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Biomedical subjects

L Nyberg

Publications and source records attributed to L Nyberg.

At least 91 records · Page 5Linked to original sources

Valuable indicators of physical stress in porcine plasma.

Various markers for stress were evaluated in the plasma of pigs. Treadmill exercise was chosen as a well defined and quantifiable stressor. One group of non-stress-susceptible pigs had to carry out two intense exercise bouts at a one-week interval, and another group remained in their pens and served as controls. Large interindividual differences in the performance and in the hormonal and metabolic responses to exercise were observed. The exercise stress resulted in an immediate increase in the plasma concentrations of cortisol, lactate and hypoxanthine, with a return to the pre-exercise levels within one hour. No direct effect of physical stress on CBG binding capacity or on the concentrations of xanthine and uric acid was observed. In two very nervous pigs, even mild stress in connection with the first blood sampling resulted in an elevated concentration of lactate, but the cortisol and hypoxanthine values remained at the basal level. It is concluded that plasma concentrations of cortisol, lactate and hypoxanthine are valuable markers for physical stress.

Animals↗

The effect of thiopentone-sodium anesthesia and surgery, relocation, grouping, and hydrocortisone treatment on the blood levels of cortisol, corticosteroid-binding globulin, and catecholamines in pigs.

Eight crossbred, ovariectomized gilts (Swedish Landrace x Swedish Yorkshire x Hampshire), with a mean age of 7.5 mo, were studied during anesthesia and surgery, control-sampling, relocation, and grouping during a period of 3 wk. Acute treatment with a hydrocortisone injection (5 mg, i.v.) was also given. Blood samples were taken frequently (every 10 min) during the intensive part of the experimental days. The blood samples were analyzed for catecholamines (CA), adrenaline (A) and noradrenaline (NA), cortisol, and corticosteroid-binding globulin (CBG). The surgical period with anesthesia and surgery showed significant effects on CA, cortisol, and CBG. The A level increased immediately after the surgery. A biphasic increase in the cortisol level was observed on the day of surgery; the greatest increase was seen when the animals had regained consciousness after surgery but still were drowsy and staggering. The CBG level decreased on the day after the surgery. The study showed that the levels of the analyzed substances were back to normal 2 d after surgery. During relocation and grouping there was a short, significant increase in CA and cortisol levels, whereas the CBG level was not affected. Treatment with hydrocortisone significantly increased the cortisol level, but no change was seen in plasma CA or CBG levels. In conclusion, anesthesia and surgery induced significant effects on the levels of CA, cortisol, and CBG in gilts and the animals needed 2 d to recover before regaining their normal condition. During relocation and a limited grouping period, the significant increases in CA and cortisol levels were of short duration and CBG did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

The effect of transport stress on plasma levels of catecholamines, cortisol, corticosteroid-binding globulin, blood cell count, and lymphocyte proliferation in pigs.

The effect of transport stress on the plasma levels of catecholamines, cortisol, and corticosteroid-binding globulin were studied in 6 gilts. To assess the effect on immune status, white blood cells were also counted and the cell-mediated immunity was estimated. The adrenaline level increased significantly during transport, from a basal mean level of 0.03 ng/ml to a plateau level of 0.11 to 0.12 ng/ml. The noradrenaline level fluctuated, but not constantly, during transport. The mean plasma cortisol level before loading was approximately 40 nmol/l and rose immediately after the start of transport to 70 nmol/l (p < 0.05) and to 87 nmol/l (p < 0.01) within 10 and 30 min, respectively. After unloading the cortisol level rapidly decreased and a minimum level was seen 4 h after the transport, whereafter the diurnal rhythm was resumed. The plasma corticosteroid-binding globulin level increased nonsignificantly during the day of transport, from 25 nmol/l to a level of 34 nmol/l, and it continued to increase until a plateau level was reached on the second day after transportation. The total white blood cell number increased significantly (from 13.7 to 15.5 x 10(9) cells/l), the number of lymphocytes decreased significantly (from 8.4 to 7.0 x 10(9) cells/l), and the number of polymorphonuclear neutrophils increased significantly (from 4.3 to 7.2 x 10(9) cells/l) during transport. No significant variation in the proliferation response was seen in the whole blood cell cultures. The main results were the significant signs of simultaneous activity of both the adrenal cortex and the adrenal medulla during transport.

Animals↗

Cortisol binding capacity of corticosteroid binding globulin in hyperadrenocorticoid and healthy dogs.

Corticosteroid binding globulin (CBG) binding capacity and plasma cortisol concentration were determined in 27 dogs with hyperadrenocorticism and in 17 healthy control dogs. Cortisol concentrations were significantly higher in hyperadrenocorticoid dogs than in controls. CBG binding capacity did not differ between the two groups. It is concluded that excessive endogenous cortisol secretion does not induce an increase in CBG binding capacity. Consequently, the determination of CBG binding capacity provides no additional information for the diagnosis of canine Cushing's syndrome.

Animals↗

Swedish norms for completion of word stems and unique word fragments.

Swedish norms for completion of word stems and single-solution word fragments, with few or many letters specified, were obtained from Swedish students. Comparisons were made for completion rates between stems and fragments that were possible to complete with the same word. As expected, completion rates for fragments were generally superior to those of word stems since the word stems allowed alternative completions. Adding one letter to the word stems and fragments resulted in a significant increase in the probability of completion, for both stems and fragments. A stepwise regression analysis was conducted in order to partial out factors determining the completion probability for fragments. The ratio of specified letters to blank characters, and the familiarity of the solution was found to be the most important factors. Finally, the effect of number of given letters in the word stem on the number of generated words per stem was studied. The mean number of words generated per stem was found to be equal for both two- and three-letter word stems.

Adolescent↗

Characterization of the murine corticosteroid binding globulin: variations between mammalian forms.

Corticosteroid binding globulin (CGB) from term-pregnant mouse serum was isolated and characterized by peptide analysis after treatment with CNBr and Lys-specific protease, respectively. Amino acid sequence analysis of six segments, covering 189 of 383 positions in different regions of the protein, showed unexpectedly low overall homology (60%) to the indirectly deduced human amino acid sequence previously reported. However, some segments displayed a greater resemblance to their human counterparts. Differences were observed in at least two of six potential glycosylation sites. The nature of electrophoretic CBG variants and their immunological properties are described.

Amino Acid Sequence↗

Pharmacokinetic evaluation in man of terbutaline given as separate enantiomers and as the racemate.

1. The pharmacokinetics of the two enantiomers of terbutaline, (+)T and (-)T, and the racemate (+/-)T, have been evaluated after single intravenous and oral dosage to six healthy volunteers. 2. The mean systemic clearance, CL, was 0.19 and 0.13 l h-1 kg-1 for (+)T and (-)T, respectively. This difference was statistically significant. The mean clearance of (+/-)T was 0.20 l h-1 kg-1. Volumes of distribution were similar (1.9 l kg-1) after the three intravenous administrations. The differences in CL were reflected in values of the elimination half-life and MRT. 3. The difference in CL of the isomers could be explained by a corresponding difference in their renal clearance, CLR. Competition for stereoselective active reabsorption in the tubule might explain why (+)T seemed to enhance the CLR of (-)T when the drug was given as the racemate. 4. Oral bioavailability, calculated from plasma data, of (+)T was 7.5% and that of (-)T was 14.8%. This difference was statistically significant and was mainly due to a difference in absorption of (+)T and (-)T, but also to a difference in their subsequent first-pass metabolism. The bioavailability of (+/-)T was similar to that of (-)T. 5. (-)T appears to govern the absorption properties of the racemate, while (+)T determines its elimination behaviour. Systemic metabolism of the two enantiomers was similar and, therefore, a greater first-pass metabolism of (+)T would reflect a higher capacity of the gut wall to metabolise this isomer.

Absorption↗

Absorption of drugs from continent caecal reservoir for urine.

The possibility of drug absorption from a continent caecal reservoir for urine was studied in 3 men with well functioning reservoirs. Saline solutions of digoxin, theophylline or terbutaline were instilled into the reservoir, each on a separate occasion, and drug concentrations in plasma and urine were measured for 24 h thereafter. Theophylline, but not terbutaline or digoxin, was absorbed from the reservoir. Estimated from an intravenous reference dose, the uptake of theophylline from the reservoir was approximately 50%. In patients with this type of urinary diversion, therefore, reabsorption from the continent caecal reservoir may complicate drug therapy.

Aged↗

Pharmacokinetics of intravenous terbutaline in asthmatic children.

Seven asthmatic children were given terbutaline intravenously. The intact drug was measured in plasma and urine, and its conjugates were measured in urine. The decreasing plasma concentrations of terbutaline did not attain a terminal slope until 8-12 h after dosing. This was most likely due to different kinetics of the enantiomers. The terminal half-life was 8.8-15.8 h. Body clearance was 2.73-5.44 ml/min/kg, two-thirds of which were of renal origin. The volume of distribution (Vss) was 1.28-1.83 l/kg. The disposition pharmacokinetics of terbutaline do not rationalize a higher dose per kg body weight in children than in adults.

Asthma↗

A simple method for the purification of murine corticosteroid binding globulin: characterization of a monomer.

A fast and reproducible two-step method with high resolution was developed for purification of murine corticosteroid-binding globulin (CBG). The first step was liquid chromatography on a Sephacryl-S-200 column, and the CBG-containing residual was subsequently chromatographed by fast protein liquid chromatography (FPLC). This enabled us to quickly obtain a highly purified protein and the apparently isolated CBG was tested for its purity by sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis (SDS-PAGE) and sedimentation equilibrium centrifugation. The CBG concentration in pregnant mouse serum was estimated to 0.78 g/l (1.5% of the total protein). The monomeric organization of the protein was demonstrated by mercaptoethanol treatment. No NH2-terminal amino acid could be detected, probably owing to a blocked amino acid. The mol. wt (Mr) of murine CBG was determined to be 52,000 and the sedimentation constant S20 degrees, w to 3.9 S by analytical ultracentrifugation. The protein showed 5 bands when subjected to isoelectric focusing: 3 bands with apparent isoelectric points (pI) between pH 3.15-3.25 and two between pH 3.40-3.50.

Amino Acids↗

Effects of transport stress on concentrations of cortisol, corticosteroid-binding globulin and glucocorticoid receptors in pigs with different halothane genotypes.

Effects of stress on concentrations of cortisol and corticosteroid-binding globulin (CBG) in blood plasma and on glucocorticoid receptor concentrations in muscle cytosol were studied in pigs representing three Halothane (Hal) genotypes (NN, Nn, nn). At 12 wk of age, animals were divided into four groups: pigs subjected to transport (5 h in a truck), pigs treated with amperozide prior to transport, pigs not transported but treated with amperozide and pigs neither transported nor given amperozide. Animals were slaughtered the week they reached 100 kg live weight (3 mo later). The Hal gene showed no major influence on the variables studied except for cortisol concentrations (P = .06) measured directly after transport at 12 wk of age (NN = 66.8 nM, Nn = 61.4 nM, nn = 69.4 nM). However, the response in each Hal genotype differed, depending on whether or not the pigs had been exposed to transport. Two weeks after transport, NN pigs developed higher cortisol concentrations than untransported animals, whereas the response was reversed in nn animals; Nn pigs showed no difference in this regard. At slaughter, the effect of transport (12 wk of age) on cortisol and CBG was still apparent. In NN pigs cortisol and CBG concentrations were elevated (P less than or equal to .05, P = .08, respectively), whereas concentrations tended to be lower in nn pigs (P = .17, P = .07, respectively) when compared with untransported pigs. Transported pigs had lower receptor concentrations at slaughter (P less than or equal to .01) than untransported pigs. However, pigs given amperozide in connection with transport had a receptor concentration comparable to that in untransported pigs. Our study shows conclusively that transport stress had long-term effects on cortisol, CBG and glucocorticoid receptor concentrations. In addition, amperozide had long-term effects on cortisol and receptor concentrations.

Animals↗

Influence of the Hal locus and standardized stress on antibody response and in vitro reactivity of peripheral blood lymphocytes in pigs.

The antibody response to two Escherichia coli antigens (O149 and K88) and the in vitro reactivity of peripheral blood lymphocytes (PBLs) to pokeweed mitogen was studied in growing pigs after exposure to varying degrees of stress. Three experimental groups were used; transportation by lorry, transportation by lorry after a previous injection of a tranquillizing drug (amperozide), no transportation but an amperozide injection. Another group was used as a control group. This group was not transported and received no amperozide injection. The animals were the offspring of boars and sows heterozygous (Nn) for the Hal gene, and all 3 Hal genotypes (NN, Nn, nn) were identified and could thus be compared within litters. Immediately after the experimental treatment, the highest PBL reactivity was found for the amperozide-treated animals and for the non-transported animals, with no differences in reactivity between Hal genotypes. Two weeks later, the treatments caused different effects on pigs of the 3 Hal genotypes, both with regard to the PBL reactivity and the IgG response to O149. The NN pigs had a higher PBL reactivity than the nn pigs for all treatments except the 'drug + transport' class where the reverse rank order was found. The NN pigs also had a higher IgG response to O149 than the nn pigs in the 'drug + no transport' class. The amperozide treatment was followed by a higher PBL reactivity in non-transported NN pigs and in transported nn pigs. The amperozide-treated non-transported NN pigs also had a higher IgG response to O149. The highest PBL reactivity and IgG response to O149 were found mainly in pigs with the lowest cortisol levels. Pronounced differences between litters were found for both the antibody response and the PBL reactivity.

Anesthesia↗

Effects of ACTH on the ligand-binding properties of the glucocorticoid receptor exerted not only via elevated levels of corticosteroids.

Treatment of mice with ACTH not only increased plasma corticosterone levels, but also reduced the ligand-binding capacity of the glucocorticoid receptor in skeletal muscle cytosol. Non-linear Scatchard plots were obtained for the glucocorticoid receptor following ACTH treatment. This upward concave curvilinearity could not be reproduced by simply adding to the cytosol an amount of corticosterone corresponding to the increase, even though this treatment resulted in reduced binding capacity. The addition of corticosterone resulted in a slower formation of ligand-receptor complexes (lower association rate constant), which offered a partial explanation for the low binding. In addition, ACTH treatment was also found to reduce the binding capacity in adrenalectomized mice that did not respond with corticosterone elevation. However, in this case Scatchard plots were linear.

Adrenalectomy↗

Ontogenetic development of serotoninergic neurons in the brain of a teleost, the three-spined stickleback. An immunohistochemical analysis.

The ontogenetic development of serotoninergic neurons in the brain of the stickleback was investigated with the indirect immunocytochemical peroxidase-antiperoxidase technique, using a specific antibody to serotonin (5-hydroxytryptamine, 5-HT). Formation of neuronal populations takes place during embryonic development. By 80 h after fertilization, the first 5-HT perikarya have appeared in the ventricular zone of the hypothalamus (nucleus recessus lateralis) and the raphe region. At 108 h the first 5-HT perikarya can be observed in area praetectalis. At 118 h a transient group of 5-HT neurons appears rostral to the nucleus recessus lateralis, and at this same age the first 5-HT perikarya may be visualized in nucleus recessus posterioris. A group of 5-HT neurons appears in the dorsolateral tegmentum at 166 h (one day after hatching, which occurs at 120-144 h after fertilization). Differentiation of the neuronal populations, in terms of migration and formation of subdivisions, starts between 80 h and 94 h, and seems to be completed between 1 and 5 days after hatching. Raphe nuclei form an anterior group comprising nuclei raphe dorsalis, raphe medialis and a ventrolateral group, and a posterior group comprising a nucleus raphe pallidus/obscurus complex, a lateral nucleus reticularis paragigantocellularis and a ventromedial nucleus raphe magnus. The posterior and ventral raphe nuclei, which are well developed at the time of hatching, have not been visualized in the adult stickleback. While formation of 5-HT neuronal systems, as well as their primary efferent pathways, takes place during early ontogenetic development, the establishment of terminal areas and their subsequent differentiation apparently takes place during later ontogenetic stages. Most presumptive target areas are penetrated by 5-HT axons at hatching, although terminal formation does not seem to start until later. A considerable number of 5-HT neuronal groups present in the embryonic and newly hatched stickleback have not been visualized in the adult stickleback. This may be due to selective cell death, changes in transmitter phenotype or maturation of axonal transport processes during development.

Animals↗

Serotonin and opsin immunoreactivities in the developing pineal organ of the three-spined stickleback, Gasterosteus aculeatus L.

5-hydroxytryptamine (5-HT, serotonin)- and opsin-immunoreactive sites were studied in the developing pineal complex of the stickleback, Gasterosteus aculeatus L., by use of light-microscopic indirect immunoperoxidase techniques. 5-HT immunoreactivity first occurs in the pineal organ at the age of 80 h after fertilization and appears to be localized in cells of the photoreceptor type. The outer segments of a few pineal photosensory cells exhibit opsin immunoreactivity at the age of 84 h after fertilization. The number of cells seems to increase until the pineal organ is completely developed. The increase in the number of 5-HT immunoreactive perikarya runs parallel in time to that of the opsin-immunoreactive outer segments. The cells of the parapineal organ show neither opsin nor 5-HT immunoreactivity. The retina of the embryonic stickleback does not display opsin immunoreactivity until after hatching, which takes place about 144 h after fertilization. These results suggest, in the three-spined stickleback, an earlier light-perception capacity for the developing pineal organ than for the retina.

Animals↗

Pharmacokinetics of terbutaline given in slow-release tablets.

Three pharmacokinetic studies of terbutaline slow-release (SR) tablets, 5 and 7.5 mg, were performed in healthy subjects. Four men and 4 women volunteered for each study. Bricanyl plain tablets were used as reference formulation. Both single- and multiple-dose treatments were performed. For repeated administration, SR tablets were given every 12 h. Plain tablets were given every 8 h in two studies and every 12 h in one. Steady-state bioavailability correlated with the amount dissolved in vitro (paddle method) in 6 h. Single-dose bioavailability was limited by the amount dissolved in 4 h. The difference may have a pharmacological explanation, in that repeated administration of a sympathomimetic drug is known to decrease gastro-intestinal motility. Tablets of both strengths with an intermediate dissolution rate were extensively tested. Plasma concentrations and the rates of urinary excretion of unchanged terbutaline were measured. Mean relative bioavailability compared with plain tablets was 76-77% with 7.5 mg SR tablets and 74-80% with those of 5 mg. Variation in bioavailability between and within subjects was the same or smaller with the SR tablets. They gave smoother plasma concentration profiles with delayed peaks and the same peak/trough concentration ratios as the plain tablets, despite less frequent dosing. However, objectively measured side-effects were not significantly reduced. Measurements after cessation of treatment gave terminal half-lives in plasma of 11.5-23.0 h which is considerably longer than reported in the literature. Renal clearance averaged 140 mL/min, similar to predicted creatinine clearance. From these studies it is concluded that the main advantage with the SR tablets is the twice-daily dosage regimen. This should increase compliance, facilitate combination therapy with prolonged-action formulations of other drugs and better maintain therapeutic levels during the whole night interval.

Adult↗