| 1. |
- Bixo, Marie, 1957-
(författare)
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Ovarian steroids in rat and human brain : effects of different endocrine states
- 1987
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ovarian steroid hormones are known to produce several different effects in the brain. In addition to their role in gonadotropin release, ovulation and sexual behaviour they also seem to affect mood and emotions, as shown in women with the premenstrual tension syndrome. Some steroids have the ability to affect brain excitability. Estradiol decreases the electroshock threshold while progesterone acts as an anti-convulsant and anaesthetic in both animals and humans. Several earlier studies have shown a specific uptake of several steroids in the animal brain but only a few recent studies have established the presence of steroids in the human brain.In the present studies, the dissections of rat and human brains were carried out macroscopically and areas that are considered to be related to steroid effects were chosen. Steroid concentrations were measured by radioimmunoassay after extraction and separation with celite chromatography. The accuracy and specificity of these methods were estimated.In the animal studies, immature female rats were treated with Pregnant Mare's Serum Gonadotropin (PMSG) to induce simultaneous ovulations. Concentrations of estradiol and progesterone were measured in seven brain areas pre- and postovulatory. The highest concentration of estradiol, pre- and postovulatory, was found in the hypothalamus and differences between the two cycle phases were detected in most brain areas. The preovulatory concentrations of progesterone were low and the highest postovulatory concentration was found in the cerebral cortex.In one study, the rats were injected with pharmacological doses of progesterone to induce "anaesthesia". High uptake of progesterone was found and a regional variation in the formation of 5<*-pregnane-3,20-dione in the brain with the highest ratio in the medulla oblongata.Concentrations of progesterone, 5a-pregnane-3*20-dione, estradiol and testosterone were determined in 17 brain areas of fertile compared to postmenopausal women. All steroids displayed regional differences in brain concentrations. Higher concentrations of estradiol and progesterone were found in the fertile compared to the postmenopausal women.In summary, these studies show that the concentrations of ovarian steroids in the brain are different at different endocrine states in both rats and humans and that there are regional differences in brain steroid distribution.
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| 2. |
- Hellström, Anna-Lena, 1946, et al.
(författare)
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Terodiline in the treatment of children with unstable bladders.
- 1989
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Ingår i: British journal of urology. - 0007-1331. ; 63:4, s. 358-62
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Tidskriftsartikel (refereegranskat)abstract
- A double-blind study of terodiline compared with placebo was performed in 58 children aged 6 to 14 years with urgency or urge incontinence. All had an unstable bladder at cystometry. A bladder regimen was emphasised during the study. Continence was improved according to micturition charting and a pad test in both groups. Terodiline at 25 mg/day, however, gave significantly better results than placebo. In patients with a subnormal bladder capacity (less than or equal to 150 ml), a significant increase in capacity was recorded on cystometry during medication with terodiline but not with placebo. The improved continence seen in the placebo group was probably due to the non-specific bladder training achieved by the child's increased awareness and adult involvement during treatment. The even better results attained in the terodiline group shows this drug to be a valuable adjunct to a bladder regimen in children with urge incontinence, particularly since no important adverse effects were noted during an 8-week period.
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| 3. |
- Lundquist, Ingmar, et al.
(författare)
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Monoamines in pancreatic islets of guinea pig, hamster, rat, and mouse determined by high performance liquid chromatography
- 1989
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Ingår i: Pancreas. - 0885-3177. ; 4:6, s. 662-667
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies on the occurrence of catecholamines and serotonin in pancreatic islets using various histochemical and chemical methods have given widely different results. We therefore performed a comparative analysis of these amines in whole pancreas and islet tissue from hamster, guinea pig, rat, and mouse by the use of high performance liquid chromatography. Whole pancreas of guinea pig, hamster, and rat had a norepinephrine concentration of approximately 1.1 [mu]mol/kg of pancreatic wet weight. The mouse pancreas had less than one-half of that concentration. Epinephrine and dopamine concentrations were on the order of 0.02 [mu]mol/kg of pancreatic wet weight in all four species. The serotonin concentration was 2.1 [mu]mol/kg of pancreatic wet weight in the guinea pig pancreas and approximately 0.2 [mu]mol/kg in the other three species studied. The catecholamine concentrations were much higher in the pancreatic islets than in the exocrine pancreas. Thus, the norepinephrine concentration was approximately 35 [mu]mol/kg of islet wet weight in hamster islets and 5-10 [mu]mol/kg in rat, guinea pig, and mouse islets. The epinephrine concentration in islet tissue ranged between 1 and 7 [mu]mol/kg of islet wet weight and the dopamine concentration between 0.5 and 4 [mu]mol/kg except for guinea pig islets (12 [mu]mol/kg). The islet tissue in the mouse, rat, and guinea pig contained disproportionately more epinephrine and dopamine relative to norepinephrine than did the exocrine pancreas. Chemical sympathectomy (6- hydroxydopamine treatment) in the mouse reduced the norepinephrine and epinephrine concentrations in islet tissue to nondetectable levels, whereas the dopamine concentration was essentially unchanged, thus suggesting an extraneuronal source of this amine in addition to its occurrence in adrenergic nerves. The islets of hamster, rat, and mouse contained no serotonin, whereas guinea pig islets contained approximately 275 [mu]mol/kg of islet wet weight. We conclude that, although species differences exist, the pancreatic islets have markedly higher levels of catecholamines than the exocrine pancreas, and that serotonin occurs in the exocrine pancreas of all four species studied but in the endocrine pancreas only in the guinea pig.
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| 4. |
- Hellström, Anna-Lena, 1946, et al.
(författare)
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Pad tests in children with incontinence.
- 1986
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Ingår i: Scandinavian journal of urology and nephrology. - 0036-5599. ; 20:1, s. 47-50
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Tidskriftsartikel (refereegranskat)abstract
- Different pad tests were compared in 50 incontinent children. In a 2-hour ward test with standardized activities and fluid provocation 70% were positive. In a simple 12-hour home test with 30 children 68% were positive; when a fluid provocation period was included in the home test with 20 children the frequency increased to 80%. Pad tests are easy to perform with children in the home and are valuable as screening instruments. Further, the simultaneous registration of events gives a more complete picture of the incontinence pattern.
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| 5. |
- Wanders, A., et al.
(författare)
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Abolition of the effect of cyclosporine on rat cardiac allograft rejection by the new immunomodulator LS-2616 (Linomide)
- 1989
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 47:2, s. 216-7
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Tidskriftsartikel (refereegranskat)abstract
- The effect of the quinoline-3-carboxamide LS-2616 (Linomide), given alone or together with cyclosporine, was studied in the first set cardiac allograft transplantation model in the rat. PVG rat hearts were transplanted heterotopically to Wistar/Kyoto rat recipients on day 0. The recipients were given LS-2616 orally on day -1 to rejection and/or CsA orally on days 0-9. In untreated animals rejection occurred on days 8-9, as judged by the absence of palpable pulsations. Treatment with CsA (5 or 10 mg/kg) resulted in prolongation of graft survival to days 17-21, i.e., the rejection occurred 8-10 days after cessation of treatment. LS-2616 in a dose of 160 mg/kg did not in itself have any impact on graft survival, but when given in doses of 40 or 160 mg/kg simultaneously with CsA (10 mg/kg), the effect of CsA was totally abolished. Animals treated with LS-2616 together with CsA had slightly lower trough blood levels than those treated with CsA alone. This interaction with CsA pharmacokinetics does not explain the results, as doubling of the CsA dose to 20 mg/kg, which well compensated for the difference in blood levels, was not sufficient to reverse the effect of LS-2616. To our knowledge this is the first compound known to abolish the effect of CsA. The mechanism is unknown, but is is possible that studies on the interaction between these two drugs will shed further light on the molecular basis of their modes of action.
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| 6. |
- Wanders, A., et al.
(författare)
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The enhancing effect of cyclosporine A and sulfasalazine on the prevention of rejection in rat cardiac allografts
- 1988
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Ingår i: Transpl Int. ; 1:2, s. 113-5
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Tidskriftsartikel (refereegranskat)abstract
- Sulfasalazine (SASP) has been used for many years as a disease-modifying agent in inflammatory bowel disease and in rheumatoid arthritis. However, its mode of action is not entirely clear. Evidence has been accumulated which indicates that its efficacy is due to an immunomodulatory effect. In the present communication, we report that SASP has an immunomodulatory capacity in an experimental rat cardiac allograft model. A combination of 100 mg/kg per day of SASP given orally until rejection and 10 mg/kg per day of cyclosporine A (CyA) given orally for 10 days resulted in a significantly increased graft survival time as compared to that in animals given CyA alone.
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| 7. |
- Hansson, P, et al.
(författare)
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Experimental hyperthyroidism in man: effects on plasma lipoproteins, lipoprotein lipase and hepatic lipase
- 1983
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Ingår i: Hormone and Metabolic Research. - 1439-4286. ; 15:9, s. 449-452
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the effects of triiodothyronine administration (20-40 micrograms three times daily over one week) in six healthy young men, on the activities of lipoprotein lipase and hepatic lipase and on plasma lipoprotein concentrations. Hepatic lipase activity in post-heparin plasma rose by 46 +/- 25% (p less than 0.025), whereas the activity of lipoprotein lipase did not change significantly. Plasma cholesterol concentrations decreased by about 20% (p less than 0.025), whereas there was no change in plasma triglyceride levels. The fall in plasma cholesterol could be accounted for by a reduction of HDL cholesterol (-11%, p less than 0.025) as well as LDL cholesterol (-27%, p less than 0.025). The data emphasize the role of hepatic lipase in the lipoprotein alterations associated with thyroid dysfunction.
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| 8. |
- Valdemarsson, Stig, et al.
(författare)
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Hepatic lipase and the clearing reaction: studies in euthyroid and hypothyroid subjects
- 1987
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Ingår i: Hormone and Metabolic Research. - 1439-4286. ; 19:1, s. 28-30
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Tidskriftsartikel (refereegranskat)abstract
- Eight patients with primary hypothyroidism were compared to eleven euthyroid subjects with regard to the effects of a single i.v. dose of heparin on plasma lipoprotein concentrations (the "clearing reaction"). The hypothyroid patients were moderately hypercholesterolemic but had normal plasma triglyceride levels. Maximal activities of hepatic lipase (HL) and lipoprotein lipase (LPL) were lower in the hypothyroid than in the normal subjects. The hypothyroid patients demonstrated a significant decrease in total plasma cholesterol levels after heparin injection (from 8.36 +/- 0.70 mmol/l to 7.55 +/- 0.62 mmol/l, P less than 0.02). The maximal activity of HL after heparin was significantly correlated to the decrease in plasma cholesterol levels (P less than 0.05) and in LDL-cholesterol levels (P less than 0.01). The euthyroid subjects demonstrated a smaller decrease in total plasma cholesterol concentrations (from 5.53 +/- 0.31 to 5.08 +/- 0.28 mmol/l, P less than 0.05). In this group, the fall in cholesterol levels was not correlated to maximal HL activity. The reduction in plasma triglyceride levels after heparin was similar and significant (P less than 0.01) in both groups. These data support the view that decreased activity of HL contributes to the dyslipoproteinemia seen in hypothyroidism. They are also in accordance with the notion that HL is involved in the elimination of cholesterol from plasma.
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| 9. |
- Valdemarsson, Stig, et al.
(författare)
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Increase in hepatic lipase activity after testosterone substitution in men with hypogonadism of pituitary origin
- 1987
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Ingår i: Acta Medica Scandinavica. - 0001-6101. ; 221:4, s. 363-366
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Tidskriftsartikel (refereegranskat)abstract
- Ten men with hypogonadism of pituitary origin were studied before and during testosterone substitution therapy with regard to effects on the activities of hepatic lipase (HL) and lipoprotein lipase (LPL) in postheparin plasma, and on plasma lipoprotein concentrations. The mean (+/- SEM) testosterone level increased from 1.8 +/- 0.5 to 16.3 +/- 2.4 nmol/l. The mean activity of HL rose from 327.1 +/- 35.2 to 432.8 +/- 57.2 mU/ml (p less than 0.02), while the activity of LPL did not change significantly, 71.0 +/- 9.1 mU/ml before and 62.2 +/- 3.8 mU/ml after treatment. No significant alterations in lipoprotein concentrations were recorded. These results indicate that a normal testosterone level is of importance for maintaining the activity of HL in men, thereby contributing to the sex difference previously recorded for HL activity.
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| 10. |
- Valdemarsson, Stig, et al.
(författare)
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Relations between thyroid function, hepatic and lipoprotein lipase activities, and plasma lipoprotein concentrations
- 1983
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Ingår i: Acta Endocrinologica. - 0001-5598. ; 104:1, s. 50-56
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Tidskriftsartikel (refereegranskat)abstract
- Lipoprotein concentrations and activities of lipoprotein lipase (LPL) and hepatic lipase (HL) were measured in 70 subjects with thyroid function ranging from overt hypothyroidism over subclinical hypothyroidism and euthyroidism to hyperthyroidism. In parallel with serum T3 (S-T3) concentrations increasing from low in hypothyroidism to high in hyperthyroidism there were gradually higher HL activities over the full spectrum of thyroid function, accompanied by decreasing levels of total and low density lipoprotein (LDL) cholesterol. High density lipoprotein (HDL) cholesterol was lower (P less than 0.05) in hyperthyroidism than in euthyroidism but not significantly changed in the hypothyroid groups. HL was correlated to S-T3 (r = 0.77, P less than 0.001), LDL cholesterol to log S-T3 (r = -0.76, P less than 0.001), and LDL cholesterol to log HL (r = -0.55, P less than 0.001). The activity of LPL was decreased (P less than 0.001) in overt hypothyroidism compared to euthyroidism but, in contrast to HL, the activity of LPL was not increased in hyperthyroidism. The plasma triglyceride (P-TG) concentration was elevated (P less than 0.01) in overt hypothyroidism but not significantly changed in subclinical hypothyroidism or in hyperthyroidism. The LPL activity was correlated to log S-T3 (r = 0.45, P less than 0.001), P-TG to log S-T3 (r = -0.37, P less than 0.01) and P-TG to log LPL activity (r = -0.71, P less than 0.001). Our results demonstrate that thyroid hormones influence HL and LPL activities in different ways, suggesting different mechanisms of action. Changes in HL activity seem to be an important mechanism for the disturbance of cholesterol metabolism in thyroid dysfunction while the thyroid hormone influence on LPL seems to be of importance mainly for the disturbance in triglyceride metabolism.
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| 11. |
- Valdemarsson, Stig, et al.
(författare)
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Treatment of hyperthyroidism: effects on hepatic lipase, lipoprotein lipase, LCAT and plasma lipoproteins
- 1984
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 44:3, s. 183-189
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Tidskriftsartikel (refereegranskat)abstract
- The activities of hepatic lipase and of lipoprotein lipase, the elimination rate of exogenous triglyceride and the cholesterol esterification rate were determined and related to plasma lipoprotein concentrations in 16 patients before and after treatment for hyperthyroidism. The activity of hepatic lipase was significantly higher (65%) before than after treatment, while the activity of lipoprotein lipase and the elimination rate of exogenous triglyceride remained unchanged. The endogenous cholesterol esterifying ability decreased after treatment, whereas no change occurred in the fractional cholesterol esterification rate measured with normal plasma as substrate. The concentrations of LDL-cholesterol and HDL-cholesterol increased significantly after treatment. The decrease in hepatic lipase activities was correlated to the decrease in S-T3 concentrations (r = 0.77, P less than 0.001) and to the increase in HDL-cholesterol concentrations (r = 0.51, P less than 0.05). The activities of lipoprotein lipase were positively correlated to the concentrations of HDL-cholesterol both before (r = 0.54, P less than 0.05) and after (r = 0.59, P less than 0.05) treatment. These results support the view that hepatic lipase and lipoprotein lipase are both important determinants of plasma HDL concentrations and suggest that an increased hepatic lipase activity contributes to the lower HDL levels in hyperthyroid patients.
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| 12. |
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| 13. |
- Hanson, E, et al.
(författare)
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Non-neurogenic discoordinated voiding in children. The long-term effect of bladder retraining.
- 1987
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Ingår i: Zeitschrift für Kinderchirurgie : organ der Deutschen, der Schweizerischen und der Osterreichischen Gesellschaft für Kinderchirurgie = Surgery in infancy and childhood. - 0174-3082. ; 42:2, s. 109-11
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Tidskriftsartikel (refereegranskat)abstract
- Sixteen children with dysfunctional voiding without demonstrable neurological deviation were studied 6 months and five years after completed bladder retraining. The initial good effect on voiding symptoms and urinary tract infections/bacteriuria was confirmed. Moreover, the effect seems to last for several years. Bladder retraining can thus be considered a safe, cheap and relatively effective treatment in many children with symptoms of bladder dysfunction and/or recurrent urinary tract infections.
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| 14. |
- Aspenberg, P., et al.
(författare)
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Failure of bone induction by bone matrix in adult monkeys
- 1988
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Ingår i: Journal of Bone and Joint Surgery: British Volume. - 0301-620X. ; 70:4, s. 625-627
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Tidskriftsartikel (refereegranskat)abstract
- Extraskeletal bone formation can be induced in rodents by implantation of demineralised bone matrix and such implantation has been used to treat bone defects in man, but it is uncertain if induction or merely conduction occurs. We studied bone induction in primates by excising segments of the fibulae of adult squirrel monkeys, defatting and demineralising them before reimplanting them into the quadriceps of the same animal. As a control experiment, rat matrix was prepared in exactly the same way and implanted in rats. After six weeks the implants were harvested and either ashed and analysed for calcium content or prepared for histology. In the rats, the calcium content indicated that about 20% of the original matrix had been replaced by new bone. In the monkeys the calcium content was about the same as that in normal body fluid and no bone was seen in histological sections. This result casts doubt on the use of demineralised human bone matrix as a bone inductor, although it may function by other mechanisms.
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| 15. |
- Aspenberg, Per, et al.
(författare)
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Fibroblast growth factor stimulates bone formation bone induction studied in rats
- 1989
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 0001-6470. ; 60:4, s. 473-476
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Tidskriftsartikel (refereegranskat)abstract
- Implantation of demineralized bone matrix in rodents elicits a series of cellular events leading to the formation of new bone inside and adjacent to the implant. This process is believed to be initiated by an inductive protein present in bone matrix. It has been suggested that local growth factors may further regulate the process once it has been initiated. This investigation was designed to study the effect of adding a growth factor to the inductive implant. Pairs of demineralized rat femoral diaphyses were implanted intramuscularly in rats. the marrow canal of one implant in each pair was filled with a carboxymethyl cellulose gel containing 75 ng of recombinant human basic fibroblast growth factor (FGF). the other implant in each pair served as a control. It was either filled with the gel without FGF or left untreated. Bone formation was induced by all the implants after 3 weeks. the amount of mineralized tissue in the FGF-treated implants was 25 percent greater than in untreated controls. the carboxymethyl cellulose gel alone did not affect the bone yield.
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| 16. |
- Sennerby, Lars, 1960, et al.
(författare)
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Soft-tissue response to clinically retrieved titanium cover screws reimplanted in the rat abdominal wall.
- 1989
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Ingår i: The International journal of oral & maxillofacial implants. - 0882-2786. ; 4:3, s. 233-9
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Tidskriftsartikel (refereegranskat)abstract
- Clinically retrieved titanium implant cover screws (Brånemark implant system), rinsed in saline or subjected to ultrasonic cleaning and sterilization, as well as unused sterile screws were studied by scanning electron microscopy and implanted in the rat abdominal wall for 6 weeks. Irrespective of cleaning procedure, the heads of the clinically retrieved screws were covered by numerous contaminants not present on the unused screws. The reimplanted screws elicited a different tissue response than the unused screws. The tissue response to the contaminated screws was characterized by a significantly thicker fibrous capsule and by a significantly larger number of macrophages located close to the implant. Moreover, judging from their ultrastructure, studied with transmission electron microscopy, the macrophages appeared to be in a more active state when compared to those located adjacent to unused screws.
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| 17. |
- Chen, Q, et al.
(författare)
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Hydrolysis of triacylglycerol arachidonic and linoleic acid ester bonds by human pancreatic lipase and carboxyl ester lipase
- 1989
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002. ; 1004:3, s. 85-372
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Tidskriftsartikel (refereegranskat)abstract
- The hydrolysis of polyenoic fatty acid ester bonds with pure human colipase-dependent lipase, with carboxyl ester lipase (CEL) and with these enzymes in combination was studied, using [3H]arachidonic- and [14C]linoleic acid-labelled rat chylomicrons as a model substrate. During the hydrolysis with colipase-dependent lipase, the amount of 3H appearing in 1,2-X-diacylglycerol (DG) markedly exceeded that of 14C. When CEL was added in addition this [3H]DG was efficiently hydrolyzed. CEL alone hydrolyzed the triacylglycerol (TG) at a low rate. The hydrolysis pattern with human duodenal content was similar to that seen with colipase-dependent lipase and CEL in combination. Increasing the concentration of taurodeoxycholate (TDC) and taurocholate (TC) or of TDC alone stimulated the hydrolysis of [3H]- and [14C]TG, but increased the accumulation of labelled DG that could act as substrate for CEL. It is suggested that very-long-chain polyenoic fatty acids of DG formed during the action of the colipase-dependent lipase on TG containing these fatty acids may be a physiological substrate for CEL.
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| 18. |
- Barrett, Alan, et al.
(författare)
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The place of human gamma-trace (cystatin C) amongst the cysteine proteinase inhibitors
- 1984
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Ingår i: Biochemical and Biophysical Research Communications. - 1090-2104. ; 120, s. 631-636
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Tidskriftsartikel (refereegranskat)abstract
- Native γ-trace, a small basic protein present in high concentration in cerebrospinal fluid, semen and neuroendocrine cells, but of unknown biological function, is shown to be a potent inhibitor of the cysteine proteinases papain, ficin, and human cathepsins B, H and L. It proves to be the tightest-binding protein inhibitor of cathepsin B so far discovered. The name cystatin C is proposed for γ-trace to reflect the many similarities in activity and structure to chicken egg-white cystatin and mammalian cystatins A and B. The inhibition constants of cystatin C, taken together with its widespread distribution in human tissues and extracellular fluids, suggest that a physiological function could well be the regulation of cysteine proteinase activity.
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| 19. |
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| 20. |
- Belew, M, et al.
(författare)
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Structure-activity studies on synthetic analogs to vasoactive peptides derived from human fibrinogen.
- 1980
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Ingår i: Biochimica et Biophysica Acta. - 0006-3002 .- 1878-2434. ; 632:1, s. 87-94
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Tidskriftsartikel (refereegranskat)abstract
- Counterparts to two vasoactive peptides previously isolated from fibrin(ogen) degraded by plasmin (EC 3.4.21.7) were synthesized by the solid phase procedure. The synthetic undecapeptide (Ser-Gln-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys) was isolated in a homogeneous state by chromatography on Sephadex G-25 and DEAE-Sepharose CL-6B and the pentapeptide (Ala-Arg-Pro-Ala-Lys) by chromatography on BioGel P-6 and column zone electrophoresis. The effect of these two peptides and of fifteen analogs to the pentapeptide on microvascular permeability in rat skin was investigated. The two synthetic counterparts were as potent as the natural peptides. With respect to the analogs, the influence of different functional groups was first studied. This was followed by attempts to minimize the active structure, induce or relieve rigidity of the peptide back-bone or otherwise accomplish modifications by a change in chirality at critical positions. Our results show that the tetrapeptide Arg-Pro-Ala-Lys has the same effect on microvascular permeability as the pentapeptide in the assay system used. Basic amino acids at both ends, as well as a proline residue adjacent to the N-terminal amino acid appear important for full or essentially full activity. On the other hand, substitution of the Ala at position 4 with several other amino acids did not result in a significant loss in biological potency.
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| 21. |
- Borg, T, et al.
(författare)
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Prophylactic and delayed treatment with high-dose methylprednisolone in a porcine model of early ARDS induced by endotoxaemia.
- 1985
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172 .- 1399-6576. ; 29:8, s. 831-45
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Tidskriftsartikel (refereegranskat)abstract
- The effects of prophylactic and delayed treatment with high-dose methylprednisolone were evaluated in a porcine model of early adult respiratory distress syndrome induced by endotoxaemia. Spontaneously breathing pigs under ketamine anaesthesia were infused i.v. with E. coli endotoxin (10 micrograms . h-1 . kg-1) over 6h. Twenty animals received endotoxin without treatment. Eight animals were pretreated with methylprednisolone i.v., 60 mg . kg-1, followed by an i.v. infusion at a rate of 10 mg . h-1 . kg-1. Ten animals received the same dosage of methylprednisolone beginning 2 h after the start of endotoxin infusion. Pretreatment with methylprednisolone prevented the endotoxin-induced impairment in pulmonary gas exchange and the development of pulmonary oedema. The pulmonary hypertension was counteracted. Cardiac output (Qt) and O2 delivery were improved. Mean arterial blood pressure (MAP) increased and was higher than in the untreated endotoxin group. The profound fall in PMN count was inhibited, while the accumulation of these cells in the lung was still substantial. Survival was improved. Delayed methylprednisolone treatment prevented further deterioration in pulmonary gas exchange and tended to restore it towards baseline. The pulmonary oedema and pulmonary hypertension were reduced. Qt and O2 delivery did not improve. MAP was higher than in the untreated endotoxin group towards the end of the observation period. The decline in PMN count and the pulmonary accumulation of these cells were not significantly influenced. Survival was improved. These results indicate that high-dose methylprednisolone, when given early in the course of sepsis, might be of clinical value in prevention of the devastating pulmonary and circulatory complications of this disease.
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| 22. |
- Borg, T, et al.
(författare)
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The role of polymorphonuclear leucocytes in the pulmonary dysfunction induced by complement activation.
- 1985
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172 .- 1399-6576. ; 29:2, s. 231-40
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Tidskriftsartikel (refereegranskat)abstract
- To determine the role of polymorphonuclear leucocytes (PMNs) in the pulmonary reaction induced by complement activation, pigs were infused with complement-activated plasma (CAP), cell-free supernatant from PMNs activated in vitro, or washed PMN aggregates produced in vitro. Infusion of CAP resulted in transient peripheral leucopenia, a reversible rise in pulmonary vascular resistance (PVR) and decreased arterial oxygen tension (PaO2). Indomethacin did not influence the CAP-induced drop in PMN count or the accumulation of PMNs in the lung, but significantly counteracted the rise in PVR and fall in PaO2. Antihistamines did not prevent the cellular or pulmonary reactions to CAP infusion. Methylprednisolone did not inhibit the decrease in PMN count, but modified the pulmonary reaction to CAP, although it did not prevent the rise in PVR to the same extent as indomethacin; it counteracted the fall in PaO2. Infusion of supernatant from activated PMNs did not influence the PMN count, but caused a reversible increase in PVR and a drop in PaO2. Indomethacin counteracted the pulmonary reaction to this infusion. Infusion of washed PMN aggregates did not result in any cellular or physiological changes. These findings suggest that the pulmonary reaction induced by complement activation is mediated by humoral components generated and/or released during activation of PMNs. Arachidonic acid metabolites play an important role and it is likely that substance(s) released from activated PMNs trigger prostanoid synthesis in other cells. It is conceivable, however, that PMNs exposed to activated complement factors also directly synthesize and release arachidonic acid metabolites.
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| 23. |
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| 24. |
- Dahlin, Christer, 1959, et al.
(författare)
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Generation of new bone around titanium implants using a membrane technique: an experimental study in rabbits.
- 1989
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Ingår i: The International journal of oral & maxillofacial implants. - 0882-2786. ; 4:1, s. 19-25
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Tidskriftsartikel (refereegranskat)abstract
- Insufficient bone volume may be a significant problem in connection with dental implants. In this study, a technique based on the principle of guided tissue regeneration was tested for its ability to generate bone tissue around titanium implants. Implants were inserted in tibiae of rabbits. To create a secluded space for osteogenesis and to prevent soft-tissue ingrowth, a porous Teflon membrane was placed around exposed parts of the implant. Where a membrane had been used, the threads of the implant were completely covered with significant amounts of new bone. This study indicates that the membrane technique is a reconstructive surgical method that may be applicable to create new bone around exposed parts of titanium implants in a clinical setting.
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| 25. |
- Eriksson, M, et al.
(författare)
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Enhancement of the permeability-increasing effect of bradykinin and substance P by a peptide derived from fibrinogen.
- 1983
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Ingår i: International journal of microcirculation, clinical and experimental. - 0167-6865. ; 2:1, s. 53-9
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Tidskriftsartikel (refereegranskat)abstract
- Two low molecular weight fibrin(ogen) degradation products, 6A (Ala-Arg-Pro-Ala-Lys) and 6D (Ser-Gln-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys) that are known to increase vascular permeability were injected together with bradykinin, substance P, neurotensin, histamine or tuftsin into the dorsal skin of rats. Effects on microvascular permeability were evaluated as leakage of intravenously injected 125I-labelled human serum albumin to tissues. It was found that peptide 6A potentiated the leakage caused by bradykinin and also, to a minor extent, that caused by substance P over a 30 min period, but not of any other substance. Peptide 6D increased bradykinin-induced leakage to a lower degree than did peptide 6A. Thus, it is shown that products resulting from fibrinolysis exert a selective effect upon the action of bradykinin and of substance P.
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| 26. |
- Gerdin, Bengt, 1947-, et al.
(författare)
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Effect of alpha-receptor blockade on the rate of fibrin elimination from the rat lung.
- 1980
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Ingår i: Circulatory shock. - 0092-6213. ; 7:1, s. 93-101
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Tidskriftsartikel (refereegranskat)abstract
- In rats with pharmacologically blocked alpha-receptor sites intravascular coagulation was induced by an intravenous injection of thrombin. The fibrin elimination from the lungs was greatly delayed in rats treated with the alpha-receptor blocking agent phenoxybenzamine one hour before the thrombin injection; whereas, in rats given the same substance 48 hours before this injection, no influence on fibrin elimination was seen. Infusion of albumin counteracted the effect on fibrin elimination in the former rats. A synergistic effect of phenoxybenzamine and the fibrinolysis inhibitor AMCA on the elimination of fibrin from the lungs was found. Circulatory mechanisms seem most reasonably to underlie the effect of phenoxybenzamine on fibrin elimination. No changes in fibrinolysis parameters were observed.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Gerdin, Bengt, 1947-, et al.
(författare)
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Structural requirements for microvascular permeability-increasing ability of peptides. Studies on analogues of a fibrinogen pentapeptide fragment.
- 1983
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Ingår i: Biochimica et Biophysica Acta. - 0006-3002 .- 1878-2434. ; 757:3, s. 366-70
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Tidskriftsartikel (refereegranskat)abstract
- A pentapeptide, Ala-Arg-Pro-Ala-Lys, liberated from fibrinogen during plasmin-mediated fibrinolysis, was shown earlier to increase microvascular permeability in rat and human skin. Eighteen new analogues have now been synthesized in addition to the 15 previously prepared and examined for their effect on permeability. The old concept that a tetrapeptide with basic amino acids at both ends and a proline residue adjacent to the N-terminal amino acid is essential for high activity on permeability, has now been challenged. The results obtained with several of the new analogues strengthen this concept. More interestingly, however, the third amino acid, which was found in earlier studies to be less sensitive to exchange, has now been deleted as well as duplicated with only a modest loss of activity of the peptide. The chirality of the C-terminal amino acid, most surprisingly, does not seem to be crucial for peptide activity. Slightly superpotent analogues were obtained on amidation of the C-terminus. In addition, a few naturally occurring peptides, namely tuftsin, substance P, neurotensin and bradykinin, the amino acid sequences of which all exhibit characteristic features of some of our active peptide analogues were investigated in the same test system. Tuftsin displayed a potency equal to that of the pentapeptide. The other three peptides were all highly superpotent in this assay system.
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| 31. |
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| 32. |
- Heinegård, Dick, et al.
(författare)
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Cartilage proteoglycans in degenerative joint disease.
- 1987
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 14 (suppl 14):SPEC.NO., s. 110-112
-
Tidskriftsartikel (refereegranskat)abstract
- Cartilage content of proteoglycans decreases early in induced degenerative hip joint disease. Remaining molecules show structural changes indicating fragmentation. Fragments lost from the articular cartilage are released to the synovial fluid, where they can be quantified by enzyme linked immunosorbent assay. Their amounts are related to the activity of the disease process.
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| 33. |
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| 34. |
- Holtz, A, et al.
(författare)
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Spinal cord injury in rats : inability of nimodipine or anti-neutrophil serum to improve spinal cord blood flow or neurologic status.
- 1989
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Ingår i: Acta Neurologica Scandinavica. - 0001-6314 .- 1600-0404. ; 79:6, s. 460-7
-
Tidskriftsartikel (refereegranskat)abstract
- The role of a calcium-mediated increase in vascular resistance and of vascular damage caused by polymorphonuclear leukocytes (PMNLs) in the development of neurologic deficit and disturbance of spinal cord circulation following spinal cord compression was studied in the rat. Spinal cord injury was induced by 5 min of compression with a load of 35 g on a 2.2 X 5.0 mm compression plate. This caused transient paraparesis. The rats received either the calcium receptor antagonist nimodipine or an anti-rat neutrophil serum (ANS). Nimodipine was infused i.v. for 4 h in an amount of 1.5 micrograms/kg/min starting 60 min after trauma. The number of circulating PMNLs was depleted by intraperitoneal injection of an ANS raised in sheep given 12 h before trauma. This caused a reduction to about 2% of the pre-ANS value. Controls received saline or normal sheep serum. The motor performance was assessed daily on the inclined plane. On day one, the day after injury, the capacity angle had decreased from about 63 degrees preoperatively to close to 32 degrees in the experimental groups. There was then a slow improvement in both the control and experimental groups and on day 4 the capacity angle was close to 43 degrees in all 3 groups. Spinal cord blood flow, as measured with the 14C-iodoantipyrine autoradiography method, was similar in all groups on day 4. As neither the neurologic dysfunction nor the spinal cord blood flow was affected by post-trauma treatment with nimodipine or pretreatment with ANS, the possibility that calcium-mediated vasoconstriction or PMNLs play a role in the development of posttraumatic neurologic disability was not supported by this study.
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| 35. |
- Laato, M, et al.
(författare)
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Stimulation of wound healing by epidermal growth factor. A dose-dependent effect.
- 1986
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Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 203:4, s. 379-81
-
Tidskriftsartikel (refereegranskat)abstract
- This work was undertaken to study the effects of various doses of locally applied epidermal growth factor (EGF) on developing granulation tissue in rats. Cylindrical hollow sponge implants were used as an inductive matrix for the growth of granulation tissue. In the test groups, the implants were injected daily with a solution containing 0.2, 1, or 5 micrograms of EGF in 0.1% albumin while the implants of the control group were treated correspondingly with the carrier solution only. Analyses of granulation tissue in the sponge cylinders were carried out 7 days after implantation. A stimulatory, dose-dependent effect of EGF on granulation tissue formation was observed: cellularity increased, as evidenced by the elevated amounts of nucleic acids, and accumulation of collagen and glycosaminoglycans was enhanced.
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Roszkowski, W, et al.
(författare)
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Suppression of cell-mediated immune reactivity by peptides cleaved from human fibrinogen.
- 1985
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Ingår i: Upsala Journal of Medical Sciences. - 0300-9734 .- 2000-1967. ; 90:3, s. 279-91
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Tidskriftsartikel (refereegranskat)abstract
- Peptides derived from fibrinogen, known from earlier studies to inhibit the stimulation of lymphocytes in vitro and to suppress the humoral immune response in vivo, were investigated for their effect on cell-mediated immune reactivity in mice. An unfractioned mixture of peptides with molecular weights under 3,500 injected intraperitoneally at repeated intervals suppressed the contact hypersensitivity to oxazolone but did not influence the skin inflammatory reaction to croton oil. Local injections of peptides had a stronger effect on contact hypersensitivity. Four 200 micrograms local injections of peptides prior to sensitization abolished the increase in lymph node weight and the uptake of 125I-iododeoxyuridine in the draining lymph node after sensitization. Three previously isolated peptides with vasoactive effects inhibited Con A-stimulated incorporation of 3H-thymidine into spleen cells. The first, a pentapeptide (Ala-Arg-Pro-Ala-Lys), and the second, an undecapeptide (Ser-Glu-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys) both with an enhancing effect on microvascular permeability, were more potent than the third, a pentapeptide with slight vasoconstrictive properties (Thr-Ser-Glu-Val-Lys). Cell viability was not altered, as measured by trypan blue exclusion and the release of 86Rb. Accumulating evidence indicates that peptides derived from fibrin may be of importance as modulators of cellular immunoreactivity in a number of clinical conditions.
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| 40. |
- Sandler, H, et al.
(författare)
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Studies on the role of thromboxane in thrombin-induced pulmonary insufficiency in the rat.
- 1986
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Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 42:2, s. 165-75
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Tidskriftsartikel (refereegranskat)abstract
- During infusion of thrombin in rats pulmonary arterial pressure rose from 15 +/- 2 to 35 +/- 3 mmHg and mean arterial pressure fell from 120 +/- 6 to 49 +/- 27 mmHg. Plasma thromboxane B2 (TxB2) increased from 0.3 +/- 0.04 to 3.6 +/- 0.5 ng/ml. Ninety minutes later the lung weight and albumin concentration in the lung were increased (2.21 +/- 0.13 g and 22.7 +/- 4.7 mg/g) compared with controls (1.12 +/- 0.14 g and 8.5 +/- 0.9 mg/g). An inhibitor of thromboxane synthetase, Dazoxiben R, reduced the elevated pulmonary arterial pressure and the elevated plasma TxB2 concentration following infusion of thrombin. Ninety minutes after infusion of thrombin, the in vitro synthesis of TxB2 in lung tissue was increased. Dazoxiben and antineutrophil serum reduced this synthesis of TxB2 in vitro. The lung weight (2.18 +/- 0.20 g) and lung albumin concentration (21.4 +/- 3.4 mg/g) was not affected by Dazoxiben. The results indicate that TxA2 is an important mediator of the pressure changes in the early phase after infusion of thrombin and that neutrophils are associated with thromboxane formation in the lung tissue.
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| 41. |
- Stachurska, J, et al.
(författare)
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Effects of peptides cleaved from human fibrinogen by plasmin on rabbit kidney cells in culture.
- 1983
-
Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 29:4, s. 419-24
-
Tidskriftsartikel (refereegranskat)abstract
- Low molecular weight fibrinogen degradation products (LMW-FDP) containing a mixture of dialysable peptides cleaved from human fibrinogen by plasmin are cytotoxic to an established line of rabbit kidney cells and to primary cultures of rabbit kidney cells. The presence of LMW-FDP in a concentration of 50 micrograms/ml during the cell cultivation caused a considerable release of 51Cr from prelabelled cells and inhibited 3H-thymidine and 86Rb uptake. Among three isolated peptides of established primary structure only one, 6D: Ser-Gln-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys, induced a significant effect, i.e. it enhanced 3H-thymidine incorporation. Two others, 6A: Ala-Arg-Pro-Ala-Lys and 6E: Thr-Ser-Glu-Val-Lys, did not influence the examined parameters. Hence other components of LMW-FDP must be assumed to be responsible for the cytotoxic effect on kidney cell cultures.
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| 42. |
- Wallander, J, et al.
(författare)
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Small-bowel transplantation in the rat with a nonsuture cuff technique. Technical and immunological considerations.
- 1988
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Ingår i: Transplant International. - 0934-0874 .- 1432-2277. ; 1:3, s. 135-9
-
Tidskriftsartikel (refereegranskat)abstract
- Small-bowel transplantation (SBT) using an nonsuture cuff technique was carried out on 137 rats. Preparation of the donor graft was carried out according to conventional procedures. Graft perfusion was done at a fixed pressure of 35 cm water. The left renal vessels of the recipient were dissected, the native kidney removed, and the graft was connected to the vessels by a nonsuture cuff technique. Of the animals, 92% survived for at least 5 days posttransplant. Three different combinations were investigated: (1) isografts; (2) semisyngeneic grafts from nontreated Lewis----(Lewis x DA) F1 hybrids; and (3) semisyngeneic grafts from rabbit antilymphocyte globulin (ALG)-pretreated Lewis----(Lewis x DA) F1. In group 1, 80% of the grafts were unaffected after 1 month; flow studies showed slight or no impairment of circulation in the graft. In group 2, the recipients developed clinical signs of graft-versus-host disease (GVHD) after 1 week, and at the end of the 2nd week the animals showed signs of severe illness, leading to death due to GVHD. There was also a higher percentage of complications in this group. In group 3, 65% of the animals died. However, 27% showed intact grafts and no signs of GVDH after 1 month, indicating that antibody pretreatment of the donor may successfully prevent GVHD SBT.
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| 43. |
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| 44. |
- Wieloch, T., et al.
(författare)
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Product activation of pancreatic lipase. Lipolytic enzymes as probes for lipid/water interfaces
- 1982
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Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 257:19, s. 11523-11528
-
Tidskriftsartikel (refereegranskat)abstract
- During the action of pancreatic lipase and colipase on racemic 1,2-didodecanoylglycerol monolayers in the absence of bile salts, biphasic kinetics was observed under conditions of high lipid packing. Similar kinetics has earlier been reported using phospholipid-emulsified triolein droplets. These kinetics are characterized by a lag time τ(d), dependent on products accumulation at the substrate/water interface. This lag time is differentiated from the previously described enzyme concentration independent lag time τ(i) in systems of low lipid packing. Both τ(i) and τ(d) reflect a rate-limiting step due to the slow enzyme penetration into the substrate interface. The variation of τ(d) under different conditions (change in pH and concentration of Ca2+, enzyme, bovine serum albumin, and lipolytic products) lead us to propose a model for the product activation during lipolysis. We will discuss the use of the pancreatic lipase-colipase system to probe the lipid packing of emulsified triglyceride particles and lipoproteins using τ(d) as a reference value.
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