| 1. |
- Greiff, Lennart, et al.
(författare)
-
Effects of topical platelet activating factor on the guinea-pig tracheobronchial mucosa in vivo
- 1997
-
Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 160:4, s. 387-391
-
Tidskriftsartikel (refereegranskat)abstract
- Platelet activating factor (PAF) has been reported to produce a variety of airway effects including epithelial damage and increased airway-lung absorption of hydrophilic tracers. The present study examines effects of PAF on the guinea-pig tracheobronchial mucosa in vivo. Vehicle with and without PAF (4.0 and 8.0 nmol) was superfused onto the tracheobronchial mucosa. The levels of 125I-albumin, previously given intravenously, were determined in tracheobronchial lavage fluids as an index of mucosal exudation of plasma. The mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc-DTPA (a low molecular weight, 492 Da, hydrophilic tracer) was superfused onto the mucosal surface through an oro-tracheal catheter, together with vehicle or PAF (8.0 nmol). A gamma camera determined the disappearance rate of 99mTc-DTPA from the airways as an index of mucosal absorption. PAF produced dose-dependent mucosal exudation of plasma up to 20-fold greater than control (P < 0.001). However, PAF did not damage the epithelium and the absorption ability of the airway mucosa was unaffected. The results, in contrast to previous reports, suggest that PAF may not readily damage the airway mucosa even at large exudative doses of the agent. The present finding support the view that the plasticity of the epithelial junctions allows the creation of valve-like paracellular pathways for unidirectional clearance of extravasated plasma into the airway lumen. We suggest that endogenous PAF may participate in first line respiratory defence reactions by causing lumenal entry of bulk plasma without harming the epithelium.
|
|
| 2. |
- Nilsson, Bengt-Olof, et al.
(författare)
-
Effects of polyamine synthesis inhibition on polyamines, growth and mechanical properties in hypertrophic rat urinary bladder
- 1998
-
Ingår i: Pharmacology and Toxicology. - 1600-0773. ; 82:6, s. 287-294
-
Tidskriftsartikel (refereegranskat)abstract
- The polyamines putrescine, spermidine and spermine, are ubiquitous intracellular metabolites associated with growth and protein synthesis. In this study effects of polyamine synthesis inhibition on bladder growth, polyamine levels and mechanical properties were investigated in rat urinary bladder subjected to partial outflow obstruction that causes bladder hypertrophy. The S-adenosyl methionine decarboxylase inhibitor CGP-48664 (5 and 20 mg kg-1) was administered alone or in combination with the ornithine decarboxylase inhibitor DFMO (500 mg kg-1), starting one day before creation of partial outflow obstruction and then daily for 7 days. The bladder muscle level of putrescine was increased 38 times and that of spermine reduced by 4 times while spermidine was unchanged after treatment with CGP-48664 (20 mg kg-1). The increase in putrescine was abolished in animals receiving CGP-48664 in combination with DFMO. Treatment with polyamine synthesis inhibitors could not prevent or reduce the hypertrophy of the bladder as judged by bladder wet weight and protein contents. The effects on polyamine quantities were not associated with changes in Ca(2+)-force relationship or in agonist and electrically stimulated force. In summary, treatment of rats with polyamine synthesis inhibitors resulted in changes in polyamine levels in the growing urinary bladder but did not affect growth or mechanical properties.
|
|
| 3. |
- Greiff, Lennart, et al.
(författare)
-
Effects of hydrogen peroxide on the guinea-pig tracheobronchial mucosa in vivo
- 1999
-
Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 165:4, s. 415-420
-
Tidskriftsartikel (refereegranskat)abstract
- Lumenal entry of plasma (mucosal exudation) is a key feature of airway inflammation. In airways challenged with histamine-type mediators and allergen the mucosal exudation response occurs without causing epithelial derangement and without increased airway absorption. In contrast, reactive oxygen metabolites may cause mucosal damage. In this study, involving guinea-pig airways, we have examined effects of H2O2 on airway exudation and absorption in vivo. Vehicle or H2O2 (0.1 and 0.5 M) was superfused onto the tracheobronchial mucosal surface through an oro-tracheal catheter. 125I-albumin, given intravenously, was determined in tracheobronchial tissue and in lavage fluids 10 min after challenge as an index of mucosal exudation of plasma. The tracheobronchial mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc-DTPA was superfused 20 min after vehicle or H2O2 (0.1 and 0.5 M) had been given. A gamma camera determined the disappearance rate of 99mTc-DTPA from the airways as an index of airway absorption. The high dose of H2O2 (0.5 M) produced epithelial damage, increased the absorption of 99mTc-DTPA (P < 0.001), and increased the exudation of plasma (P < 0.001). Notably, it appeared that all extravasated plasma had entered the airway lumen within 10 min. These data demonstrate that H2O2 differs from exudative autacoids such as histamine by causing both epithelial damage and plasma exudation responses. These data also agree with the view that the epithelial lining determines the rate of absorption and is responsible for the valve-like function that allows lumenal entry of extravasated bulk plasma without any increased inward perviousness.
|
|
| 4. |
- Korsgren, Magnus, et al.
(författare)
-
Allergic eosinophil-rich inflammation develops in lungs and airways of B cell-deficient mice
- 1997
-
Ingår i: Journal of Experimental Medicine. - 1540-9538. ; 185:5, s. 885-892
-
Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulins (Ig), particularly IgE, are believed to be crucially involved in the pathogenesis of asthma and, equally, in allergic models of the disease. To validate this paradigm we examined homozygous mutant C57BL/6 mice, which are B cell deficient, lacking all Ig. Mice were immunized intraperitoneally with 10 micrograms ovalbumin (OVA) plus alum, followed by daily (day 14-20) 30 min exposures to OVA aerosol (OVA/OVA group). Three control groups were run: OVA intraperitoneally plus saline (SAL) aerosol (OVA/SAL group); saline intraperitoneally plus saline aerosol; saline intraperitoneally plus OVA aerosol (n = 6-7). Lung and large airway tissues obtained 24 h after the last OVA or SAL exposure were examined by light microscopy and transmission electron microscopy (TEM). The Ig-deficient mice receiving OVA/ OVA treatment had swollen and discolored lungs and exhibited marked eosinophilia both in large airway subepithelial tissue (49.2 +/- 12.0 cells/mm basement membrane [BM] versus OVA/ SAL control 1.2 +/- 0.3 cells/mm BM; P < 0.001), and perivascularly and peribronchially in the lung (49.3 +/- 9.0 cells/unit area versus OVA/SAL control 2.6 +/- 0.6 cells/unit area; P < 0.001). The eosinophilia extended to the regional lymph nodes. TEM confirmed the subepithelial and perivascular localization of eosinophils. Mucus cells in large airway epithelium increased from 1.5 +/- 0.8 (OVA/SAL mice) to 39.5 +/- 5.7 cells/mm BM in OVA/OVA treated mice (P < 0.001). OVA/SAL mice never differed from the other control groups. Corresponding experiments in wild-type mice (n = 6-7 in each group) showed qualitatively similar but less pronounced eosinophil and mucus cell changes. Macrophages and CD4+ T cells increased in lungs of all OVA/OVA-treated mice. Mast cell number did not differ but degranulation was detected only in OVA/OVA-treated wild-type mice. Immunization to OVA followed by OVA challenges thus cause eosinophil-rich inflammation in airways and lungs of mice without involvement of B cells and Ig.
|
|
| 5. |
- Persson, Carl, et al.
(författare)
-
The mouse trap
- 1997
-
Ingår i: Trends in Pharmacological Sciences. - 0165-6147. ; 18:12, s. 465-467
-
Tidskriftsartikel (refereegranskat)abstract
- Mouse models of asthma are now being used extensively in drug research. However, the successful unravelling of combinatorial interplays of cells and molecules in the murine airways may not be matched by equally successful demonstrations of an asthma-like pathophysiology. Here, Carl Persson, Jonas Erjefalt, Magnus Korsgren and Frank Sundler discuss the fact that major features of asthma may still need to be demonstrated in the airways of allergic mice.
|
|
| 6. |
- Lindqvist, Anders, et al.
(författare)
-
Long-term effects of Ca(2+) on structure and contractility of vascular smooth muscle
- 1999
-
Ingår i: American Journal of Physiology: Cell Physiology. - 1522-1563. ; 277:1, s. 64-73
-
Tidskriftsartikel (refereegranskat)abstract
- Culture of dispersed smooth muscle cells is known to cause rapid modulation from the contractile to the synthetic cellular phenotype. However, organ culture of smooth muscle tissue, with maintained extracellular matrix and cell-cell contacts, may facilitate maintenance of the contractile phenotype. To test the influence of culture conditions, structural, functional, and biochemical properties of rat tail arterial rings were investigated after culture. Rings were cultured for 4 days in the absence and presence of 10% FCS and then mounted for physiological experiments. Intracellular Ca(2+) concentration ([Ca(2+)](i)) after stimulation with norepinephrine was similar in rings cultured with and without FCS, whereas force development after FCS was decreased by >50%. The difference persisted after permeabilization with beta-escin. These effects were associated with the presence of vasoconstrictors in FCS and were dissociated from its growth-stimulatory action. FCS treatment increased lactate production but did not affect ATP, ADP, or AMP contents. The contents of actin and myosin were decreased by culture but similar for all culture conditions. There was no effect of FCS on calponin contents or myosin SM1/SM2 isoform composition, nor was there any appearance of nonmuscle myosin. FCS-stimulated rings showed evidence of cell degeneration not found after culture without FCS or with FCS + verapamil (1 microM) to lower [Ca(2+)](i). The decreased force-generating ability after culture with FCS is thus associated with increased [Ca(2+)](i) during culture and not primarily caused by growth-associated modulation of cells from the contractile to the synthetic phenotype.
|
|
| 7. |
- Agardh, Carl-David, et al.
(författare)
-
Glucose levels and insulin secretion during a 75 g glucose challenge test in normal pregnancy
- 1996
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 240:5, s. 303-309
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of the study was to evaluate glucose levels and insulin secretion early in pregnancy and at a time when gestational diabetes mellitus frequently occurs in order to define reference values for glucose tolerance during pregnancy. The results were also related to maternal factors that might identify subjects at risk of developing gestational diabetes mellitus as well as foetal factors that might be a result of impaired glucose tolerance during pregnancy. DESIGN: A prospective study. SETTING: All Caucasian women attending one antenatal out-patient care unit were offered a 75 g oral glucose tolerance test at the 17th and 32nd week of gestation. SUBJECTS: A total of 586 consecutive pregnant women were included in the study. All 586 women were examined by repeated blood glucose measurements and 298 agreed to perform oral glucose tolerance tests as well. MAIN OUTCOME MEASURES: Venous whole blood glucose values were measured in the fasting state and in samples obtained 15, 30, 45, 60, 75, 90 and 120 min after oral intake of 75 g glucose. Serum insulin and C-peptide were also measured at these times. In all subjects, a random blood glucose sample was taken at the first visit, and thereafter at the 20th, 30th and 36th week of gestation. Information was also obtained from all subjects regarding body mass index, weight gain during pregnancy, smoking habits, family history of diabetes and hypertension, hypertension during pregnancy, past obstetric history, parity, and fetal outcome. RESULTS: The glucose tolerance was significantly impaired at the 32nd week of gestation compared with the 17th week of gestation. The mean +2SD 2 h glucose value during the oral glucose tolerance test at the 32nd week of gestation was 8.0 mmol L-1. Impaired glucose tolerance was characterised by increased insulin resistance, with a significant rise in serum insulin and C-peptide concentrations and in the insulin/glucose index during the oral glucose tolerance test at the 32nd week of gestation. Maternal factors associated with an impaired glucose tolerance were a family history of diabetes mellitus, smoking, a weight gain more than 18 kg during pregnancy, and glucosuria, while a family history of hypertension and hypertension present during pregnancy were not. Foetal factors that might be a result of impaired glucose tolerance during pregnancy, e.g. macrosomia and prematurity as well as complicated deliveries such as vacuum extraction/forceps or Caesarean section, all tended to be associated with higher blood glucose values. The same pattern was seen when the Apgar score was < 7. CONCLUSIONS: The results from this study show that the present cut-off values for diagnosis of gestational diabetes mellitus should be revised. Even if some maternal factors might indicate an increased risk for impaired glucose tolerance during pregnancy, they are probably not enough to detect women with gestational diabetes mellitus. Therefore, a screening programme for gestational diabetes should be considered.
|
|
| 8. |
- Newman, D J, et al.
(författare)
-
Serum cystatin C measured by automated immunoassay : a more sensitive marker of changes in GFR than serum creatinine
- 1995
-
Ingår i: Kidney International. - : Elsevier BV. - 0085-2538. ; 47, s. 312-318
-
Tidskriftsartikel (refereegranskat)abstract
- Serum cystatin C has been suggested as a new marker of GFR. For the introduction of this marker into clinical use a rapid and automated method is required. We have developed and validated an assay for serum cystatin C using latex particle-enhanced immunoturbidimetry. Intra- and inter-assay precision were < 3% and < 5% across the assay range. Analytical recovery was 93 +/- 3.8% and no lack of parallelism was demonstrated. Regression analysis of a method comparison with an enzyme-enhanced radial-immunodiffusion method, gave PETIA = 0.074 + 0.93 x SRID, r = 0.98, N = 100. Inter-assay precision profiles showed cystatin C was measured with two-fold better precision than creatinine on the same analyzer. Cystatin C measurement was neither interfered with by icterus nor by hemolysis. 1/cystatin C versus 1/creatinine concentrations gave r = 0.67, N = 469. Comparison of Cr EDTA GFR with 1/cystatin C and 1/creatinine gave r = 0.81 and 0.50, respectively, N = 206. Calculating diagnostic sensitivity for abnormal GFR showed cystatin C to be significantly (P < 0.05) more sensitive than creatinine (71.4 vs. 52.4%). Cystatin C measurement using PETIA technology can be automated on the same instruments used routinely for the measurement of creatinine and offers better analytical performance and probably improved clinical sensitivity as a screening test for early renal damage.
|
|
| 9. |
- Nilsson, T, et al.
(författare)
-
The mechanism of binding of low-molecular-weight active site inhibitors to human alpha-thrombin.
- 1998
-
Ingår i: Journal of enzyme inhibition. - 8755-5093. ; 13:1, s. 11-29
-
Tidskriftsartikel (refereegranskat)abstract
- The thrombin inhibitors argatroban, efegatran, NAPAP, CH 1091, CH 248, inogatran and melagatran have been characterised with respect to their mechanism of binding to human alpha-thrombin. Stopped-flow spectrophotometry was used to follow thrombin-catalysed hydrolysis of the chromogenic substrate S-2238 in the presence of inhibitors. The rate of onset or decay of inhibition was evaluated using progress curve analysis. It was possible to obtain apparent association and dissociation rate constants from the dependence of the rates on the inhibitor concentrations. Inhibition constants calculated from the association and dissociation rate constants were in good agreement with those calculated from steady-state rates. The binding of 6 inhibitors was also monitored directly using stopped-flow spectrofluorimetry when two kinetic components were found with all inhibitors. The faster component accounted for the largest part of the change in the intrinsic fluorescence of thrombin induced by inhibitor binding and was dependent on the inhibitor concentration. The slower component was independent of the concentration of the inhibitor. The concentration dependence of the faster component was linear with the compounds argatroban, NAPAP, CH 1091 and melagatran and hyperbolic with the compounds CH 248 and inogatran. The values of the apparent second-order rate constants at pH 7.4 and 37 degrees C range from slow to rapid binding in the interval 16-78 x 10(6) M-1 s-1, which is somewhat higher than 1-34 x 10(6)M-1 s-1 obtained from progress curve analysis of the onset of inhibition. The present results support a mechanism that includes rearrangement of a weak initial thrombin-inhibitor complex towards a tighter complex. Moreover, at least one additional step is required in the mechanism. In this model, the rate-limiting step for the binding of the inhibitor at concentrations in the nanomolar range depends on the primary interaction between the inhibitor and native thrombin.
|
|
| 10. |
- Grimvall, E, et al.
(författare)
-
Monitoring of polychlorinated biphenyls in human blood plasma: methodological developments and influence of age, lactation, and fish consumption
- 1997
-
Ingår i: Archives of Environmental Contamination and Toxicology. - : Springer Science and Business Media LLC. - 0090-4341 .- 1432-0703. ; 32:3, s. 329-336
-
Tidskriftsartikel (refereegranskat)abstract
- Human plasma samples from 50 wives of fishermen have been analyzed with respect to PCBs. The non-ortho-substituted PCB congeners CB-126 and CB-169 were determined by mass spectrometry in negative ion chemical ionization mode, which demonstrated a limit of detection of 30 fg. The recoveries of the internal standards used for determination of ortho-substituted CBs were approximately 95%. Two methods, one gravimetric and the other based on enzymatic determinations of triglycerides, cholesterol and phospholipids, were compared for the determination of total amount of lipids in the plasma samples; the correlation coefficient was 0.82 and the slope 0.98. For practical reasons, enzymatic determinations are recommended for further use. The total, lipid-adjusted concentrations of PCBs in plasma were influenced by age, total lactation time and consumption of fatty fish from the Baltic Sea.
|
|
