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Biomedical subjects

C Svensson

Publications and source records attributed to C Svensson.

At least 91 records · Page 5Linked to original sources
PubMed1997

Permeation of polysucrose 15000 across the human nasal mucosa in vivo.

Studies of the nasal permeation of small molecules (< 1000 Da) have yielded important information about the integrity of the human airway mucosa in health and disease. In this study, we used a much larger tracer molecule, polysucrose (PS) 15,000 (approx. 14,700 Da), to predict the mucosal permeation of inhalational allergens. PS 15,000 (50 mg/ml; 15 ml), with or without a detergent type of permeation enhancer (dioctyl sodium sulfosuccinate 10 mg/ml), was maintained for 15 min in one nasal cavity of 12 healthy nonatopic subjects by employment of a nasal-pool device. Permeation as determined by the 24-h urine recovery of PS (micro-ELISA analysis assay) was expressed as percentage of nasal instillate. Mean baseline permeation was 0.044% (range 0.009-0.250%). In the presence of the detergent, permeation increased to 0.600% (range 0.007-2.260%) (P < 0.01). After oral intake of 750 mg of PS 15,000 (50 micrograms/ml; 15 ml), the 24-h urinary recovery was 0.013% (range 0.004-0.023%). Our study thus demonstrates a measurable baseline permeation of PS 15,000, an elevated permeation rate in the presence of an epithelium-damaging detergent molecule, and a negligible permeation by the oral route. These properties support the utility of PS 15,000 as a nasal airway permeation tracer. Its size further suggests that its permeation may reflect mucosal perviousness to many allergens.

Adult↗
PubMed1997

The "nasal pool"-device for challenge and lavage of the nasal mucosa in children: histamine-induced plasma exudation responses.

The accessibility of the nasal airway allows important examination of the airway mucosa in health and disease. However, the current methods for nasal challenge and lavage in children suffer from several shortcomings. In the present study, we have assessed the utility of a recently developed "nasal pool"-device in 7-9 year old children, and explored the ability of the nasal mucosa of these school-children to mount a plasma exudation response (lumenal entry of bulk plasma). Isotonic saline was instilled and maintained (1 min) as a "pool" in the unilateral nasal cavity. Recovery of the "pool" (lavage fluids) was determined. Concomitant challenge and lavage was then performed by exposing the nasal mucosa to a "pool" of isotonic saline and histamine (40-400 micrograms/ml) for 2 min. "Pool" fluids were analysed for alpha 2-macroglobulin as an index of microvascular-epithelial exudation of bulk plasma. The school-children successfully managed to carry out nasal lavages as well as concomitant histamine challenges and lavages with the "nasal pool"-device. The recovery of the nasal lavage fluids was almost quantitative (> 85%) and thus well reproducible. Histamine produced significant exudation of bulk plasma (alpha 2-macroglobulin). We suggest that the "nasal pool"-device is well suited for challenge and lavage of the nasal airway mucosa in children above 6 years of age, and conclude that lumenal entry of multipotent humoural protein-systems may be an important first line respiratory defence mechanism in children.

Child↗
PubMed1997

Effects of inhaled histamine, methacholine and capsaicin on sputum levels of alpha 2-macroglobulin.

BACKGROUND: Plasma exudation-derived proteins and peptides contribute significantly to inflammation in the airway mucosa in vivo. In the guinea pig trachea both histamine and the neurogenic stimulant capsaicin produce acute mucosal tissue distribution and luminal entry of bulk plasma, whereas cholinergic agonists fail to produce this effect. Of these agents, only histamine induces mucosal exudation of plasma in human nasal airways. The exudative effect of the above agents on human bronchi remains unknown. METHODS: The bronchial exudative responses to inhalation of histamine, methacholine, and capsaicin were examined in two groups of healthy volunteers. Sputum was induced on three occasions in each study group by inhalation of hypertonic saline (4.5%) given as an aerosol for 40 minutes using an ultrasonic nebuliser. The second and third occasions were preceded by histamine and capsaicin challenges in the first study group, and by histamine and methacholine challenges in the second study group. Histamine and methacholine were given in cumulative doses (total doses 3160 micrograms, respectively) or until a 20% reduction in forced expiratory volume in one second (FEV1) was achieved. Cumulative doses of capsaicin were inhaled until coughing prevented the subjects from drawing a full breath. Sputum levels of alpha 2-macroglobulin (729 kDa) were measured as an index of mucosal exudation of bulk plasma. RESULTS: Histamine increased mean (SE) sputum levels of alpha 2-macroglobulin from 2.72 (1.01) micrograms/ml (95% confidence interval (CI) 0.49 to 4.94) to 18.38 (8.03) micrograms/ml (95% CI 0.49 to 36.27) in the first group, and from 1.66 (0.84) micrograms/ml (95% CI -0.18 to 3.49) to 9.43 (3.63) micrograms/ml (95% CI 1.59 to 17.27) in the second group. In contrast, capsaicin evoked no exudation (sputum levels of alpha 2-macroglobulin 1.21 (0.28) micrograms/ml (95% CI 0.59 to 1.83)) and methacholine produced a minor increase in sputum levels of alpha 2-macroglobulin (2.90 (0.92) micrograms/ml (95% CI 0.90 to 4.89)). CONCLUSIONS: These results indicate that histamine is a useful agent for studying bronchial exudative responsiveness in man and that exudative effects are only of marginal importance in the cough and bronchoconstriction produced by capsaicin and methacholine.

Administration, Inhalation↗
PubMed1997

Reduced airway absorption in seasonal allergic rhinitis.

The common notion that increased mucosal absorption characterizes allergic and inflamed airways is poorly supported by physiologic in vivo data. We have now examined whether the airway mucosa of patients with seasonal allergic rhinitis develop a change in absorption during their active disease period. Twelve patients with birch pollen rhinitis were examined twice, prior to and late into a Swedish birch pollen season. Ten healthy subjects were examined once. A nasal pool device was used to fill the unilateral nasal cavity with fluid containing 1-deamino-8-D-arginine vasopressin (desmopressin, 20 micrograms/ml) as absorption tracer. The peptide tracer solution was removed after 15 min, and absorption was determined by analysis of the peptide in the 24-h urine sample. Nasal absorption did not differ between healthy subjects and symptom-free patients outside the season. After 3 wk of symptom-producing seasonal allergic rhinitis, absorption of the peptide across the nasal mucosa was less (p < 0.05) than outside the season. These data indicate that hyperresponsiveness and disease progression in seasonal allergic rhinitis are not due to a compromise of the mucosal barrier that would permit increased absorption of mucosally deposited solutes. The reduced absorption may in part reflect the ability of the airway epithelium in vivo to maintain and potentially improve its barrier function by efficient epithelial restitution processes.

Absorption↗
PubMed1997

Topical azelastine has a 12-hour duration of action as assessed by histamine challenge-induced exudation of alpha 2-macroglobulin into human nasal airways.

BACKGROUND: Oral anti-histamine drugs are widely used in the treatment of seasonal allergic rhinitis. Recently, anti-histamines have become available also for topical treatment. OBJECTIVE: The present study, involving healthy subjects, examined the effect of topical azelastine on luminal entry of alpha 2-macroglobulin and symptoms evoked by repeat histamine challenges during 24 h. The effect was compared to a clinical dose of the oral anti-histamine cetirizine and to placebo treatments. METHODS: Placebo and azelastine (0.254 mg per nasal cavity) were delivered as two consecutive actuations per nasal cavity using a nasal spray device. Oral placebo and cetirizine (10 mg) were given as single doses in a placebo-controlled (double-dummy), double-blind, and cross-over design. Histamine-challenges were given 1 h before treatment, and 1, 6, 9, 12, and 24 h after each treatment. The nasal mucosal surface was lavaged after each challenge. The lavage-fluid levels of alpha 2-macroglobulin were determined to assess mucosal exudation of bulk plasma, and nasal symptoms were scored. RESULTS: Histamine (40-400 micrograms/mL) produced dose-dependent exudation and symptoms. Compared between each treatment and placebo, azelastine and cetirizine reduced the 40 and/or 400 micrograms/mL histamine-induced mucosal exudation of plasma from 1-12 h after treatment. In addition, cetirizine reduced the 40 micrograms/mL histamine-induced mucosal exudation of plasma 24 h after treatment. Differences between the two treatments were not evident regarding nasal symptoms. CONCLUSION: Histamine challenge-induced mucosal exudation of plasma appears to be a useful method for studies of the duration of action of antihistamines. We conclude that topical azelastine is suited for b.i.d. therapy and that neither the exudative process nor watery secretion may impede the efficacy or the duration of action of this nasal drug.

Administration, Intranasal↗
PubMed1997

Effects of two weeks of topical budesonide treatment on microvascular exudative responsiveness in healthy human nasal airways.

Extravasation and luminal entry of plasma (mucosal exudation) is not only a key feature of airway inflammation in rhinitis and asthma but also a major first-line respiratory defence mechanism. Topical steroids are effective antiexudative agents in disease but, so far, little is known about the direct effects of these drugs on the responsiveness of the microcirculation in human airways. In this study, the effects of prolonged budesonide treatment on histamine-induced mucosal exudation of plasma was examined in 42 healthy subjects. Placebo and budesonide (100 microg per nasal cavity b.i.d.) were given for 2 weeks in a double-blind and placebo-controlled parallel-group protocol. Using a nasal pool technique, nasal challenges with isotonic saline and histamine (40 and 400 microg x mL(-1)) were carried out before and late in the treatment periods. The lavage fluid levels of alpha2-macroglobulin were measured as an index of mucosal exudation of bulk plasma. Histamine produced concentration-dependent mucosal exudation of plasma before as well as after treatment with either placebo or budesonide. The topical steroid treatment only marginally (1.8 fold) decreased the response to the low concentration histamine (40 microg x mL(-1)) and, although it was significantly (2.8 fold) reduced, histamine 400 microg x mL(-1) still produced significant mucosal exudation of plasma in the budesonide group. If the present observations are extrapolated to inflammatory conditions, the antiexudative effects of topical steroids in rhinitis (and asthma) may reflect only a small degree of microvascular antipermeability effects. We suggest that topical steroid treatment may not impede mucosal exudation responses when called for in acute human airway defence reactions.

Administration, Intranasal↗
PubMed1996

The CtBP binding domain in the adenovirus E1A protein controls CR1-dependent transactivation.

The adenovirus E1A-243R protein has the ability to force a resting cell into uncontrolled proliferation by modulating the activity of key targets in cell cycle control. Most of these regulatory mechanisms are dependent on activities mapping to conserved region 1 (CR1) and the non-conserved N-terminal region of E1A. We have previously shown that CR1 functions as a very patent transactivator when it is tethered to a promoter through a heterologous DNA binding domain. However, artificial DNA binding was not sufficient to convert full-length E1A-243R to a transactivator. Thus, an additional function(s) of the E1A-243R protein modulates the effect of CR1 in transcription regulation. Here we demonstrate that a 44 amino acid region at the extreme C-terminus of ElA inhibited transactivation by a Gal4-CR1 fusion protein. Inhibition correlated with binding of the nuclear 48 kDa C-terminal binding protein (CtBP), which has been implicated in E1A-mediated suppression of the metastazing potential of tumour cells. This might suggest that CtBP binding can regulate E1A-mediated transformation by modulating CR1-dependent control of transcription.

Adenovirus E1A Proteins↗
PubMed1996

Background factors in patients with schizoaffective disorder as compared with patients with diabetes and healthy individuals.

Family history and psychosocial background factors were studied in married patients with a DSM-III diagnosis of schizoaffective disorder (n = 17, partners n = 16), married patients with diabetes (n = 10, partners n = 10) and married healthy individuals (n = 8, partners n = 8). The two latter groups were comparison control groups matched for gender and age to the patients with schizoaffective disorder. Affective disorder, not particularly schizoaffective disorder, was more common in first- and tended to be more common in second-degree relatives of patients with schizoaffective disorder as compared with controls. Poor parental relations, especially to the father, during the formative years were prominent in patients with schizoaffective disorder as compared with the controls. The same patients also more often than others gave a report of sexual encroachment, inside or outside the family, and corporal punishment during the growing-up years.

Adult↗
PubMed1996

Growth resistance-sized arteries in response to bladder hypertrophy in the rat: time-course, DNA-synthesis and LDH-isoform pattern.

Bladder growth was induced by partial urethral obstruction. Bladder hypertrophy was evident at 53 h after obstruction and continued over a 6 weeks period. Small bladder arteries were taken from fixed anatomical locations of the bladder circulation, mounted in a small vessel myograph and the optimal diameter for maximal isometric force development was determined (Lmax K+ = 125 mM stimulation). Bladder hypertrophy was associated with an enlarged Lmax from 53h onward (compared with sham-operated controls) and Lmax continued to increase until 10 days after urethral obstruction. Between 10 days and 6 weeks no further increase of the diameter was observed. Increased diameters in vitro were accompanied by a transiently increased [3H] Thymidine uptake in the small arteries which peaked at 53 h after obstruction but was still above background at 10 days. At this time point, small arterial growth was associated with a significant relative increase in the M isoform of LDH as determined with agarose electrophoresis on tissue homogenates. Thus organ growth induced small vessel growth in the rat is characterized by a rapid onset, increased but transient DNA-turnover and LDH-isoform changes. The latter mimic changes seen in other types of smooth muscle growth.

Animals↗
PubMed1996

Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer.

BACKGROUND: In certain patients with pancreatic and biliary cancer, chemotherapy may relieve tumour-related symptoms, improve quality of life and possibly prolong survival. The extent of these improvements is not completely known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in patients with pancreatic and biliary cancer. PATIENTS AND METHODS: Between January 1991 and February 1995, 90 eligible patients with pancreatic or biliary cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was either sequential 5-fluorouracil/leucovorin combined with etoposide (FELv) or, in elderly and poor performance patients, the same regimen without etoposide (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument. RESULTS: Mean scale scores in the QLQ-C30 improved more often/deteriorated less frequently in the chemotherapy group than in the best supportive care group. More patients in the chemotherapy group (36%, 17/49) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (10%, 4/41, P < 0.01). Overall survival was significantly longer in the chemotherapy group (median 6 vs. 2.5 months, P < 0.01). Also, the quality-adjusted survival time was longer for patients randomized to chemotherapy (median 4 vs. 1 months, P < 0.01). The effects were seen both in pancreatic and biliary cancer. CONCLUSIONS: The results show that chemotherapy can add to both quantity and quality of life in advanced pancreatic and biliary cancer. The number of patients who benefit from treatment is, however, still limited; for this reason careful selection before, and close monitoring during, treatment are necessary.

Adult↗
PubMed1996

Effects of growth hormone in vitro on the glucose metabolism of fetal rat islet beta-cells.

This study was undertaken to investigate the effects of growth hormone (GH) on the in vitro maturation of the metabolism of fetal rat islets. For this purpose fetal islets were obtained from 21-day-old fetuses by mild collagenase digestion of the pancreas and cultured in RPMI 1640 supplemented with 10% fetal calf serum. After one day the medium was changed and supplemented with 1% fetal calf serum with or without GH (1 microgram/ml, human recombinant) and the islets cultured for another two days. Islets were then studied with regard to insulin secretion, (pro)insulin and total protein biosynthesis, glucose utilization and oxidation, thymidine incorporation, insulin and DNA contents and the contents of mRNAs for either insulin, adenine nucleotide translocator or cytochrome b. In addition, the activities of glucose phosphorylating enzymes and succinate-cytochrome c reductase were measured. Islets treated with GH showed increased insulin secretion in response to glucose, increased rates of glucose oxidation and utilization, increased thymidine incorporation and increased activities of succinate cytochrome c reductase and glucose phosphorylation at high glucose concentrations. There were, however, no changes in (pro)insulin and total protein biosynthesis, contents of insulin and DNA or the contents of any of the mRNAs. These combined data show that fetal beta-cells are sensitive to growth hormone with respect to glucose metabolism, insulin release and DNA replication. The increased rates of islet glucose phosphorylation may reflect glucokinase activity and explain part of the increased insulin responsiveness to glucose of the fetal rat beta-cell. These observations suggest that GH is of physiological significance for the maturation of the fetal beta-cell.

Animals↗
PubMed1996

Day-night differences in mucosal plasma proteins in common cold.

Aggravation of symptoms in inflammatory airway diseases is common in the early morning hours, but little is known about day-night differences in the occurrence of plasma exudate on the airway surface. We have therefore examined the plasma macromolecules on the nasal mucosa at different time points. The study comprised 20 subjects who had been inoculated (day 0) with coronavirus intranasally. Ten subjects remained healthy and 10 developed common cold with significant symptoms from day 2 to day 6. Starting on day 3 at 8.00 h and repeated at 4 h intervals until 4.00 h on day 4, nasal lavages were carried out by employment of a nasal pool-device which fills the entire unilateral nasal cavity and gently but effectively irrigates its surface. Lavage fluid levels of albumin (Mw 69,000 D) and fibrinogen (Mw 340,000 D) were determined. In the healthy subjects the levels of albumin and fibrinogen remained low throughout the experiment, however, with mean peak values of the two proteins occurring at 4.00 h (p < 0.05 compared to daytime nadir at 16.00 h). In subjects with common cold both albumin (p < 0.05) and fibrinogen (p < 0.01) exhibited marked variation with individual and mean peak levels recorded at 8.00 h day 3, and 4.00 h day 4. These mean peak values were 5-20 times higher (p < 0.01 - p < 0.05) than the mean levels recorded in these subjects at the other time periods. The present data indicate a marked day-night difference in the occurrence of plasma proteins on the airway surface in common cold, whereas in health the difference is much less. We conclude that different-sized plasma proteins may accumulate on the mucosa in healthy airways during late night hours and that in common cold this nocturnal accumulation may be considerably increased.

Adult↗
PubMed1996

Eimeria alabamensis coccidiosis in grazing calves: control by a long-acting baquiloprim/sulphadimidine bolus.

The excretion of Eimeria oocysts, the faecal dry matter and the weight gain of three groups of 12 calves, were compared during their first 20 days of grazing on a pasture known to have been contaminated with oocysts of Eimeria alabamensis during the previous year. On the day of turnout (day 0) the calves in group 1 were each treated with one bolus per 200 kg bodyweight containing 1.6 g baquiloprim and 14.4 g sulphadimidine. The calves of group 2 received the same treatment on day 3, and the calves of group 3 were left untreated. Eleven of the untreated calves developed clinical coccidiosis due to E. alabamensis and excreted more than 850,000 oocysts/g of faeces 8-10 days after turnout. Seven of the calves in group 1 and five of those in group 2 developed diarrhoea, but it was milder and/or less persistent than in the untreated calves. The treated calves excreted significantly fewer oocysts and lost significantly less weight than the untreated calves. On day 21 all the calves were housed and on day 27 they were challenged with 10 million sporulated oocysts of E. alabamensis and turned out on to the same pasture. Only minor clinical signs were observed in some of the calves, indicating development of immunity in all groups. However, there was a tendency for the calves treated on day 3 to excrete more oocysts and to gain less weight than the other calves.

Animals↗
PubMed1996

Immunisation of calves against Eimeria alabamensis coccidiosis.

Twelve calves which had been immunised with a trickle dose of altogether 100,000 oocysts of Eimeria alabamensis 16 days before turnout and 12 uninoculated calves were monitored during their first 20 days of grazing on a pasture naturally contaminated with oocysts of E. alabamensis. Eleven of the uninoculated calves developed gruel-like diarrhoea 3-6 days after turnout and excreted more than 850,000 oocysts/g of faeces (OPG) a few days later. In contrast, none of the immunised calves developed clinical coccidiosis and most of them excreted only a few oocysts. They lost on average 18 kg less in bodyweight than the unimmunised control calves. On day 21 all the calves were rehoused and on day 27 they were challenged with 10 million sporulated oocysts of E. alabamensis and turned out onto the same pasture. Only insignificant clinical signs were observed in 2 of the immunised calves and in one of the control calves. It was concluded that immunisation is a promising control measure for E. alabamensis coccidiosis. However, fewer or attenuated oocysts must be used, as 9 of the 12 inoculated calves developed clinical coccidiosis before turnout as a result of the immunisation doses.

Animals↗