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G Wahlström

Publications and source records attributed to G Wahlström.

At least 19 recordsLinked to original sources
PubMed2004

Dynamic aspects of acute tolerance to allopregnanolone evaluated using anaesthesia threshold in male rats.

BACKGROUND: It is unclear if allopregnanolone (AlloP) anaesthesia can induce tolerance. Acute tolerance is defined as altered sensitivity to a drug during a single continuous exposure. METHODS: Induction of acute tolerance to AlloP was studied in male rats using a threshold technique of deep anaesthesia. AlloP was infused at a dose rate of 4.0 mg kg(-1) min(-1). The infusion was stopped when a burst suppression of 1 s or more (the "silent second", SS) occurred in the EEG. To maintain anaesthesia, the infusion was restarted when no SS had been seen in the EEG for 1 min. This interrupted targeted infusion towards an EEG end-point (SS) was continued until 30, 60 or 90 min of anaesthesia had been reached. At these times the rats were killed and AlloP concentrations in serum, muscle, fat and different brain regions were determined by radioimmunoassay. RESULTS: Maintenance dose rate (MDR) was calculated using 20-min intervals. During anaesthesia the MDR increased (P<0.001) from 0.67 (sem 0.03) mg kg(-1) min(-1) (in the interval 10-30 min) to 0.98 (0.04) mg kg(-1) min(-1) (in the interval 65-85 min). After 60 min a slight increase in MDR was observed. After 90 min of anaesthesia the AlloP concentrations in the hippocampus and brainstem had increased by more than 50% compared with control values of 25.2 (1.13) and 52.7 (5.81) nmol g(-1) respectively, and after 60 min to around 40%. At 30 min no increase was seen in any brain region analysed. CONCLUSIONS: Measurements in vivo and in vitro record acute tolerance to AlloP occurring with a delay.

Adipose Tissue↗
PubMed2003

Phytoplankton successions under ice cover in four lakes located in north-eastern Sweden: effects of liming.

Phytoplankton successions under ice cover (January-March) were determined in four oligotrophic lakes (Burtjärn, Aspen, Vialamptjärn and Storkorstjärn) located in North-Eastern Sweden. The total phosphorus concentration in the lakes was less than 10 micrograms/L. Lake Burtjärn (reference lake) had a similar hydrology as Lake Aspen. Storkorstjärn and Vialamptjärn were of similar hydrology and had heavily colored water (> 100 mgpt/L). Aspen as well as vialamptjärn became continuously limed with calcium carbonate annually during the last decades. Biodiversity was considerably higher in the limed lakes (Aspen and Vialamptjärn) than in the untreated lakes (Burtjärn and Storkorstjärn). In Lake Burtjärn the most frequent species were Rhodomonas lacustris, Tabellaria flocculosa and Botryococcus braunii. Cryptophyceae (R. lacustris and Cryptomonas marssonii) and Dinophyceae (especially Gymnodinium lantzschii) were common phytoplankton groups in Lake Aspen. Tabellaria flocculosa was also the most common organism in both humic lakes Storkorstjärn and Vialamptjärn, other phytoplankton groups were in the humic lakes scarce. Liming was found to have profound effects on phytoplankton communities studied.

Acid Rain↗
PubMed2001

Twinfilin is required for actin-dependent developmental processes in Drosophila.

The actin cytoskeleton is essential for cellular remodeling and many developmental and morphological processes. Twinfilin is a ubiquitous actin monomer-binding protein whose biological function has remained unclear. We discovered and cloned the Drosophila twinfilin homologue, and show that this protein is ubiquitously expressed in different tissues and developmental stages. A mutation in the twf gene leads to a number of developmental defects, including aberrant bristle morphology. This results from uncontrolled polymerization of actin filaments and misorientation of actin bundles in developing bristles. In wild-type bristles, twinfilin localizes diffusively to cytoplasm and to the ends of actin bundles, and may therefore be involved in localization of actin monomers in cells. We also show that twinfilin and the ADF/cofilin encoding gene twinstar interact genetically in bristle morphogenesis. These results demonstrate that the accurate regulation of size and dynamics of the actin monomer pool by twinfilin is essential for a number of actin-dependent developmental processes in multicellular eukaryotes.

Actin Cytoskeleton↗
PubMed2001

Neuroactive steroids and central nervous system disorders.

Steroid hormones are vital for the cell life and affect a number of neuroendocrine and behavioral functions. In contrast to their endocrine actions, certain steroids have been shown to rapidly alter brain excitability and to produce behavioral effects within seconds to minutes. In this article we direct attention to this issue of neuroactive steroids by outlining several aspects of current interest in the field of steroid research. Recent advances in the neurobiology of neuroactive are described along with the impact of advances on drug design for central nervous system (CNS) disorders provoked by neuroactive steriods. The theme was selected in association with the clinical aspects and therapeutical potentials of the neuroactive steroids in CNS disorders. A wide range of topics relating to the neuroactive steroids are outlined, including steroid concentrations in the brain, premenstrual syndrome, estrogen and Alzheimer's disease, side effects of oral contraceptives, mental disorder in menopause, hormone replacement therapy, Catamenial epilepsy, and neuractive steroids in epilepsy treatment.

Alzheimer Disease↗
PubMed2001

The Drosophila VEGF receptor homolog is expressed in hemocytes.

Several signalling pathways have been defined by studies of genes originally characterised in Drosophila. However, some mammalian signalling systems have so far escaped discovery in the fly. Here, we describe the identification and characterisation of fly homologs for the mammalian vascular endothelial growth factor/platelet derived growth factor (VEGF/PDGF) and the VEGF receptor. The Drosophila factor (DmVEGF-1) gene has two splice variants and is expressed during all stages, the signal distribution during embryogenesis being ubiquitous. The receptor (DmVEGFR) gene has several splice variants; the variations affecting only the extracellular domain. The most prominent form is expressed in cells of the embryonic haematopoietic cell lineage, starting in the mesodermal area of the head around stage 10 of embryogenesis. Expression persists in hemocytes as embryonic development proceeds and the cells migrate posteriorly. In a fly strain carrying a deletion uncovering the DmVEGFR gene, hemocytes are still present, but their migration is hampered and the hemocytes remain mainly in the anterior end close to their origin. These data suggest that the VEGF/PDGF signalling system may regulate the migration of the Drosophila embryonic haemocyte precursor cells.

Alternative Splicing↗
PubMed2001

The interaction between ethanol and pregnanolone at induction of anaesthesia investigated with a threshold method in male rats.

1. An anaesthesia threshold was used to investigate the pharmacodynamic and pharmacokinetic interactions between ethanol and pregnanolone in male rats. 2. The criterion to determine threshold doses of pregnanolone was the first burst suppression of 1 s in the EEG. 3. Ethanol (0.5, 1.0, 1.5 and 2.0 g kg(-1)) was injected i.p. 15 min before pregnanolone infusion. Trunk blood, serum, cortex, cerebellum, hippocampus, striatum, brain stem, fat and muscle tissues obtained at criterion were used to determine ethanol (blood) and pregnanolone. Ethanol reduced threshold doses in a dose dependent linear manner. A similar reduction of pregnanolone tissue concentrations was only found in brain stem and striatum. Deviations consisted of larger decreases in serum, cerebellum and hippocampus after 0.5 g kg(-1) ethanol and in cerebellum, cortex and hippocampus after 2.0 g kg(-1) of ethanol. Positive correlations between dose and concentration of pregnanolone was recorded in brain stem, hippocampus, cerebellum and cortex. A kinetic component influenced the concentration in cortex. There was a correlation between dose and serum concentration of pregnanolone only after ethanol. In the muscle 0.5 g kg(-1) ethanol had no influence on pregnanolone concentration. 4. The linear, additive pharmacodynamic interaction could involve the GABA ionophore. A pharmacokinetic interaction was found in cortex. The retained high uptake of pregnanolone in muscle (after 0.5 g kg(-1)) corresponded to losses in other tissues (including serum). The reduced uptake of pregnanolone in cerebellum, cortex and hippocampus (after 2.0 g kg(-1)) was not due to a corresponding change in serum concentration. It was probably due to a reduced blood flow.

Anesthesia↗
PubMed2001

Inhibition of bacilli in industrial starches by nisin.

The properties of Bacillus coagulans and of other bacilli that contaminate paper and paperboard manufacturing processes were investigated under simulated industrial conditions. Nisin (0.05 to 0.125 microg ml(-1) blocked growth of indigenous bacilli that contaminate sizing starches. B. coagulans starch isolates, B. licheniformis, B. amyloliquefaciens, and B. stearothermophilus grew at > or = 50 degrees C in industrial starch and produced alpha-glucosidase and cyclodextrins. The industrial isolates and reference strains of B. amyloliquefaciens, B. cereus, B. coagulans, B. flexus, B. licheniformis, B. pumilus, B. sporothermodurans, B. stearothermophilus and Alicyclobacillus acidoterrestris were inhibited by < or = 0.125 microg of nisin on agar. B. coagulans and B. stearothermophilus were similarly inhibited by < or = 0.025 microg of nisin ml(-1) and by 3 microg of the biocide DBNPA ml(-1) in industrial starch. B. licheniformis and B. amyloliquefaciens strains were less sensitive. About 40% of nisin added to starch was retained after cooking. Fifty percent of the nisin remained active after 11 h of storage at 60 degrees C. The results show that nisin has potential as a preservative for modified industrial starches.

Anti-Bacterial Agents↗
PubMed2001

Evaluation and comparison of the pharmacokinetic and pharmacodynamic properties of allopregnanolone and pregnanolone at induction of anaesthesia in the male rat.

We have evaluated and compared the pharmacokinetic and pharmacodynamic properties of allopregnanolone and pregnanolone at induction of anaesthesia in male rats. A threshold method was used, and the first burst suppression period of 1 s or more in the EEG was selected as the end-point after fairly slow infusions. An optimal dose of 4.0 mg kg(-1) min(-1) was noted for both steroids. Brain concentrations were low at low infusion rates, indicating that acute tolerance was not occurring. Significant positive correlations were noted between dose rate and serum concentrations of allopregnanolone (r = 0.94, P<0.001) and pregnanolone (r = 0.88, P<0.001). Such correlations were also seen in striatum, cerebellum, cortex and muscle for both steroids (P<0.01). Despite changing infusion rates, the concentrations of both steroids in brainstem, hippocampus and fat remained stable. Because no correlation between infusion rate and steroid concentration was noted in the brainstem and hippocampus, these two brain areas may be regarded as primary sites of action for allopregnanolone and pregnanolone. Pregnanolone concentrations in the brainstem and hippocampus were significantly higher than those of allopregnanolone, suggesting that allopregnanolone was more potent than pregnanolone in inducing anaesthesia.

Anesthetics, Intravenous↗
PubMed1999

Inhibition of anandamide hydrolysis by the enantiomers of ibuprofen, ketorolac, and flurbiprofen.

The endogenous cannabimimetic anandamide is hydrolyzed by a fatty acid amide hydrolase to yield arachidonic acid and ethanolamine. In the present study, the regional distribution of the activity and its sensitivity to inhibition by the enantiomers of ibuprofen, ketorolac, and flurbiprofen has been investigated. The rate of [3H]anandamide hydrolysis was found in both 7-week-old and 90-week-old rats to be in the order hippocampus > cerebral cortex > cerebellum > striatum approximately midbrain, with higher rates of hydrolysis for the 7-week-old rats than for the 90-week-old rats. In whole brain (minus cerebellum), the R(-)-enantiomer of ibuprofen was a mixed-type inhibitor of anandamide hydrolysis and was approximately 2-3 times more potent than the S(+)-enantiomer, IC50 values of 230 and 750 microM, respectively, being found. A similar pattern of inhibition of anandamide hydrolysis was seen when intact C6 rat glioma cells were used. Ketorolac inhibited rat brain anandamide hydrolysis, with IC50 values of 50, 440, and 80 microM being found for the R-, S-, and R,S-forms, respectively. The IC50 value for R-flurbiprofen (60 microM) was similar to the IC50 value for the S-enantiomer (50 microM). These data demonstrate that there is no dramatic enantiomeric selectivity of NSAID compounds as inhibitors of fatty acid amide hydrolase enzyme(s) responsible for the hydrolysis of anandamide. The enantiomers of flurbiprofen and R-ketorolac are the most potent NSAID inhibitors of fatty acid amide hydrolase yet reported.

Aging↗
PubMed1999

Anaesthetic effects of pregnanolone in combination with allopregnanolone, thiopental, hexobarbital and flurazepam: an EEG study in the rat.

The anaesthetic interactions of the steroid, 3 alpha-hydroxy-5 beta-pregnan-20-one, in male rats were investigated in different fixed binary combinations with the steroid allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one), two barbiturates (thiopental and hexobarbital) and the benzodiazepine, flurazepam. Anaesthetic effects were determined using an EEG threshold method. Interactions were assessed using an isobolographic method. The interaction between the two steroids, pregnanolone and allopregnanolone, showed an anaesthetic effect significantly less than additive (antagonistic). The interactions between pregnanolone and the two barbiturates and the benzodiazepine showed an anaesthetic effect significantly greater than additive (potentiation) in all tests performed. These results could be explained by a pharmacodynamic interaction at the hypothetical GABA-benzodiazepine-barbiturate-steroid complex in the CNS.

Anesthetics, Combined↗
PubMed1999

A nisin bioassay based on bioluminescence.

A Lactococcus lactis subsp. lactis strain that can sense the bacteriocin nisin and transduce the signal into bioluminescence was constructed. By using this strain, a bioassay based on bioluminescence was developed for quantification of nisin, for detection of nisin in milk, and for identification of nisin-producing strains. As little as 0.0125 ng of nisin per ml was detected within 3 h by this bioluminescence assay. This detection limit was lower than in previously described methods.

Animals↗
PubMed1999

Physical dependence after benzodiazepine treatments in rats: Comparison of short and long treatments with diazepam and lorazepam.

OBJECTIVE: This study examined the development of physical dependence after different durations of treatments with two benzodiazepines (diazepam and lorazepam). METHOD: Increased excitation in the central nervous system during a 2-week withdrawal period after 4-day and 4-week treatments with diazepam and lorazepam was examined with an EEG threshold method in male rats. Increased excitation was measured as a decreased sensitivity to hexobarbital (i.e., increased threshold doses). The concentrations of hexobarbital in two different brain regions, serum, fat and muscle tissue after 4-week treatment with diazepam were determined with a high-pressure liquid chromatography method. RESULTS: The duration of withdrawal was influenced by the duration of treatment but the maximum level of withdrawal excitation was similar for both drugs. Equieffective doses of diazepam (20 mg/kg) and lorazepam (2 mg/kg) induced similar patterns of withdrawal excitability after both treatments. The brain concentrations of hexobarbital were significantly higher on Days 1 and 3 of withdrawal after diazepam treatment. Significant correlations between the threshold doses and brain concentrations were found on Day 1, but these correlations disappeared on day 3. At the same time, a difference between the concentrations of hexobarbital in different brain areas emerged. CONCLUSIONS: The duration of treatment had a minor influence on the pattern of withdrawal excitation. Equieffective doses of diazepam and lorazepam induced comparable withdrawal excitability indicating no significant difference in their potential to induce physical dependence. The time-dependent change in the hexobarbital concentrations in the brain suggests that withdrawal excitation after diazepam treatment is a complex phenomenon probably involving several different systems at different times.

Animals↗
PubMed1999

Acute and long term effects of buspirone treatments on voluntary ethanol intake in a rat model of alcoholism.

Buspirone, a 5-HT1A agonist, has been shown to decrease the intake of ethanol when given as a single dose to rats with a psychological dependence induced according to our rat model of alcoholism. The present experiment evaluates the effects different treatments with buspirone have on voluntary ethanol intake in these psychologically dependent rats. As a first treatment, buspirone was given once daily for 23 days at the dose of 20 mg/kg/day. Ethanol was withheld except for the first and the last day of the treatment. On the first day, the buspirone injection decreased ethanol intake from the pretreatment value (1.94+/-0.18 g/kg/day), down to 1.36+/-0.18 g/kg (p < 0.01, n = 12). The rats were again given a choice between water and 10% ethanol after the last injection of buspirone. During the following 24 hr period, the ethanol intake was increased to 3.56+/-0.24 g/kg/day (p < 0.001 vs. the pretreatment intake, n = 12). A loss of correlation with the pretreatment intake of ethanol indicated an altered regulation of ethanol intake for approximately 3 more weeks. Fifteen weeks after the start of the first treatment, buspirone (20 mg/kg) was re-tested as a single dose, with no effect on ethanol intake. Twenty-two weeks after the start of the first treatment, a 1-week treatment with 20 mg/kg/day of buspirone was started. During this treatment, the rats had a continuous choice between 10% ethanol and water. There was, as in the first re-test, no effect on ethanol intake on the first day of the treatment. However, on the last 2 days of the treatment, the ethanol intake was increased to 2.86+/-0.28 g/kg and to 2.89+/-0.26 g/kg respectively (p < 0.05, n = 10 on both days, compared with the pretreatment intake of 1.78+/-0.36 g/kg). Thus, an acute dose of buspirone can decrease voluntary ethanol intake in psychologically dependent rats, but long-lasting changes in the effect of buspirone seem to develop during a 3-week treatment period.

Alcohol Drinking↗
PubMed1998

Age-dependent changes in adenosine receptors are not modified by life-long intermittent alcohol administration.

Autoradiography and in situ hybridisation were used to examine age-dependent changes in adenosine receptors in male rats and to determine if life-long (94 weeks) intermittent ethanol consumption had any additional effect. Adenosine A2A receptors in striatum, as assessed by [3H]CGS 21680 binding, decreased by approximately 20% between the ages 6 and 99 weeks. Since dopamine D2 receptors and the mRNA for preproenkephalin also decreased there appears to be a loss of A2A-D2 receptor-bearing striatopallidal cells. Life-long ethanol consumption had no additional effect. Adenosine A1 receptors, as determined by [3H]DPCPX binding, did not decrease with age in any region of the brain, but increased slightly in the cerebellum. In substantia nigra, the increase in [3H]DPCPX binding upon addition of GTP was eliminated. Surprisingly, the amount of A1 receptor mRNA decreased significantly with age in most of the examined regions, including the cerebellum. There was no additional effect of ethanol treatment. It is suggested that age alters the number of cells that express A2A receptors, the turnover of A1 receptors, and in some regions their coupling to G proteins, but that life-long intermittent ethanol exposure has little additional effect.

Aging↗
PubMed1998

A study of the duration of acute tolerance induced with hexobarbital in male rats.

Male rats were infused i.v. with hexobarbital to obtain a burst suppression of 1 s or more in the EEG (SS). At SS the rats were killed and the concentration of hexobarbital was determined by HPLC in three parts of the brain. Acute tolerance (induced by a 1-h exposure at the SS level) was recorded as an approximately 20% increase in brain concentrations of hexobarbital at the last SS during the exposure when compared with concentrations recorded at the first SS in the controls. Increased brain concentrations (approximately 8%) at SS were recorded 24 h after induction of acute tolerance. After 48 h the increase was uncertain. Thus, acute tolerance to hexobarbital could have cumulative properties if new exposures are imposed after 24 h.

Animals↗
PubMed1998

Citalopram as an inhibitor of voluntary ethanol intake in the male rat.

Psychological dependence was induced in rats by a 1-year intermittent exposure to intoxicating doses of ethanol, and recorded by the rat's ability to later take the same dose of ethanol independent of the offered concentration. Citalopram (10 or 40 mg/kg/day) was given for 3 weeks with ethanol available only the first and the last day; 10 mg/kg had no effect. On the first treatment day 40 mg/kg decreased ethanol intake. On the last treatment day 40 mg/kg had no effect. The following week the ethanol intake was higher than before the treatment in the 40 mg/kg group. During the four posttreatment weeks the ethanol intake of the 40 mg/kg group dropped significantly. Citalopram was retested 18 weeks after the first treatment during 1 week, with continuous access to ethanol; 10 mg/kg had no effect and 40 mg/kg decreased ethanol intake at day 1, reaching a minimum in day 3. A tolerance to this effect was seen at the end of the week. Thus, in this model an acute dose of citalopram can decrease ethanol intake, but tolerance to this effect develops when citalopram is given both with and without access to ethanol.

Alcoholism↗
PubMed1998

Development of physical dependence to lorazepam in rats: the effects of repeated short treatments, dose and age.

Rats were treated with lorazepam for four days (six times 2 mg kg(-1)) at the ages of 71, 118, 163 and 210 days. Increased excitation (physical dependence) in the withdrawal period was tested several times during 14 days with hexobarbital in an EEG threshold test. Lorazepam could induce physical dependence usually with a maximum (20% of the controls) on day four of withdrawal, but the age was a critical variable. A dose-response relationship with regard to lorazepam (0.5, 1, 2 mg kg(-1)) was found at 71 days but a more complicated pattern was found at 118 days of age. The rats treated with lorazepam 2 mg kg(-1) at the ages of either 71 and 118 days were given a treatment again with lorazepam 2 mg kg(-1) three months later. Compared with age-matched untreated rats, previous drug exposure influenced the pattern of increased excitation indicating a carry-over effect even after such a recovery period.

Age Factors↗