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H Axelsson

Publications and source records attributed to H Axelsson.

At least 19 recordsLinked to original sources
PubMed2003

Rates of metabolism of chlorzoxazone, dextromethorphan, 7-ethoxycoumarin, imipramine, quinidine, testosterone and verapamil by fresh and cryopreserved rat liver slices, and some comparisons with microsomes.

In the present study we have investigated the disappearance of chlorzoxazone, dextromethorphan, 7-ethoxycoumarin, imipramine, quinidine, testosterone and verapamil from the medium in which fresh and cryopreserved rat liver slices were incubated. These compounds are all substrates of major isoforms of cytochrome P450 expressed in the liver. The metabolism of five of these compounds in microsomes from rat liver was also examined. Determinations of the concentrations of the compounds were performed employing LC/MS. Intrinsic clearance values (CL(ints)) were calculated on the basis of the concentration-vs.-time curves. No significant differences in the CL(int) values obtained with fresh and cryopreserved rat liver slices were observed for any of the compounds. The highest CL(int) value estimated with liver slices was observed for testosterone and the lowest values were with chlorzoxazone and 7-ethoxycoumarin. The total CL(int) values for 7-ethoxycoumarin and imipramine, calculated using scaling factors, were similar for liver slices and microsomes. In the case of testosterone, this total CL(int) was approximately 3.7-fold lower, whereas for dextromethorphan and quinidine it was 2.5- and 8.5-fold higher, respectively, with liver slices than with microromes. In conclusion, the rate of metabolism of the seven compounds tested with rat liver slices was not affected by cryopreservation. This finding adds further support to the general conclusion that the major activities involved in drug metabolism are not affected by cryopreservation of rat liver slices.

Animals↗
PubMed2000

Experimental cancer cachexia: the role of host-derived cytokines interleukin (IL)-6, IL-12, interferon-gamma, and tumor necrosis factor alpha evaluated in gene knockout, tumor-bearing mice on C57 Bl background and eicosanoid-dependent cachexia.

MCG 101 tumors were implanted sc. on wild-type C57 Bl and gene knockout mice to evaluate the role of host-produced cytokines [interleukin (IL)-6, IL-12, IFNgamma, tumor necrosis factor (TNF) receptor 1, and TNF receptor 2] to explain local tumor growth, anorexia, and carcass weight loss in a well-defined model with experimental cachexia. Indomethacin was provided in the drinking water to explore interactions between host and tumor-derived prostaglandins and proinflammatory cytokines for tumor growth. Wild-type tumor-bearing mice developed cachexia because of rapid tumor growth, which were both attenuated in IL-6 gene knockouts. Similar findings were observed after provision of anti-IL-6 to wild-type tumor-bearing mice. Alterations in food intake were not directly related to systemic IL-6 but rather secondarily to IL-6-dependent tumor growth. The absence of host-derived IL-12, IFN-gamma, or the TNF receptor 1 or receptor 2 gene did not attenuate tumor growth or improve subsequent cachexia. Thus, carcass weight loss was not improved by the omission of host cytokine (TNF-alpha, IL-12, or IFN-gamma) except for IL-6. Systemic indomethacin provision decreased plasma prostaglandin E2 in five of six groups of gene knockout tumor-bearing mice, which was associated with improved carcass weight in these groups. Indomethacin seemed to improve food intake to a similar extent in both wild-type and gene knockouts, which agree with the speculation that eicosanoids are more important to explain anorexia than host cytokines. Our results demonstrate that host- and tumor-derived cytokines and prostaglandins interact with tumor growth and promote cachexia in a more complex fashion than usually presented based on previous information in studies on either anti-cytokine experiments in vivo or on gene knockouts with respect to a "single cytokine model." Overall, host cytokines were quantitatively less important than tumor-derived cytokines to explain net tumor growth, which indirectly explains subsequent cachexia and anorexia.

Animals↗
PubMed2000

Neuroendocrine peptide levels in the gastrointestinal tract of mice after unilateral cervical vagotomy.

The effects of left and right unilateral cervical vagotomy on the content of several neuroendocrine peptides were studied in different parts of the murine gastrointestinal tract, known to receive vagal innervation. The neuroendocrine peptides investigated were secretin, gastric inhibitory peptide (GIP), gastrin, motilin, peptide YY (PYY), somatostatin, substance P, VIP, neurotensin, neuropeptide Y (NPY), and galanin. The neuroendocrine peptide concentration was affected after both left and right vagotomy, and that the changes in the concentrations of the neuroendocrine peptide levels occurred in all the gastrointestinal segments investigated, namely antrum, small and large intestine. However, these changes varied, depending on which side was vagotomized and the interval after vagotomy. It is concluded that the vagus nerve had an important impact on the neuroendocrine system in the murine gut. It is suggested, furthermore that the contradictory results obtained earlier on the effect of vagotomy on the gastrointestinal peptides may depend on differences in the vagotomy methods used and on differences in observation time after vagotomy.

Animals↗
PubMed2000

Physiological changes in pigs exposed to a blast wave from a detonating high-explosive charge.

The aim of this project was to study respiration, circulation, and brain activity in pigs during and after a blast wave exposure. Ten anesthetized pigs were used. Seven were exposed to blast and three were controls. Physiological parameters of respiration and circulation as well as cortical activity were followed from 30 minutes before until 120 minutes after the real or simulated blast. There were no significant changes in heart rhythm, cardiac output, arterial oxygen or carbon dioxide tension, blood pH, or mixed venous saturation during the experiment. The blast exposure caused intestinal injuries but no lung damage. A transient flattening of the electroencephalogram was seen immediately after the blast in four experimental animals, in contrast to the unchanged baseline electroencephalogram of the control animals. This momentary depression of cortical activity accompanied by short-lasting apnea indicates a blast wave-induced effect on the brainstem or higher controlling center.

Animals↗
PubMed1999

Diaphragmatic activity after laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy is presumed to induce a reduction in diaphragmatic activity. Indirect indices of diaphragmatic function based on tidal changes in pressures and cross-section area measurements can be unreliable in the postoperative phase. The present study evaluates diaphragmatic activity by directly recording diaphragmatic EMG (EMGdia) data, along with indirect indices. METHODS: Thirteen adult patients (American Society of Anesthesiologists physical status I or II) undergoing laparoscopic cholecystectomy were examined preoperatively for inspiratory tidal changes in gastric (Pgas-insp) and esophageal (Peso-insp) pressures, and tidal changes in ribcage (Vthor) and abdominal (Vabd) cross-section areas and then again at 1, 6, and 24 h postoperatively combined with EMGdia recordings. Variations in inspiratory gastric (deltaPgas-insp) and inspiratory transdiaphragmatic (deltaPdi-insp) pressures were derived from the above. RESULTS: Laparoscopic cholecystectomy induced a significant reduction in mean deltaPgas-insp, mean deltaPdi-insp, and mean Vabd indicating a reduction of diaphragmatic activity postoperatively. DeltaPdi-insp decreased from 11.8+/-4.0 cm H2O preoperatively to 5.7+/-5.7 cm H2O at 1 h and 6.6+/-5.1 cm H2O at 6 h postoperatively (mean +/- SD; P < 0.05). Vabd decreased from 327.0+/-113.0 ml preoperatively to 174.0+/-65.0 ml at 1 h and 175.0+/-98.0 ml at 6 h postoperatively (mean +/- SD; P < 0.05). These values had partially recovered at 24 h. CONCLUSION: The direct and indirect indices of diaphragmatic activity taken together confirm the presence of reduction in diaphragmatic activity after laparoscopic cholecystectomy followed by its partial recovery at 24 h.

Adult↗
PubMed1999

Changes in intestinal endocrine cells in the mouse after unilateral cervical vagotomy.

The effect of right or left unilateral cervical vagotomy on the intestinal endocrine cells was studied in 23 mice at 2 and 8 weeks after operation, respectively. The results were compared with that from 10 sham operated mice. Various types of endocrine cells in duodenum and proximal colon were detected by immunohistochemistry and quantified by computerized image analysis. In mouse duodenum, chromogranin-, CCK/gastrin-, GIP- and somatostatin-cells were significantly decreased at 2 weeks after right vagotomy, but returned to the control levels at 8 weeks. Serotonin-cells were reduced at both 2 and 8 weeks after right vagotomy. The amount of the duodenal endocrine cells did not change after left vagotomy with the exception of secretin-cells, which were diminished at 8 weeks after both right and left vagotomy. In the proximal colon, chromogranin-cells were also decreased at 2 weeks after right vagotomy. Serotonin-cells were reduced at 8 weeks after left vagotomy but not right vagotomy. There was no significant difference between the unilaterally vagotomized and the sham operated mice with regard to PYY- and glucagon-cells. It was concluded that vagotomy affected the intestinal endocrine cells in mouse. The influence was more pronounced in the small intestine than the proximal colon. The right vagus nerves seemed to exert more effect on the intestinal endocrine cells than the left ones.

Animals↗
PubMed1999

Effects of unilateral cervical vagotomy on antral endocrine cells in mouse.

The present study was carried out to investigate the effect of unilateral cervical vagotomy on the antral endocrine cells in mouse. Fifty-four mice were randomly divided into three groups, 18 in each, for left or right cervical vagotomy, or sham operation as controls. The animals were sacrificed 2, 4, and 8 weeks after the operation, respectively. Chromogranin-, gastrin/CCK-, serotonin-, and somatostatin-cells were detected by immunohistochemistry and quantitated by computerised image analysis. The results showed that the number of chromogranin-cells was decreased in both left and right vagotomized mice after 4 weeks and remained at the same level after 8 weeks. The numbers of gastrin-, serotonin- and somatostatin-cells did not change after right vagotomy. However, the numbers of gastrin- and somatostatin-cells were decreased after left vagotomy, whereas no change was found in serotonin-cells. Endocrine cells with vacuolated cytoplasm and pyknotic nuclei were also observed during the course of time. The alteration in the antral endocrine cells observed in this study seemed to be dynamic and depended on the observation time after the operation as well as the denervated branches of the vagus nerve. This may explain, at least partially the contradictory results obtained earlier by different investigators.

Animals↗
PubMed1998

Life expectancy and cost utility after total hip replacement.

In a prospective study of 410 cemented hip replacements in 372 patients with a mean age of 71 years, mortality after 8 years was 33%. Mortality for patients with osteoarthrosis was lower than in an age matched control population, probably because of a preoperative selection of patients. An estimate of costs and adjusted quality of life has shown that total hip replacement has a good cost utility even in the elderly patient. The conclusion of this study is that the indications for hip replacement in the elderly patient can be expanded. Such patients should undergo surgery earlier in the course of their disease.

Adult↗
PubMed1996

Chest wall velocity as a predictor of nonauditory blast injury in a complex wave environment.

Previous blast injury prediction criteria have been based on exposure to classic Friedlander or ideal blast waves. An ideal waveform is characterized by an instantaneous rise to a peak overpressure that decays exponentially to ambient pressure followed by a negative phase. The prediction criteria did not address injuries resulting from exposure to complex blast waves. It was difficult to establish a simple relationship between the two because complex blast waves typically consist of multiple shocks with variable frequency content and intensity that may be superimposed on a slow rising quasistatic pressure pulse. This paper deals with the application of a single degree of freedom mathematical model, originally developed to measure the response of the thorax to Friedlander waves, to calculate chest wall velocities resulting from various complex blast loads. Experimental results with sheep, exposed to complex blast waves in enclosures, demonstrated that there was a good relationship between the Adjusted Severity of Injury Index (which includes injury to the lungs, upper respiratory tract, gastrointestinal tract and solid intraabdominal organs) and the calculated peak inward chest wall velocity. In addition, there was a good correlation between these results and previously established Friedlander injury prediction curves. The velocity of complex blast waves was nearly the same as that of Friedlander waves for a given degree of injury: 3-4.5 meters/second for threshold injury, 8-12 meters/second for an LD1, and 12-17 meters/second for an LD50.

Animals↗
PubMed1989

CCK- and VIP-induced glycoprotein secretion from mouse gallbladder epithelium following vagotomy: a quantitative electron microscopic study.

The glycoprotein secretion from the mouse gallbladder epithelium induced by vasoactive intestinal peptide (VIP) and cholecystokinin (CCK) was investigated by electron microscopic morphometry. Both VIP and CCK caused a decrease in the volume density of the glycoprotein-containing granules of the principal cells. The effect on the gallbladder epithelium of a left-sided vagotomy was examined. Three and six weeks postvagotomy, slight decreases in cell and nuclear profile area and secretory granule volume density were noted. CCK induced a secretion of glycoprotein granules, whereas no such secretory effect due to VIP could be detected in animals 3 and 6 weeks after vagotomy. The results demonstrate that VIP, like CCK, is involved in glycoprotein secretion from the mouse gallbladder epithelium, but the secretory effect of VIP would appear to be dependent on an intact vagal innervation. The results are of interest in relation to the hypothesis that glycoprotein release may be a precipitating factor in the production of gallstones.

Animals↗
PubMed1987

Isoprenoid biosynthesis in multiple sclerosis, II. A possible role of NADPH.

Genetic predisposition in MS, influence of fat consumption on the disease, and excretion of lipid metabolites in urine led us to investigate isoprenoid metabolism in this disease. Ubiquinone concentration and biosynthesis was normal in lymphocytes. Cytochrome oxidase, which contains an isoprenoid side chain, was normal in activity. Cholesterol biosynthesis from acetate was found to be elevated in MS, and so was triglyceride biosynthesis. Increased biosynthesis may offer a very simple explanation to all the metabolites excreted (3-methylglutaconic acid, 2-hydroxy-2-methyl-3-butenoic acid and adipic acid). Increased biosynthesis may be caused by an elevated NADPH/NADP ratio, since such an elevation may also account for many other biochemical anomalies in MS. Elevated NADPH/NADP ratio may be of direct importance in the pathogenesis.

Cholesterol↗
PubMed1985

Isoprenoid biosynthesis in multiple sclerosis.

Recently discovered metabolites in urine have suggested a defect of isoprenoid metabolism in multiple sclerosis. Lymphocyte HMG-CoA reductase was found unaffected however, and so was lymphocyte biosynthesis of geraniol, farnesol and squalene from mevalonolactone. The level of dolichol in white matter of an MS brain was similar to that of a control sample. Serum ubiquinone, on the other hand, was decreased in multiple sclerosis. Ubiquinone in serum was both age-dependent and related to serum cholesterol. Active as well as stable MS displayed a decreased level of serum ubiquinone, and a reduced ubiquinone-cholesterol ratio. These results are compatible with a deficient ubiquinone biosynthesis in multiple sclerosis.

Adult↗
PubMed1985

Glycoprotein secretion from mouse gallbladder principal cells after chronic variation in parasympathetic activity. A morphometric study after vagotomy and cholinergic superstimulation.

Principal cells of mouse gallbladder epithelium were subjected to quantitative electron microscopic investigation either after superstimulation with pilocarpine for 12 days or 6 weeks after vagotomy at different levels. Cholinergic superstimulation caused a slight hypertrophy of the principal cells, whereas different types of vagotomy induced hypotrophic changes. In the superstimulated animals there was decreased sensitivity to single-dose stimulation with pilocarpine. In contrast, a supersensitivity was recorded in mice subjected to vagotomy. It is concluded that the parasympathetic nervous system is of importance for the regulation of glycoprotein secretion from mouse gallbladder principal cells. The demonstrated vagotomy-induced super-sensitivity may be responsible for an increased glycoprotein release, which in turn may be involved in the formation of gallstones occurring after truncal vagotomy in man.

Animals↗
PubMed1979

Effect of vagus nerve stimulation on the secretory-granule volume of the principal cells of the mouse gallbladder epithelium.

Experiments in mice were performed in order to investigate whether vagal activity could affect glycoprotein secretion from gallbladder principal cells. This cell type was studied with the electron microscope in control animals and after electric stimulation of the right or left nervus vagus. The volume density of glycoprotein containing granules was determined using morphometry. It was found that stimulation of the left vagus nerve significantly reduced the relative cellular volume of secretory granules in the principal cells of the gallbladder. Right vagus stimulation was accompanied by a weak but insignificant increase in secretory granule content. It is suggested that the left vagus nerve may exert a direct influence on glycoprotein secretion from gallbladder principal cells.

Animals↗
PubMed1979

Secretory behavior and ultrastructural changes in mouse gallbladder principal cells after stimulation with cholinergic and adrenergic drugs. A morphometric study.

Principal cells of mouse gallbladder epithelium were subjected to a quantitative electron microscope study after in vivo and in vitro exposure to pilocarpine, noradrenaline, atropine, and phenoxybenzamine. Stereologic measurements were performed on randomly selected principal cells, and special interest was paid to changes in the size of the secretory granule population of the cells. Thirty minutes after in vivo and in vitro stimulation with pilocarpine, there was a significant decrease of the volume density of the glycoprotein-containing granules in the principal cells. Thirty minutes after in vivo administration of the cholinergic antagonist atropine, a significant increase of this parameter was observed. In vitro incubation for 30 min with a combination of pilocarpine and atropine extinguished the pilocarpine-induced effect on the secretory granules. Noradrenaline and phenoxybenzamine (an alpha-adrenergic blocking agent) in vivo and in vitro (30 min) had no effect on the volume density of the secretory granules. The authors' findings suggest that principal cells of the mouse gallbladder epithelium exhibit an increased rate of secretion of glycoprotein granules after stimulation in vivo and in vitro with cholinergic agents, whereas adrenergic agents are without effect.

Animals↗
PubMed1977

Light and electron microscopic observations of the autonomic innervation of the mouse gallbladder mucosa. A histochemical, cytochemical, and secretory study.

The autonomic innervation of the mouse gallbladder mucosa was studied using histo- and cytochemical methods. In a light microscopic investigation the distribution of acetylcholinesterase (AChE) activity and formaldehyde-induced fluorescence was studied histochemically. Nerve fibres and small varicosities showed concentrations of AChE activity very close to the epithelium in the subepithelial connective tissue. No adrenergic nerves were observed in the mucosa. When using the electron microscope and employing the potassium permanganate fixation/staining technique only one sort of axonal enlargement was encountered, viz. the cholinergic type. These varicosities contained numerous agranular vesicles (500-600 A in diameter). No varicosities of the adrenergic (dense-cored vesicles) type were observed. Signs of increased secretory activity in the epithelium were observed in the first few minutes after cholinergic stimulation. After repeated in vivo stimulation, there was an almost total depletion of glycoprotein granules, best seen when using the cytochemical PA-CrA-silver technique. The findings suggest that the subepithelial connective tissue and the epithelium of the mouse gallbladder mucosa have a cholinergic innervation.

Acetylcholinesterase↗