Mode-coupling analysis of atomic dynamics in liquid lead.
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Journal Article↗
Biomedical subjects
K Larsson
Publications and source records attributed to K Larsson.
The risk of hip fractures in patients with primary hyperparathyroidism: a population-based cohort study with a follow-up of 19 years.
OBJECTIVE: To evaluate primary hyperparathyroidism (HPT) as a risk factor for hip fractures. DESIGN: A population-based, record-linked, prospective study with a mean observation time of 17 years (women) and 16.5 years (men). SETTING: A cohort obtained from a register of hospital admissions in the Uppsala Health Care Region, Sweden, 1965-1983. PARTICIPANTS: All patients (1373 women and 551 men) who were admitted to hospital with the diagnosis of HPT during the period. Comparisons were made with the entire background population. MEASUREMENTS: Cohort subjects were followed with regard to a first instance of hip fracture prior to or after the diagnosis of HPT. The observed number of cases was compared with that expected on the basis of person-years of observation and incidence rates in the background population. Analyses were made for cervical and trochanteric fractures, and for patients operated and not operated for HPT. MAIN RESULTS: (i) Women. During 23,341 person-years of observation, 67 cases of first hip fractures occurred, yielding a relative risk (RR) of 0.93 (95% confidence interval [CI] 0.72-1.19). The RR for cervical fractures was 0.77 (CI 0.54-1.06), and for trochanteric fractures 1.33 (CI 0.88-1.93). Operation for HPT did not influence the risk of hip fracture. (ii) Men. The total person-years was 9091. Eleven fractures were observed--compared with the expected 7.90 (RR 1.39; CI 0.69-2.50). Men operated for HPT had an increased risk for cervical hip fractures (RR 2.73; CI 1.18-5.39). Owing to the few fractures in this group (n = 8) the relevance of this is uncertain. CONCLUSIONS: This study indicates that HPT is not a risk factor for hip fractures in women.
Aged↗
A gene encoding sn-glycerol 3-phosphate dehydrogenase (NAD+) complements an osmosensitive mutant of Saccharomyces cerevisiae.
Osmoregulatory mutants of Saccharomyces cerevisiae with a defect in their capacity to readjust the cell volume/buoyant density after osmotically induced dehydration were enriched by density gradient centrifugation. Colonies derived from cells that remained dense after dehydration were screened for sensitivity to high concentrations of NaCl and defects in their osmotically induced production and intracellular accumulation of glycerol. The isolated osg (osmosensitive glycerol defective) mutants were recessive in heterozygous diploids and fell into four complementation groups (osg1-osg4). The osg1-1 mutant, described in this work, is unable to grow at low water potential and shows a decreased capacity for glycerol production and a strongly reduced activity of NAD(+)-dependent sn-glycerol 3-phosphate dehydrogenase (GPD), an enzyme in the glycerol-producing pathway. Complementation of the osg1-1 salt sensitivity defect with a low copy yeast genomic library led to the cloning of GPD1, encoding an S. cerevisiae GPD consisting of 391 amino acids and sharing 47-50% identity with GPD from other sources. Micro-sequencing of the N-terminus of purified S. cerevisiae GPD revealed a 20-amino-acid sequence that was identical to a nucleotide-deduced amino acid sequence in GPD1, but indicated that the enzyme is produced with an N-terminal extension that is removed from the functional enzyme. Subcellular fractionation does not indicate, however, that the putative pre-sequence targets GPD to any organelle; the enzyme appears to be located in the cytoplasm. Chromoblot and tetrad analysis were used to position the GPD1 gene to chromosome IV, with a distance of about 18 cM from trp1.
Amino Acid Sequence↗
Energy flux and osmoregulation of Saccharomyces cerevisiae grown in chemostats under NaCl stress.
The energetics and accumulation of solutes in Saccharomyces cerevisiae were investigated for cells grown aerobically in a chemostat under NaCl stress and glucose limitation. Changed energy requirements in relation to external salinity were examined by energy balance determinations performed by substrate and product analyses, with the latter including heat measurements by microcalorimetry. In both 0 and 0.9 M NaCl cultures, the catabolism was entirely respiratory at the lowest dilution rates tested but shifted to a mixed respiratory-fermentative metabolism at higher dilution rates. This shift occurred at a considerably lower dilution rate for salt-grown cells. The intracellular solute concentrations, as calculated on the basis of intracellular soluble space determinations, showed that the internal Na+ concentration increased from about 0.02 molal in basal medium to about 0.18 molal in 0.9 M NaCl medium, while intracellular K+ was maintained around 0.29 molal despite the variation in external salinity. The intracellular glycerol concentration increased from below 0.05 molal at low salinity to about 1.2 molal at 0.9 M NaCl. The concentrations of the internal solutes, however, changed insignificantly with growth rate and energy metabolism. The additional maintenance energy expenditure for growth at 0.9 M NaCl was, depending on the growth rate, 14 to 31% of the total energy requirement for growth at 0 M NaCl. Including the energy conserved in glycerol, the total additional energy demand for growth at 0.9 M NaCl corresponded to 28 to 51% of the energy required for growth at 0 M NaCl.
Adenosine Triphosphate↗
Gastroprotective capability of exogenous phosphatidylcholine in experimentally induced chronic gastric ulcers in rats.
Phosphatidylcholine (PC) is a main component of the hydrophobic gastric mucosal barrier. Exogenously administered, it prevents acute lesions. We evaluated the gastroprotective capacity of exogenous PC in both acute (ethanol- and indomethacin-induced) and chronic (indomethacin-induced) lesions in rats. Polyunsaturated (PPC) or hydrogenated PC in different concentrations were given intragastrically, before or after the injury factor, in single or repeated doses. Mucosal lesions were significantly reduced by a single dose of PPC, given before or after the injury factor, in both acute models. In the chronic model a single dose of PPC or hydrogenated PC significantly reduced lesions evaluated 6 h after ulcer induction, whereas after 72 h no protective effect was noticed. Repeated doses of PC were ineffective. In conclusion, in acute models exogenous PC reduces lesions in a dose-dependent manner and contributes to the mucosal defense. In chronic models an incomplete and temporary protection might be due to complex pathogenesis that requires activation of all levels in the mucosal defense. Strengthening of only one level was insufficient to restrict injury.
Animals↗
Green banana protection of gastric mucosa against experimentally induced injuries in rats. A multicomponent mechanism?
The protective capacities of fresh green (unripe) sweet bananas and of phosphatidylcholine and pectin (banana ingredients) against acute (ethanol- or indomethacin-induced) and chronic (indomethacin-induced) gastric mucosal lesions were evaluated in rats. Banana pulp was mixed with saline and given by gavage, as a pretreatment in a single dose. The identical protocol was used for pectin and phosphatidylcholine solution, and the dosages were adjusted to equal the amount of ingredients in the banana mixture, but higher concentrations were also given. The banana suspension reduced acute lesions, as did pectin and phosphatidylcholine in higher concentrations, but in concentrations as in fresh fruit no protective effects were observed except by pectin against indomethacin injury. In the model of chronic ulcers the banana suspension provided an incomplete and temporary protective effect. We conclude that the protective capacity of fresh green sweet bananas cannot be confined to only one active component. Pectin and phosphatidylcholine may protect gastric mucosa by strengthening the mucous-phospholipid layer, but the mechanism of protection afforded by bananas has to be further elucidated.
Acute Disease↗
Biochemical markers of bone metabolism in patients with fracture of the distal forearm.
Biomarkers for bone turnover have established a place in the investigation and follow-up examinations of patients with osteoporosis, but has received little attention for the possibility that the fracture itself might interfere with the interpretation of the results. In this investigation of patients with fracture of the distal forearm, biomarkers for bone formation (serum osteocalcin and alkaline phosphatases) and for resorption (urinary calcium and hydroxyproline) were determined together with serum calcium and parathyroid hormone (PTH) in longitudinal and cross-sectional studies. During 16 weeks of follow-up examinations, starting on the day of the fracture, 13 patients with Colles' fracture displayed a consistent pattern with a moderate increase in serum alkaline phosphatase and osteocalcin, whereas the indices of bone resorption appeared unaffected. There was also a significant increase in the serum calcium concentration and a reciprocal decrease in serum PTH. A cross-sectional comparison between 99 patients and controls showed elevated osteocalcin levels in the patients and an inverse relationship between these levels and bone mineral density. The findings demonstrate that fracture healing should be considered in the interpretation of biomarkers in osteoporotic patients, and that among patients with a fracture of the distal forearm, those with biochemical evidence of increased bone turnover have the lowest bone mass.
Aged↗
Acute exposure to swine dust causes bronchial hyperresponsiveness in healthy subjects.
Six urban subjects, with little or no previous experience of farm-work, were exposed to dust while weighing swine for 2-5 h. Three subjects experienced toxic symptoms 4-5 h after the beginning of exposure. Bronchial responsiveness increased in all subjects within 6 h (more than three doubling steps difference in a methacholine test). One week later, airway responsiveness had partly normalized. The mean (interquartile range) cumulative dose of methacholine causing a 20% decrease in forced expiratory volume in one second (FEV1) was 3.1 (1.0-6.6) mg, before exposure, fell to 0.13 (0.01-0.76) mg 6 h after exposure (p < 0.02), and was 0.99 (0.42-1.5) mg one week later (n = 5, p < 0.05), Mean (SD) FEV1 decreased 5 (2)%. The concentration of total dust varied between 9 and 14 mg.m-3 and of endotoxin between 0.1 and 0.5 mu g.m-3. Thus inhalation of swine farm dust, caused a marked increase in bronchial responsiveness in non-sensitized subjects.
Adult↗
The selective 5-HT2 receptor antagonist amperozide attenuates 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-induced inhibition of male rat sexual behavior.
This study was aimed at exploring the role of 5-HT2/5-HT1C neurotransmission in male rat sexual behavior. The administration of the 5-HT2/5-HT1C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (1 mg/kg), suppressed sexual activity in most of the animals. The suppressive effect of DOI was antagonized by treatment with amperozide, a selective 5-HT2 receptor antagonist, in doses which did not by themselves affect sexual activity. In addition, several other serotonin antagonists were tested with varying affinity profiles for 5-HT2/5-HT1C receptors, including ketanserin, ritanserin, and mesulergine. All these compounds antagonized the suppressive action of DOI. In contrast, no antagonizing effect was obtained by treatment with (-)-alprenolol, a 5-HT1A antagonist. The present findings suggest that 5-HT2/5-HT1C receptors might be involved in the neural control of male rat sexual behavior, presumably by exerting an inhibitory influence on the behavior.
Alprenolol↗
Bronchodilator treatment in asthma: continuous or on demand?
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Asthma↗
Stimulation of 5-HT1A and 5-HT1B receptors in brain regions and its effects on male rat sexual behaviour.
In the present series of experiments we compared the effect of injecting serotonin (40 micrograms/cannula), the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (5.0 micrograms/cannula), and the 5-HT1B/C agonist, trifluoromethyl-phenyl-piperazine (TFMPP) (1.0 micrograms/cannula), into the preoptic area, the nucleus accumbens and the nucleus raphe dorsalis. The dose injected was selected on the basis of dose-response curves. Injection of serotonin and TFMPP into the medial preoptic area and nucleus accumbens resulted in an inhibition of male sexual behaviour, as evidenced by an increase in the number of mounts and a prolongation of the ejaculation latency. Injection of 8-OH-DPAT into these brain areas facilitated copulatory behaviour as evidenced by a reduction in the number of mounts, intromissions and ejaculation latency. Administration of these compounds into the nucleus raphe dorsalis produced no effect, except for a prolongation of the intromission latency after serotonin. These results would suggest that at least some of the 5-HT1A receptors involved in the facilitation of male sexual behaviour are located postsynaptically in limbic brain areas that regulate male sexual behaviour. On the basis of the similarities between the inhibitory effects of serotonin and TFMPP, the present results further support the idea that endogenous serotonin acts via the stimulation of 5-HT1B receptors to inhibit male sexual behaviour.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
The staggerer gene curtails the reproductive life span of females.
Three studies were undertaken to investigate some features of the reproductive activity of female staggerer mice of the C57BL/6 strain. It was found that in the staggerer female, (1) vaginal opening and onset of vaginal estrous cycling were delayed; (2) the vaginal estrous cycle was irregular and characterized by abnormally prolonged diestrous and estrous phases, and (3) the reproductive life span of the mutant female was confined to a 3-month period after puberty. The abnormalities observed in sexual functions suggest a specific influence of the staggerer gene on reproductive activity.
Animals↗
Screening for antibodies against gliadin in patients with osteoporosis.
Intestinal disease might contribute to osteopenia. Measurements of IgA antibodies to gliadin have been established as an accepted screening procedure for detection of coeliac disease. When we applied these measurements to 92 patients with verified osteoporosis, 11 subjects (12%) were found to have elevated levels. This is markedly higher than the incidence in healthy subjects (3%). However, the patients with raised levels of IgA antibodies displayed no clinical symptoms and no laboratory evidence of calcium malabsorption. Thus their values for serum calcium, phosphate, parathyroid hormone (PTH), alkaline phosphatase and osteocalcin, as well as the fasting urinary excretion of hydroxyproline and calcium, were similar to those found in other patients with osteoporosis. Intestinal biopsy verified coeliac disease in three patients and was normal in another three. This gives an incidence of verified coeliac disease in this patient group that is approximately tenfold higher than that in the healthy population. Subclinical coeliac disease appears to be unusually over-represented among patients with idiopathic osteoporosis, and screening for gliadin antibodies might therefore be a valuable addition to the routine assessment of the osteopenic patient. The mechanisms underlying the relationship are not clear, but calcium malabsorption is not evident.
Aged↗
Formulation of a drug delivery system based on a mixture of monoglycerides and triglycerides for use in the treatment of periodontal disease.
This paper describes the development of a stable, controlled-release formulation of metronidazole for use in the treatment of periodontal disease. It is formulated as a suspension, which undergoes transformation to a release-controlling, semi-solid on contact with gingival fluid. The system is based on the ability of mixtures of monoglycerides and triglycerides to form liquid crystals, i.e., reversed hexagonals, in contact with water. The reversed hexagonal form was found to have the most favourable sustained release properties, compared with those from the cubic form. The source of metronidazole is the prodrug, metronidazole benzoate, which further helps to slow down the release rate. Product characteristics are assessed by differential scanning calorimetry and viscometry. The release data derive from the results of in vitro dissolution tests. X-ray diffraction, phase diagrams, and polarized light microscopy were used to elucidate the structure of the liquid crystalline phases.
Biodegradation, Environmental↗
Effects of phosphatidylcholine and phosphatidylinositol on acetic-acid-induced colitis in the rat.
The therapeutic effects of exogenous phosphatidylcholine and phosphatidylinositol on acetic acid-induced colitis in rats were evaluated. A uniform colitis developed 4 days after instillation of 4% acetic acid for 15 s in an excluded colonic segment, also resulting in a 6-fold increase in mucosal permeability. Instillation of 12.5 mg phosphatidylcholine once daily from the day after acetic acid instillation and for the following 2 days prevented partially the development of colitis causing partial mucosal restoration. By increasing the phosphatidylcholine dose to 25 and 50 mg, a better preventive effect was achieved. By starting the phosphatidylcholine instillation immediately after the acetic acid exposure, almost complete prevention of the colitis could be obtained. Similarly, 50 mg phosphatidylinositol in each instillation with the first administration immediately after acetic acid administration resulted in complete prevention of the colitis and a significant decrease in mucosal permeability expressed as a plasma exudation into the colonic lumen. Similar results were obtained when phosphatidylcholine was administered immediately after acetic acid, but the drug then had to be applied twice daily. In contrast, a single application of the same total dose (150 mg) of the two different phospholipids, either 30 min before or immediately after acetic acid administration, could not prevent the development of colitis. It is concluded that both phosphatidylcholine and phosphatidylinositol have a therapeutic effect on the development of acetic acid-induced colitis in the rat.
Acetates↗
Hyaluronic acid (hyaluronan) in BAL fluid distinguishes farmers with allergic alveolitis from farmers with asymptomatic alveolitis.
Pulmonary function measurements, bronchoalveolar lavage (BAL), and analyses of precipitating antibodies in blood were performed in 12 farmers wtih no symptoms from the airways and 12 farmers who were admitted to the hospital due to acute symptoms of alveolitis (all nonsmokers). In addition, a bronchial methacholine provocation test was performed in the asymptomatic farmers. In 11 of the 12 symptomatic farmers but in none of the asymptomatic farmers, precipitating antibodies against one or more of the microorganisms which usually occur in a farmer's environment were found. In the farmers with symptomatic alveolitis, a restrictive impairment of pulmonary function was found, while pulmonary function was normal in all asymptomatic farmers. Findings in the BAL fluid showed increased concentrations of total cells, lymphocytes, and neutrophils and elevated levels of albumin, fibronectin, and angiotensin-converting enzyme in asymptomatic farmers compared with our own reference group. The same analyses in BAL fluid from the symptomatic farmers revealed a further increase in all parameters compared with the asymptomatic farmers. The BAL fluid from asymptomatic farmers had normal levels of hyaluronic acid (hyaluronan) and procollagen 3 N-terminal peptide, while these levels were significantly increased in the symptomatic group. We conclude that inflammation in the alveolar space and signs of activation of alveolar macrophages are present in farmers regardless of respiratory symptoms, although these findings are more pronounced in the presence of symptoms of acute alveolitis; however, the findings of impaired pulmonary function and the occurrence of precipitins and elevated levels of hyaluronic acid and procollagen 3 N-terminal peptide in BAL fluid were exclusively found in the farmers with airways symptoms. We postulate the hyaluronic acid, due to its pronounced ability to immobilize water, may be of importance in the development of the pulmonary function impairment observed in farmer's lung disease.
Acute Disease↗
Alterations in bronchoalveolar lavage fluid but not in lung function and bronchial responsiveness in swine confinement workers.
Testing of lung function and bronchial reactivity, bronchoalveolar lavage (BAL), and a skin prick test with a standard panel and six "swine" extracts obtained from swine and swine environment were performed in 20 randomly selected nonsmoking swine confinement workers. In addition, blood samples for detection of antibodies by the diffusion in gel-enzyme-linked immunosorbent assay (DIG-ELISA) technique and precipitating antibodies were drawn. Air samples for measurement of dust and endotoxin levels were collected. All the farmers regarded themselves as healthy. The results were compared with reference groups consisting of urban nonsmoking subjects who had not been exposed to pig farming environment. The pig farmers had normal lung function and the bronchial reactivity was not different from the reference group. In the BAL fluid of the farmers, the concentration of total cells and granulocytes was increased while the concentrations of lymphocytes and macrophages were normal. The BAL fluid concentrations of albumin, fibronectin, and hyaluronan were elevated in the farmers. Skin prick tests with swine extracts were negative in all farmers. Antibodies (assessed by DIG-ELISA) against swine dander, swine dust, and pig feed were increased and precipitating antibodies against swine dander were found in 14, against pig food in five, and against swine confinement dust in three of the 20 pig farmers. The concentration of airborne total dust was 7.4 mg/cu mm and the endotoxin concentration was 37 (22 to 60) ng/cu mm during tending the pigs and increased, during feeding, to 13.8 mg/cu mm and 315 (194 to 716) ng/cu mm, respectively. There was no correlation between exposure and lung function or lavage findings. In conclusion, randomly selected pig farmers had signs of airway inflammatory reaction and activation of the immune system without alteration in lung function and bronchial reactivity.
Adult↗
Influence of beta-adrenergic receptor function during terbutaline treatment on allergen sensitivity and bronchodilator response to terbutaline in asthmatic subjects.
Nine asthmatic patients with an allergy to birch or timothy underwent bronchial allergen provocations on three different trial days, with intervals of 2 to 5 wk. Two weeks prior to one of the provocations, no medication was allowed. Before the other two provocations the patients had been on continuous treatment with oral terbutaline (7.5-mg slow-release pill bid) for 2 wk, which was discontinued 12 or 48 h before the allergen provocation. After allergen challenges, terbutaline was inhaled in increasing doses (0.5 mg, 1.0 mg, and 2.0 mg), and pulmonary function was measured after each dose. Before each allergen provocation, blood samples were drawn for measurements of catecholamine and terbutaline concentrations and for in vitro measurements of beta-adrenergic receptor function on lymphocytes (isoproterenol-induced accumulation of cyclic AMP). Beta-adrenergic receptor function on blood lymphocytes was impaired after the two treatment periods, compared with the drug-free period, and was significantly more depressed at 12 h than 48 h after dosing. The bronchial responsiveness to allergen, defined as PC20PEF (median values), was 1,700 biologic units (BU) after the period of no treatment and 220 BU and 445 BU at 12 and 48 h after discontinuation of the terbutaline treatment (p less than 0.1 after 48 h). Five of the nine patients exhibited increased bronchial responsiveness 48 h after treatment, compared to results without treatment. The responsiveness was similar on all occasions in three patients. The bronchodilator response to inhaled terbutaline after allergen-induced bronchoconstriction was attenuated (p less than 0.01) at both 12 and 48 h after terbutaline, compared to results without treatment, indicating desensitization also of the bronchial beta-adrenergic receptors. We conclude that the early bronchial responsiveness to allergen is increased following a period of continuous treatment with a beta-adrenergic receptor agonist in some asthmatic patients and that the capability of a beta-agonist to reverse allergen-induced bronchoconstriction is attenuated after beta-agonist treatment.
Adult↗