One-step and two-step description of deexcitation processes in weakly interacting systems.
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Biomedical subjects
Publications and source records attributed to A Nilsson.
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The metabolism in vivo in the rat of 125I-prothrombin-chylomicron complexes was compared to that of free 125I-prothrombin injected in saline or together with chyle chylomicrons. The group that obtained 125I-prothrombin-chylomicron complexes exhibited a faster initial decrease of plasma 125I-prothrombin, a higher radioactivity in the liver and more trichloroacetic acid soluble 125I in plasma than in the other groups that did not differ. In the group injected with 125I-prothrombin-chylomicron complexes, 4% was in the HDL, 0.7% LDL, and 0.8% in VLDL 2 hours after injection. The data thus indicate that although most of the 125I-prothrombin is released during the metabolism of the prothrombin-chylomicron complexes, some is rapidly degraded and some is transferred to plasma lipoproteins and remains circulating for a considerable time period. The observations demonstrate that binding to chylomicrons influences the catabolism of prothrombin in vivo. Since chylomicrons did not influence the clearance of simultaneously injected free 125I-prothrombin, the prothrombin binding to chylomicrons or chylomicron remnants in vivo may, however, be too slow to influence the prothrombin catabolism under normal conditions.
Growth hormone (GH) is known to be of a major importance for longitudinal bone growth, but its local effects on osteogenesis and, thus, regeneration of bone defects are less known. The aim of this investigation was to study whether GH, systemically or locally administered, has any stimulatory effects on local osteogenesis, utilizing standardized, membrane-covered, transosseous defects (5 mm diameter) in mandibles of adult albino rats. The study also addressed the question of whether GH might be a feasible option to further promote bone regeneration and neogenesis in conjunction with expanded polytetrafluoroethylene (e-PTFE) "osteopromotive" membranes (GORE-TEX). Human GH (hGH; 0.2, 2, 20, 200 micrograms/day), bovine GH (bGH; 200 micrograms/day), prolactin (200 micrograms/day) or saline was administered systemically by means of mini-osmotic pumps, implanted subcutaneously at the back of the animal. Healing was analyzed after 2, 3, and 4 weeks. Healing was also studied after local administration, just outside the defects, of hGH (0.2, 2, 20 micrograms/day) via catheters connected to mini-osmotic pumps during 4 weeks. Human GH and bGH stimulated local bone formation compared to saline and prolactin. Bone formation was significantly promoted by systemically administrated hGH, after 3 weeks and at 2 micrograms/day or higher concentrations. Enhanced bone formation was also found after 4 weeks in animals given 0.2, 2 and 20 micrograms/day of hGH locally, compared to local administration of saline. The results show that GH exerts a direct, nonliver mediated effect on bone tissue. Moreover, the study suggests that hGH may be used to stimulate bone healing and formation in conjunction with osteopromotive membranes.
The alkaline sphingomyelinase (SMase) was first found in rat intestinal brush border. The important roles of this enzyme in digestion of sphingomyelin and in mucosal cell proliferation have been suggested. In the present work, the distribution of the alkaline SMase in the tissues of human beings and animals have been studied. By assaying the enzyme activity in human biopsy samples, we found that the alkaline SMase activity was absent in the stomach, increased in the duodenum, present at high levels in the small intestine, and slightly declined in the colon and rectum. High activities were found similarly in the intestinal contents of the healthy adults and infants. The activities were also found in the intestinal mucosa of rats, normal and germ-free mice, and hamsters with the same distribution pattern as in humans, but not in the intestinal mucosa of guinea pigs. Apart from the intestinal tract, a SMase activity preferring alkaline pH was identified in human and guinea pig bile, but not in the bile of rat, pig, sheep, and cow. No activity was found in either pancreatic tissue or pancreatic juice in all species tested, and none was detected in human urine and milk. In conclusion, alkaline SMase exists predominantly in the digestive system with considerable tissue and species differences.
Disposition of intravenous anaesthetic eltanolone was studied when administered as a bolus injection (B) of 0.75 mg/kg and constant rate intravenous infusion at 2 mg/kg/hr (12) and 3.5 mg/ kg/hr (13.5) for 2 hr in healthy male volunteers. Venous blood samples were collected for 12 hr and 20 hr following bolus injection and intravenous infusion, respectively. Serum eltanolone concentrations were determined by a specific gas chromatographic mass spectrometric assay. Using a nonlinear regression analysis, the individual data sets were best fitted by a three-compartment mamillary model with central elimination. Derived pharmacokinetic parameters expressed as median and 95% confidence intervals indicated an initial fast distribution with a half-life of 1.80 (0.23-5.47) min (B), 1.44 (0.97-2.06) min (12) and 1.44 (0.95-2.39) min (13.5), an intermediate phase with a half-life of 35.4 (28.7-45.2) min (B), 39.6 (31.0-47.9) min (12) and 35.4 (33.3-44.9) min (13.5) and a moderately short terminal phase with a half-life of 3.8 (2.7-5.9) hr (B), 5.0 (4.2-6.1) hr (12) and 4.6.(4.0-4.8) hr (13.5). The serum clearance after bolus injection was 1.37 (1.23-1.67) L/hr/kg and after infusion was 1.36 (1.25-1.52) L/hr/kg (12) and 1.17 (1.11-1.31) L/hr/kg (13.5). The pharmacokinetics of eltanolone appear to be linear over the dosage range studied. Pharmacokinetic parameters obtained after bolus injection were very much similar to the parameters obtained after infusion with the exception of t1/2 beta which was longer after the infusion (significant) and the volume of central compartment which was lower after infusion (not significant). Context sensitive times were estimated for a 30%, 50% and 80% drop in the concentration of eltanolone after different infusion times. A 30% drop in concentration is estimated to take about 2 to 3 min. A 50% drop in concentration is estimated to take about 8 min when duration of infusion is 3 hr and reaches a value of about 10 min by a duration of infusion of 10 hr. A 80% drop in concentration is estimated to take about 55 min following an infusion of 1 hr and it reaches a value of 70-80 min following an infusion of 10 hr.
Arachidonic acid (AA) functions as a structural component, eicosanoid precursor and surface material for chylomicron production in the gastrointestinal tract. The origin of this AA is poorly characterized. [3H]AA labelled chylomicrons and [14C]AA albumin-FFA were injected intravenously into biliary diverted rats and controls. Radioactivity in tissue lipids was measured after different time intervals. Output of 3H and 14C in bile was 8% of the injected dose during 24 h. Radioactivity of the upper small intestine but not of colon and stomach increased with time. Bile drain reduced the recovered amounts of radioactivity in upper small intestine by 75% after 24 h. In stomach and colon 3H/g tissue was 16-20 fold lower than in liver after 24 h. Recovery of 3H in liver was higher than of 14C. In liver 3H/g tissue was 15-40 fold higher than in stomach and colon after 10-60 min. Equilibration between AA pools of liver and other organs was not complete after 96 h. Biliary phospholipid is an important source of AA for the small intestine.
Spontaneous and tardive dyskinesias were studied in a random population sample of 446 men, aged 59 years. Dyskinesia, defined as an AIMS score of at least 2 in any body part, was seen in 15.1% (n = 74). Dyskinetic men had a higher cigarette consumption, and they had higher frequencies of psychiatric morbidity and exposure to neuroleptics. Dyskinesia was also associated with several abnormalities in EFA concentrations in plasma, but the most consistent finding was the low arachidonic acid levels in phospholipids, triglycerides and cholesterol esters. In a logistic regression model, cigarette consumption (P < 0.02), exposure to neuroleptics (P < 0.01), and low arachidonic acid levels in the phospholipid fraction (P < 0.0001) were independently associated with dyskinesia.
OBJECTIVE: To determine whether bladder distension affects venous haemodynamics during transurethral resection of the prostate (TURP) such that irrigating fluid is more easily absorbed. PATIENTS AND METHODS: The right common femoral vein was examined using an ultrasound Doppler blood-flow scanner in 10 patients (mean age 73 years, range 63-80) undergoing TURP. Measurements of blood flow were performed before, during and after the bladder was filled with irrigating solution. Fluid absorption was measured by the ethanol method. RESULTS: Measurements before, half-way through and immediately after the resection all showed that the luminal diameter and the cross-sectional area of the femoral vein increased significantly when the bladder was filled with irrigating fluid. Furthermore, a decrease in the normal variation of blood flow with breathing often occurred when the bladder was filled, indicating that proximal venous obstruction was the cause of the increase in vessel diameter. However, there was no apparent association between these changes and the absorption of irrigating fluid. CONCLUSIONS: Filling the bladder with irrigating fluid with the patient in the lithotomy position during TURP was followed by signs of iliac venous obstruction but this did not correlate with the absorption of irrigating fluid.
OBJECTIVE: To study whether moderate amounts of irrigating fluids induce cardiac stress when infused into healthy volunteers, giving special attention to solutions containing ethanol as a tracer of absorption. SUBJECTS AND METHODS: Over a period of 20 min, 15 mL/kg of glycine (1% or 1.5%) or 3% mannitol (all containing 1% ethanol) or sorbitol 2%-mannitol 1% (with no ethanol) were infused intravenously into 10 healthy male volunteers. The central haemodynamic responses were studied using Doppler ultrasonography. RESULTS: Specific and general haemodynamic responses were observed. After infusing glycine there was a reduction of the heart rate and in cardiac output and an elevation of mean arterial pressure, indicating an increase in systemic resistance. There was no improvement when the glycine content was reduced from 1.5% to 1.0%. Furthermore, infusion of all irrigating fluids was associated with a decrease in cardiac output 30 min after the infusion. Almost identical breath-ethanol curves were obtained with the three fluids containing ethanol and all of them caused slight hypoglycaemia. There was no evidence of ethanol-induced tachycardia. CONCLUSIONS: Irrigating fluids containing glycine and ethanol have a specific haemodynamic effect not occurring with solutions containing mannitol or sorbitol.
BACKGROUND & AIMS: Systemic glucocorticosteroids (GCSs) have proven efficacy in active ulcerative colitis but cause undesired systemic side effects. Therefore, new GCSs with high topical activity and a high rate of metabolism may be of clinical value in this condition. The aim of this study was to explore the efficacy and safety of the topically acting GCS budesonide in an oral controlled-release formulation in extensive or left-sided, mild to moderately active ulcerative colitis. METHODS: A 9-week, randomized, double-blind, controlled trial was performed, and treatments with 10 mg budesonide or 40 mg prednisolone daily, both gradually tapered, were compared. Endoscopic improvement and effect on endogenous plasma cortisol were assessed. RESULTS: Thirty-four patients were administered budesonide, and 38 patients were administered prednisolone. Mean endoscopic scores improved significantly in both groups but without difference between the groups. Five patients in the budesonide group and 7 patients in the prednisolone group deteriorated and were withdrawn from the study. Morning plasma cortisol levels were suppressed in the prednisolone group (entry, 449 nmol/L; 2 weeks, 116 nmol/L; 4 weeks, 195 nmol/L) but were unchanged in the budesonide group. CONCLUSIONS: The GCS budesonide administered in an oral controlled-release formulation seems to give an overall treatment result in active ulcerative colitis approaching that of prednisolone but without suppression of plasma cortisol levels. This concept merits further evaluation.
Hyperlipidaemia frequently accompanies infectious diseases and may be due to an increase in lipoprotein production or a decrease of lipoprotein clearance. The administration of endotoxin has been used to mimic infection and previous studies have demonstrated that endotoxin induces an increase in low density lipoprotein (LDL) levels. In the present study in rats, the dose of endotoxin (055:B5, 50 micrograms 100 g body weight-1) induced hyperlipidaemia without shock and death. The clearance of 125I-LDL was measured after simultaneous injection of 100 micrograms LDL protein with endotoxin or without endotoxin (control). Endotoxin significantly inhibited the clearance of 125I-LDL from blood at all time intervals between 1 and 24 h. The total 125I and trichloroacetic acid-(TCA) precipitable 125I in the liver was higher in endotoxin-treated animals than in controls after 0.5, 4 and 24 h. An increased tissue radioactivity was also seen in several other tissues at various time intervals in the endotoxin treated group. The increase in plasma triglyceride induced by endotoxin reached a maximum after 8 h. Endotoxin thus causes a rapid inhibition of both the LDL disappearance from blood and of the LDL degradation after the uptake by the liver. This effect precedes the increase in triglyceride levels. The inhibition of the LDL catabolism may contribute to the rise in LDL levels in endotoxin induced hyperlipidaemia.
This report describes the production and characterization of transgenic mice with high expression of human cellular retinol-binding protein type I [hCRBP(I)]. In initial experiments, overexpression of hCRBP(I) was driven by the strong promoter SR(alpha), but no transgenic offspring were produced. When we used the less efficient mouse metallothionein I promoter fused to the hCRBP(I) cDNA for microinjection, we obtained 12% transgenic offspring. Two of these transgenic mice (409/1 and 401/2) expressed mRNA and immunoreactive hCRBP(I) in several organs. Both lines had relatively high contents of hCRBP(I) in intestine, testis and epididymis. On the other hand, only 401/2 transgenic mice had high contents of hCRBP(I) in kidney. Effects on storage of vitamin A were studied by measuring the concentration of retinyl esters in different organs. The concentrations of retinyl esters in liver, lung and kidney did not significantly differ between transgenic and control mice, and the concentration of total retinol in plasma was within the normal range in transgenic mice. Furthermore, feeding mice a diet with high or low concentrations of vitamin A for 2 wks resulted in no marked differences in the concentrations of retinyl esters in liver, kidney, lung, intestine and testis in transgenic mice compared with control mice. Therefore, in spite of high expression of hCRBP(I) in several organs, the transgenic mice had normal storage of retinyl esters in all organs studied. The present in vivo study indicates that the CRBP(I) content alone does not control retinyl ester storage.
BACKGROUND: The primary purpose of this study was to evaluate concentration-effect relationships of the new steroid anesthetic eltanolone during recovery from a bolus dose and constant rate intravenous infusion in healthy male volunteers. METHODS: Ten subjects received a bolus dose of 0.75 mg/kg eltanolone over 20 s. A 2-h constant rate intravenous infusion of eltanolone was given to five subjects at a rate of 2 mg.kg-1.h-1 and to another five subjects at a rate of 3.5 mg.kg-1.h-1. Recovery performance was assessed as the time required to reach different end-points and by means of three different psychomotor tests. RESULTS: A low interindividual variability was found in the serum concentration of eltanolone at the pharmacodynamic end-points during recovery. The Cp50 value for "eye opening" was 382 micrograms/L (95% confidence interval, 285-489) after a bolus dose corresponding to a median time of 16 min (range 8-25). After eltanolone infusion, the Cp50 value for "eye opening" was 507 micrograms/L (95% confidence interval, 425-605) and the corresponding median time was 21 min (range 8-25) in the low-dose group and 49 min (range 31-66) in the high-dose group. The Cp50 values at the same effect end-points in the bolus group were less than those in the infusion groups, probably because of insufficient equilibration time between serum and the effect compartment. CONCLUSIONS: Recovery characteristics of eltanolone were predictable because of a relatively low interindividual variability in serum concentrations but with a slow blood:effect compartment equilibration.
We studied the association between the operative course of transurethral resection of the prostate (TURP) and the morbidity of acute myocardial infarction (AMI) in a cohort comprising 846 patients who underwent this operation between 1983 and 1992. Up to the end of 1993, a total of 69 patients had developed AMI, of which 10 patients had a reinfarction. The relative risk associated with absorption of 500 ml or more of the irrigating medium during surgery was 1.6 [95% confidence interval (CI) = 0.9-3.0] for a first-time AMI after TURP, 6.1 (95% CI = 1.8-20.7) for a reinfarction, and 2.2 (95% CI = 1.3-3.9) for a first-time or a reinfarction combined. A blood loss of 275 ml or more was associated with a decreased relative risk (RR = 0.4; 95% CI = 0.2-0.8) of a first-time AMI after TURP. Patients who lost less than 275 ml of blood and absorbed 500 ml or more of irrigating fluid during surgery had 4.4 times the risk of having an acute myocardial infarction (RR = 4.4; 95% CI = 1.7-11.8). These results appear to indicate that the operative course of TURP is important to the development of AMI over an extended period of time.
Adult New Zealand rabbits were used to transplant autologously harvested and in vitro cultured chondrocytes into patellar chondral lesions that had been made previously and were 3 mm in diameter, extending down to the calcified zone. Healing of the defects was assessed by gross examination, light microscope, and histological-histochemical scoring at 8, 12, and 52 weeks. Chondrocyte transplantation significantly increased the amount of newly formed repair tissue compared to the found in control knees in which the lesion was solely covered by a periosteal flap. In another experiment, carbon fiber pads seeded with chondrocytes were used as scaffolds, and repair significantly increased at both 12 and 52 weeks compared to knees in which scaffolds without chondrocytes were implanted. The histologic quality scores of the repair tissue were significantly better in all knees in which defects were treated with chondrocytes compared to knees treated with periosteum alone and better at 52 weeks compared to knees in which defects were treated with carbon scaffolds seeded with chondrocytes. The repair tissue, however, tended to incomplete the bonding to adjacent cartilage. This study shows that isolated autologous articular chondrocytes that have been expanded for 2 weeks in vitro can stimulate the healing phase of chondral lesions. A gradual maturation of the hyalinelike repair with a more pronounced columnarization was noted as late as 1 year after surgery.
Therapy with angiotensin II-converting enzyme (ACE) inhibitors has been suggested to prevent cardiovascular hypertrophy in hypertension even in doses that are subantihypertensive. We investigated the effects of two different ACE inhibitors on blood pressure and cardiovascular changes during as well as after discontinuation of treatment in spontaneously hypertensive rats (SHR). SHR were treated with either enalapril (ENA) or ramipril (RAM) from age 12 to age 20 weeks. Each drug was given in either an antihypertensive (ENA 15 mg center dot kg-1, RAM 3 mg center dot kg-1) or a subantihypertensive (ENA 50 mu g center dot kg-1, RAM 10 mu g center dot kg-1) dose. Mean arterial pressure (MAP) was reduced with antihypertensive doses of ENA (26%) as well as RAM (21%). Regression of cardiovascular changes occurred as reduction in left ventricular (LV) weight/body weight ratio (25 and 21% for ENA and RAM, respectively), reduction in perfusion pressure at maximal vasodilation of the perfused hindquarter (PPdil, 17 and 17%), and reduction in maximal developed pressure (PPmax, 13 and 17%). These effects partly persisted 10 weeks after treatment was discontinued. However, treatment with subantihypertensive doses of ENA and RAM had no effect on MAP, LV/body weight ratio, PPdil, or PPmax. Overall, regression of cardiovascular parameters correlated closely to the decrease in MAP. Similarly, no changes in MAP, LV weight/body weight ratio, PPdil, or PPmax were noted when young SHR were treated with subantihypertensive doses of RAM from age 6 to age 12 weeks, during which time hypertension becomes established. At doses having equal effects on blood pressure, plasma concentrations of RAM were considerably lower than those of ENA. Skeletal muscle concentrations were very low or undetectable in comparison to plasma concentrations for both drugs. Therefore, both RAM and ENA caused regression of cardiovascular changes that could be explained by a concomitant reduction in blood pressure. This regression persisted for a considerable time after discontinuation of treatment. On the other hand, no specific antitrophic effects in the absence of blood pressure reduction was evident with either drug. Furthermore, despite substantial differences in plasma concentrations, RAM, and ENA administered chronically appeared to affect cardiovascular parameters equally in the adult SHR.
The aim of this study was to develop a polymerase chain reaction (PCR) method for the detection of pathogenic Yersinia enterocolitica and to compare it with an official culture method (NMKL-117). Primers were selected for nested PCR directed at the attachment invasion locus, ail, on the bacterial chromosome, as well as at a sequence on the pathogenic marker plasmid, termed virulence factor, virF. The final results obtained by the two methods were similar. However, while the conventional method yielded contradictory data for some steps the PCR method provided unambiguous results. Considerable advantages, i.e. higher sensitivity and specificity of the PCR method, compared with the conventional method for detecting pathogenic Y. enterocolitica, were demonstrated in this study.