coincide in the model and in the corresponding motoneurones.

Action Potentials↗

Absorption and elimination of D-propoxyphene, acetyl salicylic acid, and phenazone in a combination tablet (Doleron): comparison between young and elderly subjects.

The single-dose kinetics of D-propoxyphene, acetyl salicylic acid and phenazone, given in a combination tablet (Doleron), were compared in young and elderly subjects. Serial blood samples were taken 0--48 hours after administration. The plasma concentrations of propoxyphene and of its major metabolite, norporpoxyphene, were assessed by mass fragmentography, those of phenazone by gas chromatography, and those of acetyl salicylic acid plus salicylic acid by spectrofluorometry. Neither for propoxyphene, norpropoxyphene, acetyl salicylic acid nor phenazone did the areas under the concentration curves or the elimination half-lives differ between young and elderly subjects. These data do not provide pharmacokinetic support for a general reduction of the Doleron dosage in elderly subjects.

Administration, Oral↗

Afterhyperpolarization mechanism in the dorsal spinocerebellar tract cells of the cat.

1. The longlasting afterhyperpolarization (a.h.p.) following single or short trains of spikes in dorsal spinocerebellar tract (DSCT) neurons of the cat has been studied with intracellular recording techniques. 2. The a.h.p. amplitude was found to be potential dependent, increasing with depolarization and decreasing with hyperpolarization of the membrane. With large membrane hyperpolarization, the a.h.p. could be reversed in direction, the estimated reversal level being around 30 mV more negative than the threshold potential for spike initiation. The a.h.p. amplitude was also little affected by Cl- ions injected into the cell. 3. The a.h.p. was associated with an increase in the membrane conductance, as measured with short current pulses. The major part of the conductance change was related to the a.h.p. itself and not secondary to the hyperpolarization, i.e. to an anomalous rectification. A conductance change was also found when the membrane potential was polarized close to the a.h.p. reversal level. There was a clear correlation between the a.h.p. amplitude and the measured conductance changes. 4. It is concluded that the a.h.p. in DSCT neurones, as in spinal motoneurones, is caused primarily by an increase in membrane conductance to potassium ions. 5. The time course of the conductance change underlying the a.h.p. was calculated from the a.h.p. voltage and a mathematical expression describing this time course is given. The properties of the a.h.p. in DSCT cells are compared with those in spinal motoneurones and the functional significance of the differences is discussed briefly.

Action Potentials↗

Effect of repetitive activation on the afterhyperpolarization in dorsal spinocerebellar tract neurones.

1. The changes in the afterhyperpolarization (a.h.p.) with repetitive activation have been studied in dorsal spinocerebellar tract cells of the cat using intracellular recording techniques. 2. The a.h.p. following a single spike was conditioned at different interspike intervals by a single preceding spike. In the majority of neurones the a.h.p. following a spike added approximately linearly with that generated by a preceding spike. 3. In other cells the a.h.p. following a spike was instead depressed by a preceding spike. THis depression was approximately constant at interspike intervals less than the a.h.p. duration (50-100 msec). Thereafter the a.h.p. slowly recovered during the next 100-300 msec. There was no associated decrease in the initial brief hyperpolarizing undershoot. 4. With shortlasting repetitive activation at high frequency (greater than 100 impulses/sec) the a.h.p, peak amplitude increased progressively with successive spikes (5-15 spikes). No change in the time constant of decay was observed. A good correspondence was found between the observed increase in peak amplitude of the a.h.p.s and that given by a theoretical linear superposition of the successive a.h.p.s. 5. Changes in the brief hyperpolarizing undershoot with repetitive activation is also described.

Action Potentials↗

Firing behaviour of dorsal spinocerebellar tract neurones.

1. The repetitive discharge evoked by constant current injection from an intracellular micropipette has been studied in dorsal spinocerebellar tract cells of the cat. 2. The discharge frequency decreased with time, the decrease being more pronounced at high current intensities. Most of the frequency change occurred during the first ten intervals but the decrease continued slowly for several seconds. In some cells the frequency rose initially, the first interspike interval being larger than immediately succeeding ones. 3. The frequency-current (f/I) curves for the first interspike intervals were S-shaped, as found in spinal motoneurones. With successive intervals the lower leg of the f/I curve extended to higher frequencies, giving a progressive linearization of the f/I curves. In almost all cells this linearization was completed at 200 msec after current onset. 4. The experimental f/I curves were compared with the f/I curves obtained with a simple neurone model based on the properties of the postspike afterhyperpolarization. For the first interspike interval there was a good agreement between the experimental and calculated f/I curves of individual neurones up to frequencies of several hundred impulses per second. In the high frequency range, it was necessary to compensate for changes in initial postspike voltage trajectories caused by the injected current. Other aspects of the firing of real neurones, such as the progressive linearization of the f/I curves, the negative adaptation and the changes in the interspike voltage trajectories with increasing current were also reproduced by the neurone model. 5. It is concluded that the conductance process underlying the postspike afterhyperpolarization is a major factor in the regulation of repetitive firing in dorsal spinocerebellar tract neurones.

Action Potentials↗

Cytofluorometric quantitation of 5-hydroxytryptamine and heparin in individual mast cell granules.

Cytofluorometric quantitation of 5-hydroxytryptamine (5-HT) and heparin in individual mast cell granules is described. The technique is based on micromanipulation of intact mast cells reacted with formaldehyde or stained with Berberine sulfate and the use of a cytofluorometer equipped with a sensitive peak detecting device. The quantities of 5-HT and heparin contained in mast cell granules which are of the order of 10(-16) and 10(-13) g, respectively were expressed as relative fluorescence guanta. The results of measurements on representative samples of mast cell granules indicate that all granules contain heparin as well as 5-HT, and that there are large variations in both 5-HT and heparin content within the granule populations of individual cells. A dose dependent increase in 5-HT content in both cells and individual mast cell granules occurred 24 hr after the injection of 10--50 mg L-5-hydroxytryptophan/kg intraperitoneally. There was no evidence for an increase in the heparin content of granules or cells, indicating that a new synthesis of granular macromolecules is not required for the 5-HT uptake. The results further suggest that 5-HT may be stored initially in a cytoplasmic extragranular pool and then taken up in the mast cell granules.

5-Hydroxytryptophan↗

Uptake of 5-hydroxytryptamine by mast cells in vivo: a cytofluorometric study of mast cells and individual mast cell granules.

Uptake, distribution and turnover of 5-Hydroxytryptamine (5-HT) was studied by cytofluorometric analysis of whole mast cells and individual granules. Injection of 5-HT as well as 5-Hydroxytryptophan (5-HTP) intraperitoneally or subcutaneously resulted in a parallel uptake of 5-HT in cells and granules. Intraperitoneal injections of 5-HT in such small quantities that may be available under physiological conditions resulted in an increase in fluorescence intensity of the mast cells, indicating a very efficient uptake mechanism for 5-HT in vivo. Much larger doses of 5-HTP were required to obtain a corresponding uptake of 5-HT in the mast cells. The 5-HT was rather rapidly taken up in the granules and eliminated very slowly, at the same rate both from granules and mast cells. The low elimination rate confirms our previous findings that the turnover of 5-HT is much lower in mast cells than in other amine containing cell systems. The combination of an extremely efficient, rapid uptake of 5-HT with a slow elimination suggests a specific function for mast cells in the regulation of free amine concentrations in tissues.

5-Hydroxytryptophan↗

Bioavailability of D-propoxyphene, acetyl salicylic acid, and phenazone in a combination tablet (Doleron): interindividual variation and influence of food intake.

The influence of food intake on the bioavailability of three analgesic compounds--propoxyphene chloride, acetyl salicylic acid and phenazone--in a combination tablet, Doleron, has been examined in eight healthy volunteers. A single oral dose was given both on an empty stomach and together with a standardized breakfast meal. The plasma concentrations of propoxyphene, its major metabolite norpropoxyphene, salicylic acid and phenazone were determined by mass fragmentography, spectrofluorimetry and gas chromatography. Concomitant food intake had no consistent influence on the bioavailability of any of the components. Hence, doleron may be taken together with meals as well as between meals. Large interindividual variations in propoxyphene and phenazone concentrations were found, indicating that an optimal effect will not always be obtained by standard doses.

Adult↗

Respiratory distress syndrome and thrombotic, non-bacterial endocarditis after amitriptyline overdose.

Three patients with documented or suspected amitriptyline poisoning developed a uniform clinical picture with progressive respiratory insufficiency, thrombocytopenia and evidence of embolization. Post-mortem examination revealed equally uniform changes: thrombotic, non-bacterial endocarditis (TNBE) with multiple embolization and marked pulmonary stiffness with extensive invasion of alveoli with connective tissue. The lung pathology and clinical picture of progressive respiratory insufficiency are in agreement with the respiratory distress syndrome (RDS) in the adult. The simultaneous occurrence of RDS and TNBE suggests a similar pathogenesis. Prophylactic measures are described.

Adolescent↗

Cytofluorometric quantitation of 5-hydroxytryptamine in mast cells: an improved technique for the formaldehyde condensation reaction.

A simple technique for the condensation of cellular 5-hydroxytryptamine (5-HT) with formaldehyde gas is described. The technique, which is especially suited for quantitative cytofluormetric studies, involves the generation of formaldehyde gas from dry paraformaldehyde in a closed reaction vessel with the addition of a measured quantity of water. The fluorescence yield of 5-HT was tested at various humidities. Optimal results were obtained with the addition of 100 mg water to a 1000 ml reaction vessel containing 6 g of dry paraformaldehyde. A major advantage of the method if the fact that the humidity during the reaction can be precisely controlled. The fluorescence yield of 5-HT, tested over a 50 day period showed excellent reproducibility. The stoichiometry of the reaction was tested by comparison of cytofluormetic data with that obtained by analysing the 5-HT content of pooled mast cells with an independent biochemical method. A highly satisfactory correlation (r = 0.96) was obtained within the range of 0.1 to 4 pg of 5-HT per cell. The limit of sensitivity of the cytofluorometric method was found to be of the order of 10(-13) g, and was determined by the fluorescence blank of the mast cells. This contributes to between 10 and 30 per cent of the total fluorescence emission from mast cells containing about 0.2 pg of 5-HT.

Animals↗

Alkaline phosphatase activity of epididymal contents in boars with normal or reduced spermatogenesis.

The alkaline phosphatase activity was measured in testicular fluid and in epididymal plasma from caput and cauda epididymidis in boars with normal sperm production and in boars in which the number of spermatozoa passing from the testis to the epididymidis was reduced. The testicular fluid and the epididymal plasma from caput epididymidis contained low amounts of alkaline phosphatase in comparison with epididymal plasma from the cauda. This applies to both groups of boars e.g. boars with normal as well as with totally lacking or lowered sperm production. As no fluid resorption takes place between caput and cauda the distal part of the epididymidis must be the main production site for alkaline phosphatase. The production there is not related to the presence of spermatozoa in the duct. In the caput, on the other hand, it seems that the level of alkaline phosphatase in some way is influenced by the sperm supply to the duct.

Alkaline Phosphatase↗

Direct and indirect activation of nerve cells by electrical pulses applied extracellularly.

1. The mode of activation of nerve cells by extracellular stimuli was investigated while recording from a selected cell with one electrode, and applying current pulses around this cell with another electrode. The analysis was done on motoneurones and on spinal border cells from lower lumbar segments in the cat. 2. Directly evoked action potentials were defined by their appearance in an all-or-none fashion with stable latencies of less than 0-5 ms. The lowest thresholds for their generation were 0-15-0-20 muA in the spinal border cells and 0-35-0-40 muA in the motoneurones. In the main series on motoneurones a correlation has been established between different positions of the extracellular stimulating electrode in relation to the cells and the thresholds for the direct excitation of these cells. The position of the electrode were defined on the basis of an analysis of the IS and SD components of the action potentials recorded extracellularly around the cell when evoked by current pulses applied through the intracellular electrode; both the amplitudes of these IS and SD components and their timing with the IS and SD spikes, which were simultaneously recorded with the intracellular electrode, were then taken into account. The lowest thresholds (less than 2 muA) for the direct activation of cells were found nearest the initial segment of the axon. Their values increased to about 5 mu A at near-soma positions and to greater than 10 muA at near-dendrites positions about 150 mum away. 3. Transsynaptically evoked action potentials which were clearly set up by the preceding e.p.s.p.s appeared with latencies greater than 0-7 ms. When single current pulses were used, the lowest thresholds for transsynaptic spike activation were usually greater than 5-10 muA but they considerably decreased with repetitive stimuli. These thresholds were higher than the thresholds for the direct activation of cells within the region of the initial segment, of the same order of magnitude near the soma, and lower when the stimulating electrode was nearer the dendrites than the soma and generally at all larger distances from the cells. 4. All the observations on direct excitation of cells by extracellular stimuli (generation of the IS spike before the SD spike, lowest thresholds near the region of the initial segment of the axon, similar rates of increase in these thresholds with distance as for fibres) lead to the conclusion that the effects of the extracellular stimuli are exerted primarily via spread of current to the initial segment of the axon and its depolarization. 5. Late extracellular negativities presumably related to dendritic activation were observed in a few cells. These negativities were synchronous with late components of the intracellulary recorded action potentials.

Action Potentials↗

Sequential changes of estrogens and progesterone at prostaglandin-induced parturition in the sow.

Parenteral administration of prostaglandin F2alpha (PGF2alpha) is efficient in inducing parturition in late pregnant swine. The purpose in the present study was to investigate the sequential changes of progesterone and estrogens at prostaglandin-induced parturition in the sow. Six of 7 sows (86%) treated once intramuscularly with 12.5 mg of PGF2alpha on days 110, 111, 112, or 113 of pregnancy farrowed within 39 hours after the injection. One PGF2alpha-treated sow and 2 sows given placebo injections on days 110 and 111 of pregnancy farrowed 90 to 130 hours later. The injection of PGF2alpha decreased the peripheral plasma concentration of progesterone in a manner similar to that observed immediately prepartum in normally farrowing sows. Estrogen patterns were similar in PGF2alpha-treated and control sows.

Animals↗

Acute poisoning with dextropropoxyphene. Clinical symptoms and plasma concentrations.

Out of 14 cases of poisoning assumed to be due to dextropropoxyphene-containing drugs, propoxyphene and its main metabolite norpropoxyphene could be demonstrated in 11. The concentrations of the drugs were determined shortly after admission and then after 2, 4, 6 and 10 hours (in four cases also after 16 hours). The highest plasma concentration of propoxyphene, 0.74 mug/ml, was found in one case of fatal poisoning. Another patient with a plasma concentration of 0.51 mug/ml showed signs of severe respiratory depression but survived after respirator therapy. In the patients with lower plasma concentrations the poisoning had a benign course. In most cases the plasma concentration of norpropoxyphene exceeded that of propoxyphene even in the first blood sample.

Acidosis↗

Morphological effects of rapeseed oil in rats. III. Studies in germ-free rats.

The morphological effects on the myocardium of feeding rapeseed oil were compared in conventional and germ-free rats in short-term experiments (10 days). It was concluded that the fatty accumulation in the heart muscle cells occurring in rats fed rapeseed oil was not influenced by the presence or absence of a normal intestinal flora. In long-term experiments (80 days) under similar conditions, the myocardial effects of feeding germ-free rats with conventional rapeseed oil, rapeseed oil from the Canadian cultivar Oro very low in erucic acid, or arachis oil were studied in serial sections. Severe myocardial lesions developed in the group of rats fed conventional rapeseed oil, while in the other two groups the myocardium was completely normal. These results give no support to the theory that other factors than C22:1 acids in rapeseed oil are responsible for the myocardial lesions.

Animals↗