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Biomedical subjects

A Lindqvist

Publications and source records attributed to A Lindqvist.

At least 19 recordsLinked to original sources
PubMed2006

Once-daily dosing with budesonide/formoterol compared with twice-daily budesonide/formoterol and once-daily budesonide in adults with mild to moderate asthma.

Adherence to maintenance therapy is often poor in patients with asthma. Simplifying dosing regimens has the potential to improve both adherence and asthma-related morbidity. In this 12-week, randomized, double-blind, double-dummy, parallel-group study, 617 patients with mild to moderate persistent asthma (mean forced expiratory volume in 1s [FEV1] 78.5% predicted) who were not optimally controlled on inhaled corticosteroids (200-500 microg/day) were randomized to once-daily budesonide/formoterol (80/4.5 microg, 2 inhalations in the evening), twice-daily budesonide/formoterol (80/4.5 microg, 1 inhalation), or a corresponding dose of budesonide once-daily (200 microg, 1 inhalation in the evening). All patients received budesonide (100 microg twice daily) during a 2-week run-in. Changes in mean morning peak expiratory flow (PEF) were similar for od budesonide/formoterol (23.4 l/min) and twice-daily budesonide/formoterol (24.1 l/min), and both were greater than with budesonide (5.5 l/min; both P<0.001). Evening PEF, symptom-free days, reliever-free days, and asthma control days were improved with budesonide/formoterol therapy vs. budesonide (P<0.05 vs. budesonide for all variables). All treatments were well tolerated. Budesonide/formoterol administered once daily in the evening is a convenient treatment regimen that is as effective in improving asthma control as twice-daily dosing in patients with mild to moderate persistent asthma.

Administration, Inhalation↗
PubMed2006

High-fat diet impairs hippocampal neurogenesis in male rats.

High fat diets and obesity pose serious health problems, such as type II diabetes and cardiovascular disease. Impaired cognitive function is also associated with high fat intake. In this study, we show that just 4 weeks of feeding a diet rich in fat ad libitum decreased hippocampal neurogenesis in male, but not female, rats. There was no obesity, but male rats fed a diet rich in fat exhibited elevated serum corticosterone levels compared with those fed standard rat chow. These data indicate that high dietary fat intake can disrupt hippocampal neurogenesis, probably through an increase in serum corticosterone levels, and that males are more susceptible than females.

Animals↗
PubMed2005

Ghrelin treatment reverses the reduction in weight gain and body fat in gastrectomised mice.

BACKGROUND AND AIMS: The gastric hormone ghrelin has been reported to stimulate food intake, increase weight gain, and cause obesity but its precise physiological role remains unclear. We investigated the long term effects of gastrectomy evoked ghrelin deficiency and of daily ghrelin injections on daily food intake, body weight, fat mass, lean body mass, and bone mass in mice. METHODS: Ghrelin was given by subcutaneous injections (12 nmol/mouse once daily) for eight weeks to young female mice subjected to gastrectomy or sham operation one week previously. RESULTS: Gastrectomy reduced plasma concentrations of total ghrelin (octanoylated and des-octanoylated) and active (octanoylated) ghrelin by approximately 80%. Immediately after injection of ghrelin, the plasma concentration was supraphysiological and was still elevated 16 hours later. Daily food intake was not affected by either gastrectomy or ghrelin treatment. The effect of ghrelin on meal initiation was not studied. At the end point of the study, mean body weight was 15% lower in gastrectomised mice than in sham operated mice (p<0.001); daily ghrelin injections for eight weeks partially prevented this weight loss. In sham operated mice, ghrelin had no effect on body weight. The weight of fat was reduced in gastrectomised mice (-30%; p<0.01). This effect was reversed by ghrelin, enhancing the weight of fat in sham operated mice also (+20%; p<0.05). Gastrectomy reduced lean body mass (-10%; p<0.01) and bone mass (-20%; p<0.001) compared with sham operated mice. Ghrelin replacement prevented the gastrectomy induced decrease in lean body mass but did not affect bone. In sham operated mice, ghrelin affected neither of these two parameters. CONCLUSIONS: Ghrelin replacement partially reversed the gastrectomy induced reduction in body weight, lean body mass, and body fat but not in bone mass. In sham operated mice, ghrelin only increased fat mass. Our results suggest that ghrelin is mainly concerned with the control of fat metabolism and that ghrelin replacement therapy may alleviate the weight loss associated with gastrectomy.

Adipose Tissue↗
PubMed2004

Histamine and histidine decarboxylase are hallmark features of ECL cells but not G cells in rat stomach.

The oxyntic mucosa of the rat stomach is rich in ECL cells which produce and secrete histamine in response to gastrin. Histamine and the histamine-forming enzyme histidine decarboxylase (HDC) have been claimed to occur also in the gastrin-secreting G cells in the antrum. In the present study, we used a panel of five HDC antisera and one histamine antiserum to investigate whether histamine and HDC are exclusive to the ECL cells. By immunocytochemistry, we could show that the ECL cells were stained with the histamine antiserum and all five HDC antisera. The G cells, however, were not stained with the histamine antiserum, but with three of the five HDC antisera. Thus, histamine and HDC coexist in the ECL cells (oxyntic mucosa) but not in G cells (antral mucosa). Western blot analysis revealed a typical pattern of HDC-immunoreactive bands (74, 63 and 54 kDa) in oxyntic mucosa extracts with all five antisera. In antral extracts, immunoreactive bands were detected with three of the five HDC antisera (same as above); the pattern of immunoreactivity differed from that in oxyntic mucosa. Food intake of fasted rats or treatment with the proton pump inhibitor omeprazole raised the HDC activity and the HDC protein content of the oxyntic mucosa but not of the antral mucosa; the HDC activity in the antrum was barely detectable. We suggest that the HDC-like immunoreactivity in the antrum represents a cross-reaction with non-HDC proteins and conclude that histamine and HDC are hallmark features of ECL cells but not of G cells.

Animals↗
PubMed2003

Airway inflammation and basement membrane tenascin in newly diagnosed atopic and nonatopic asthma.

Previous studies have shown both similar and distinct inflammatory changes in atopic and nonatopic asthma. This study was set to investigate the bronchial inflammatory cell infiltrate and subepithelial basement membrane (BM) tenascin deposition in subjects with newly diagnosed asthma and bronchial hyperresponsiveness (BHR). Seventy-nine asthmatic subjects (age 18-60 years) were recruited and 58 were atopic according to skin prick testing. The patients recorded asthma symptoms and peak flow measurements for 14 days. Lung function and BHR were measured by spirometry and histamine challenge. Serum eosinophil cationic protein (ECP) and blood eosinophils were assessed. Fiberoptic bronchoscopy was performed to obtain bronchial biopsies. Serum ECP was higher in the atopic group but eosinophil counts did not differ. There were no differences in inflammatory cells studied (activated eosinophils, T-lymphocytes, mast cells or macrophages) between nonatopic and atopic subjects. BM tenascin layer was significantly thicker in atopic compared with nonatopic subjects (7.6 vs 6.3 microm, P = 0.007). The thickness of tenascin correlated with eosinophil, T-lymphocyte, and macrophage counts, as well as with IL-4-positive cell counts and the correlation was seen only in atopic asthmatics. These findings suggest that inflammatory cells may have a regulatory role in tenascin expression in atopic asthma.

Adult↗
PubMed2003

Sustained reduction in bronchial hyperresponsiveness with inhaled fluticasone propionate within three days in mild asthma: time course after onset and cessation of treatment.

BACKGROUND: Bronchial hyperresponsiveness (BHR) is characteristic of asthmatic airways, is induced by airway inflammation, and is reduced by inhaled corticosteroids (ICS). The time course for the onset and cessation of the effect of ICS on BHR is unclear. The effect of inhaled fluticasone propionate (FP) on BHR in patients with mild persistent asthma was assessed using time intervals of hours, days and weeks. METHODS: Twenty six asthmatic patients aged 21-59 years were selected for this randomised, double blind, parallel group study. The effect of 250 micro g inhaled FP (MDI) administered twice daily was compared with that of placebo on BHR assessed using a dosimetric histamine challenge method. The dose of histamine inducing a decrease in forced expiratory volume in 1 second (FEV(1)) by 15% (PD(15)FEV(1)) was measured before and 6, 12, 24 and 72 hours, and 2, 4 and 6 weeks after starting treatment, and 48 hours, 1 week and 2 weeks after cessation of treatment. Doubling doses of changes in PD(15)FEV(1) were calculated and area under the curve (AUC) statistics were used to summarise the information from individual response curves. RESULTS: The increase in PD(15)FEV(1) from baseline was greater in the FP group than in the placebo group; the difference achieved significance within 72 hours and remained significant until the end of treatment. In the FP group PD(15)FEV(1) was 1.85-2.07 doubling doses above baseline between 72 hours and 6 weeks after starting treatment. BHR increased significantly within 2 weeks after cessation of FP treatment. CONCLUSIONS: A sustained reduction in BHR to histamine in patients with mild asthma was achieved within 3 days of starting treatment with FP at a daily dose of 500 micro g. The effect tapered within 2 weeks of cessation of treatment.

Administration, Inhalation↗
PubMed2003

The role of the novel D2/beta2-agonist, Viozan (sibenadet HCl), in the treatment of symptoms of chronic obstructive pulmonary disease: results of a large-scale clinical investigation.

Viozan (sibenadet HCl, AR-C68397AA) is a novel dual D2 dopamine receptor, beta2-adrenoceptor agonist, developed specifically to treat the key symptoms of chronic obstructive pulmonary disease (COPD), breathlessness, cough and sputum. The dual sensory nerve modulation and bronchodilator effects of sibenadet have been demonstrated in initial dose-ranging studies of patients with COPD and large-scale clinical evaluation has now been completed. Sibenadet efficacy was determined by assessing symptomatic changes, as defined by the novel assessment tool, the Breathlessness, Cough and Sputum Scale (BCSS). The findings of two placebo-controlled studies are reported. These multicentre, double-blind, placebo-controlled studies recruited over 2000 patients with stable COPD, randomized to receive sibenadet (500 microg) or placebo, pressurized metered-dose inhaler (pMDI) (three times daily) for a period of 12 or 26 weeks. Diary cards were completed daily by patients throughout the study to record BCSS scores, peak expiratory flow (PEF), study drug and rescue bronchodilator usage, changes in concomitant medication and adverse events. The primary endpoints were defined as change from baseline to the final 4 weeks of the treatment period in mean BCSS total score, and forced expiratory volume in one second (FEV1) measured 1 hour after administration of the final dose of study drug and expressed as a percentage of the predicted FEV1. In addition, clinic assessments were made to determine changes in pulmonary function, health-related quality of life, perception of treatment efficacy and adverse events. Despite initial improvements in mean daily BCSS total scores in patients receiving sibenadet, the difference in the change from baseline to the final 4 weeks of the treatment period between the two treatment groups was neither statistically significant, nor considered to be of clinical importance. Although marked bronchodilator activity was seen early on with sibenadet treatment, the duration of effect diminished as the studies progressed. Sibenadet use was not associated with any safety concerns. These studies, utilizing the novel BCSS, have clearly illustrated that, despite initial symptomatic improvement with sibenadet therapy, this clinical benefit was not sustained over the course of the study.

Administration, Inhalation↗
PubMed2002

Investigative bronchoscopy and endobronchial biopsy is well tolerated in hyperreactive asthma patients.

The tolerability of 57 non-smoking asthma patients inhaling salbutamol as needed (ATS, 18--60 years, 60% < or = FEV1 < or =100%, PD15FEV1 <0.4 mg histamine) to fibreoptic bronchoscopy (FOB) and endobronchial biopsy was studied. The FOB was done in local Lignocaine anaesthesia, and from five to eight biopsy specimens were taken from the bronchial mucosa of the right lung. The tolerability was measured as cough/bronchospasm during the procedure (from 0 = normal to 3 = interrupted procedure), success of the procedure, and untoward occurrences. Twenty-seven of the 57 patients (48%) had no cough or bronchospasm during the FOB (score 0). Few coughs of no importance (score 1) were documented in 23 patients (40%). Seven patients (12%) had cough and/or bronchospasm interfering with the FOB procedure (score 2). The FOB procedure was not interrupted because of cough and/or bronchospasm (score 3) in any patient. Scores of cough and/or bronchospasm diminished progressively with the increase of PD15FEV1 histamine. The success of the procedure was 100%. Two patients had untoward medical occurrences requiring additional rescue medication (3.5%). In conclusion, we found that hyperreactivity predicts cough and/or bronchospasm during the FOB. Cough and/or bronchospasm are frequently observed during the bronchial procedure, but they are mild and of minor clinical importance. An investigational endobronchial procedure can be successfully performed in mildly or moderately obstructive asthmatic patients, even in cases with severe bronchial hyperreactivity.

Adolescent↗
PubMed2001

Smooth muscle cell response to mechanical injury involves intracellular calcium release and ERK1/ERK2 phosphorylation.

We have investigated possible signaling pathways coupled to injury-induced ERK1/2 activation and the subsequent initiation of vascular rat smooth muscle cell migration and proliferation. Aortic smooth muscle cells were cultured to confluency and subjected to in vitro injury under serum-free conditions. In fluo-4-loaded cells, injury induced a rapid wave of intracellular Ca(2+) release that propagated about 200 microm in radius from the injured zone, reached a peak in about 20 s, and subsided to the baseline within 2 min. The wave was abolished by prior treatment with the sarcoplasmic reticulum ATPase inhibitor thapsigargin, but not by omission of extracellular Ca(2+). ERK1/2 activation reached a peak at 10 min after injury and was inhibited by the MEK1 inhibitor PD98059, as well as by thapsigargin, fluphenazine, genistein, and the Src inhibitor PP2. These inhibitors also reduced [(3)H]thymidine incorporation and migration of cells into the injured area determined at 48 h after injury. These results show that mechanical injury to vascular smooth muscle cells induces a Ca(2+) wave which is dependent on intracellular Ca(2+) release. Furthermore, the injury activates ERK1/2 phosphorylation as well as cell migration and replication.

Animals↗
PubMed2001

Platelet-derived growth factor receptors expressed in response to injury of differentiated vascular smooth muscle in vitro: effects on Ca2+ and growth signals.

Vascular smooth muscle cells (VSMCs) in the intact vascular wall are differentiated for contraction, whereas the response to vascular injury involves transition towards a synthetic phenotype, with increased tendency for proliferation. Platelet-derived growth factor (PDGF) is thought to be important for this process. We investigated expression and functional coupling of PDGF receptors (PDGFRs) alpha and beta in rat tail arterial rings kept in organ culture, in order to capture early events in the phenotypic transition. In freshly dissected rings no PDGFR immunoreactivity was found in medial VSMCs, whereas PDGFR alpha was detected in nerve fibres. After organ culture for 1-4 days PDGFR alpha and beta as well as phospholipase Cgamma2 (PLCgamma2), known to couple to PDGFR, were expressed in VSMCs within 100 microm of the cut ends. Calponin, a marker for the contractile phenotype, was decreased near the injured area, suggesting that cells were in transition towards synthetic phenotype. In these cells, which showed functional Ca2+-release from the sarcoplasmic reticulum, PDGF-AB (100 ng x mL(-1)) had no effect on [Ca2+]i, whereas cultured VSMCs obtained from explants of rat tail arterial rings responded to PDGF-AB with an increase in [Ca2+]i. However, PDGFR within the cultured rings coupled to growth signalling pathways, as PDGF-AB caused a tyrphostin AG1295-sensitive activation of extracellular signal-regulated kinases 1 and 2 and of [3H]-thymidine incorporation. Thus, early expression of PDGFR in VSMC adjacent to sites of vascular injury coincides with signs of dedifferentiation. These receptors couple to growth signalling, but do not activate intracellular Ca2+ release.

Animals↗
PubMed2001

Distribution of the Escherichia coli structural maintenance of chromosomes (SMC)-like protein MukB in the cell.

Fluorescent polyclonal antibodies specific for MukB have been used to study its localization in Escherichia coli. In wild-type cells, the MukB protein appeared as a limited number of oblong shapes embracing the nucleoid. MukB remained associated with the nucleoid in the absence of DNA replication. The centre of gravity of the dispersed MukB signal initially localized near mid-cell, but moved to approximately quarter positions well before the termination of DNA replication and its subsequent reinitiation. Because MukB had been reported to bind to FtsZ and to its eukaryotic homologue tubulin in vitro, cells were co-labelled with MukB- and FtsZ-specific fluorophores. No co-localization of MukB with polymerized FtsZ (the FtsZ ring) was observed at any time during the cell cycle. A possible role for MukB in preventing premature FtsZ polymerization and in DNA folding that might assist DNA segregation is discussed.

Antibodies↗
PubMed2001

The dynamics, prevalence and impact of nematode infections in organically raised sheep in Sweden.

A three-year survey (1997-99) was carried out on organically reared sheep flocks throughout Sweden. The aim was to determine the prevalence and intensity of nematode infections and to establish relationships between sheep management practices and parasite infections. Faecal samples from ewes and lambs were collected from 152 organic flocks around lambing-time and during the grazing-period for analysis. Results were compared with the different management practices that farmers use to prevent parasitism in their flocks. A high proportion of the flocks was infected with nematodes. The most prevalent species were Haemonchus contortus, Teladorsagia circumeincta, Trichostrongylus axei. T. colubriformis and Chabertia ovina and infections progressively increased during summer in lambs grazing on permanent pastures. Severity of parasitic infection in lambs was highly dependent on egg output from the ewes. H. contortus was found in 37% of the flocks, even at latitudes approximating the Polar Circle. Nematodirus battus was recorded for the first time in Sweden during the course of this study. Lambs turned out onto permanent pasture showed higher nematode faecal egg counts (epg) than lambs that had grazed on pastures, which had not carried sheep the previous year. This beneficial effect of lambs grazing non-infected pastures persisted if the ewes were treated with an anthelmintic before turn-out and if the lambs were kept on pastures of low infectivity after weaning. In lambs, the prevalence and the magnitude of their egg counts were higher during autumn in flocks where lambs were slaughtered after 8 months of age, compared with flocks where all lambs were slaughtered before this age. These results will be used in providing advice to farmers of ways to modify their flock management in order to minimise the use of anthelmintics, but at the same time efficiently produce prime lambs.

Animals↗
PubMed2001

Substitution mutation C268Y causes 17 beta-hydroxysteroid dehydrogenase 3 deficiency.

The 17 beta-hydroxysteroid dehydrogenase (HSD) type 3 isozyme catalyzes the conversion of androstenedione to testosterone in the testis. Deleterious mutations in the HSD17B3 gene cause undermasculinization in genetic males attributable to impaired testosterone biosynthesis. Hence, a hallmark of this autosomal recessive disorder is a decreased plasma testosterone-to-androstenedione ratio. Here, a novel C268Y substitution mutation in exon 10 of the HSD17B3 gene, in a subject with 17 beta-HSD 3 deficiency, is reported. Reconstitution experiments with recombinant protein reveal that substitution of tyrosine for cysteine at position 268 of 17 beta-HSD type 3 abrogates the enzymatic activity. This finding brings to 20 the number of mutations in the HSD17B3 gene that cause male undermasculinization.

17-Hydroxysteroid Dehydrogenases↗
PubMed2000

alpha(1)-Microglobulin: a yellow-brown lipocalin.

alpha(1)-Microglobulin, also called protein HC, is a lipocalin with immunosuppressive properties. The protein has been found in a number of vertebrate species including frogs and fish. This review summarizes the present knowledge of its structure, biosynthesis, tissue distribution and immunoregulatory properties. alpha(1)-Microglobulin has a yellow-brown color and is size and charge heterogeneous. This is caused by an array of small chromophore prosthetic groups, attached to amino acid residues at the entrance of the lipocalin pocket. A gene in the lipocalin cluster encodes alpha(1)-microglobulin together with a Kunitz-type proteinase inhibitor, bikunin. The gene is translated into the alpha(1)-microglobulin-bikunin precursor, which is subsequently cleaved and the two proteins secreted to the blood separately. alpha(1)-Microglobulin is found in blood and in connective tissue in most organs. It is most abundant at interfaces between the cells of the body and the environment, such as in lungs, intestine, kidneys and placenta. alpha(1)-Microglobulin inhibits immunological functions of white blood cells in vitro, and its distribution is consistent with an anti-inflammatory and protective role in vivo.

Alpha-Globulins↗
PubMed2000

Neuropeptide- and tyrosine hydroxylase-immunoreactive nerve fibers in painful Morton's neuromas.

We examined the expression of three neuropeptides that have been implicated in nociceptive transmission, and the sympathetic nerve fiber marker tyrosine hydroxylase, in 11 painful human Morton's neuromas, using immunohistochemistry. Antibodies against the neural markers RT97 and PGP 9.5 were used to map the general nerve fiber organization of the neuromas. Four specimens of normal human peripheral nerves were used as controls. Substance P, calcitonin gene-related peptide, and neuropeptide Y immunoreactivities were more pronounced in neuroma tissue than in control nerves. Neuropeptide immunofluorescence was seen both in larger nerve fiber trunks and in masses of disorganized axon profiles dispersed in loose connective tissue. Tyrosine hydroxylase immunoreactivity was present at varying levels of expression in neuroma nerve fiber trunks, in connective tissue nerve fiber bundles, and around some blood vessels. Our findings suggest that neuropeptides are involved in the response to injury in Morton's neuromas and that they could play a role in initiation or modulation of pain. In addition, pain from Morton's neuromas could be influenced by sympathetic nerve fibers.

Adult↗
PubMed2000

Anabolic androgenic steroids affects alcohol intake, defensive behaviors and brain opioid peptides in the rat.

The present study investigated whether a relationship exists between nandrolone decanoate and voluntary ethanol intake in laboratory rats. Animals were subjected to daily subcutaneous injections with nandrolone decanoate (15 mg/kg) during 2 weeks. One group of animals was tested for voluntary alcohol intake 1 week after the end of the 2-week treatment period and another group received alcohol 3 weeks after the treatment. In addition, assessment of defensive behaviors and immunoreactivity (ir) levels of the brain opioid peptides dynorphin B and Met-enkephalin-Arg-Phe (MEAP) were performed. The nandrolone decanoate-treated animals were significantly more aggressive and showed lower fleeing and freeezing reaction than the oil-treated controls. Treatment with nandrolone decanoate enhanced voluntary alcohol intake, regardless if it was presented 1 or 3 weeks after end of the treatment period. These animals had a decreased activity of dynorphin B-ir in the nucleus accumbens, decreased levels of MEAP-ir in the periaqueductal gray (PAG) and higher levels of MEAP-ir in the hypothalamus compared to controls. In line with previous studies, this suggests that the altered dynorphin B-ir activity may promote the rewarding effects of ethanol and thereby increasing alcohol intake, whereas MEAP-ir may be associated with the ability to control the aggressive reaction. Abuse of nandrolone decanoate may thus constitute a risk factor for increased alcohol consumption and defensive aggression. In human, this constellation of behavioral symptoms is closely related to acts of crimes and violence and is often observed among those abusing anabolic androgenic steroids.

Aggression↗
PubMed2000

Roles of respiratory oxidases in protecting Escherichia coli K12 from oxidative stress.

Isogenic strains of Escherichia coli that were defective in either of the two major aerobic terminal respiratory oxidases (cytochromes bo' and bd) or in the putative third oxidase (cytochrome bd-II) were studied to elucidate role(s) for oxidases in protecting cells from oxidative stress in the form of H2O2 and paraquat. Exponential phase cultures of all three oxidase mutants exhibited a greater decline in cell viability when exposed to H2O2 stress compared to the isogenic parent wild-type strain. Cytochrome bo' mutants showed the greatest sensitivity to H2O2 under all conditions studied indicating that this oxidase was crucial for protection from H2O2 in E. coli. Cell killing of all oxidase mutants by H2O2 was by an uncharacterized mechanism (mode 2 killing) with cell growth rate affected. The expression of phi(katG-lacZ), an indicator of intracellular H2O2, was 2-fold higher in a cydAB::kan mutant compared to the wild-type strain at low H2O2 concentrations (< 100 microM) suggesting that cytochrome bd mutants were experiencing higher intracellular levels of H2O2. Protein fusions to the three oxidase genes demonstrated that expression of genes encoding cytochrome bd, but not cytochrome bo' or cytochrome bd-II was increased in the presence of external H2O2. This increase in expression of 4P(cydA-lacZ) by H2O2 was further enhanced in a cyo::kan mutant. The level of cytochrome bd determined spectrally and phi(cydA-lacZ) expression was 5-fold and 2-fold higher respectively in an rpoS mutant compared to isogenic wild-type cells suggesting that RpoS was a negative regulator of cytochrome bd. Whether the effect of RpoS is direct or indirect remains to be determined.

Bacterial Proteins↗