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Biomedical subjects

J Svedberg

Publications and source records attributed to J Svedberg.

At least 19 recordsLinked to original sources

Cerebrovascular effects of the TRH analogues pGlu-3-methyl-His-Pro amide and pGlu-Glu-Pro amide: a comparison with TRH.

The goal of the study was to assess whether TRH analogues possess cerebrovascular effects similar to the native peptide. The neuropeptide thyrotropin releasing hormone (TRH) elicits cerebrovasodilation in several species under various conditions. The laser-Doppler method was employed to study the effects of TRH and the analogues pGlu-3-methyl-His-Pro amid (M-TRH) and pGlu-Glu-Pro amide. Intravenous (i.v.) injection of 300 microg kg(-1) of TRH elicited cerebrovasodilation and a 62% increase in blood flow within 1 minute. M-TRH, in a dose of 300 microg kg(-1) i.v., elicited a 80% increase in cerebral blood flow. Even a minute dose of M-TRH (625 ng kg(-1)) caused an increase in cerebral blood flow. No clear difference in effects on the cerebral blood flow was observed between spontaneously and mechanically ventilated animals, pGlu-Glu-Pro amide had no cerebrovascular effect.

Animals↗

Effect of rearing factors on the prevalence of floor eggs, cloacal cannibalism and feather pecking in commercial flocks of loose housed laying hens.

1. Effects of rearing conditions on behavioural problems were investigated in a cohort study of commercial flocks of laying hens housed in 2 different loose housing systems. The sample population was 120 385 laying hens from 59 flocks of various hybrids at 21 different farms. 2. Logistic regression modelling was used to test the effects of selected factors on floor eggs, cloacal cannibalism and feather pecking. In addition to early access to perches or litter, models included hybrid, stocking density, group size, housing system, age at delivery, identical housing system at the rearing farm and at the production farm and, in models for floor eggs and cloacal cannibalism, nest area per hen. Odds ratios were calculated from the results of the models to allow risk assessment. 3. No significant correlations were found between the prevalence of floor eggs, cloacal cannibalism and feather pecking. 4. Access to perches from not later than the 4th week of age decreased the prevalence of floor eggs during the period from start-of-lay until 35 weeks of age, odds ratio 0-30 (P<0-001). Furthermore, early access to perches decreased the prevalence of cloacal cannibalism during the production period, odds ratio 0-46 (P=0.03). 5. No other factor had a significant effect in these models. Although it was not significant, early access to litter had a non-significant tendency to reduce the prevalence of feather pecking.

Aggression↗

Wet litter and perches as risk factors for the development of foot pad dermatitis in floor-housed hens.

1. An experiment was conducted to determine whether different moisture levels of litter and perches with different hygienic conditions are involved in the manifestation of foot pad dermatitis in White Leghorn layers. 2. Four different treatments were compared: dry litter and dry perches; dry litter and wet perches; wet litter and dry perches; and wet litter and wet perches. Temperature, pH, air humidity and ammonia changes in the pens were monitored. 3. The mean prevalence of foot pad lesions in groups 1, 2, 3 and 4 was 17%, 13%, 49% and 48% respectively. The overall incidence of foot pad lesions in birds reared on dry litter was 38%, and in birds reared on wet litter 92%. 4. When the air temperature was above 20 degrees C, an increasing moisture content in the litter was associated with an increasing incidence of foot pad dermatitis. However, when the air temperature was below 20 degrees C there were no new cases of dermatitis in any of the 4 treatments. There were no significant differences in litter pH or ammonia between the 4 treatments when compared over the whole experiment. 5. Although the incidence of lesions was not significantly affected by the presence of wet perches, the area of the lesions tended to be in groups with wet patches than in groups with dry perches. 6. It is suggested that moisture and temperature are important contributing factors for the occurrence of foot pad dermatitis in laying hens. Wet perches may contribute to the severity of such lesions.

Animals↗

Rearing conditions and foot-pad dermatitis in Swedish broiler chickens.

A method of classification of broiler foot-health status was developed to estimate the prevalence of foot-pad dermatitis in Swedish broilers. Data on foot health were collected from 101 commercial broiler flocks at slaughter. The producers were asked to fill in a questionnaire on rearing conditions and equipment for every flock. Lesions were commonly observed; only 62% of the birds were classified as being without lesions, 32% had mild lesions only (discoloration, erosions) and 6% had severe lesions (ulcers). Flocks reared in houses equipped with small water cups had significantly (P < 0.05) higher prevalences of foot-pad dermatitis than flocks reared with water nipples. Thick layers of litter, regardless of litter material, also resulted in significantly (P < 0.05) higher prevalences of foot-pad dermatitis than litter layers thinner than 5 cm.

Animal Husbandry↗

Tc-scintimetry in 56 cementless hip arthroplasties. A prospective, randomized comparison of two femoral components.

In a prospective, randomized study of cementless total hip arthroplasties, radionuclide images as well as radiographs were obtained at 6, 12, and 36 months postoperatively. The femoral component was porous-coated, rigid in 28 patients and smooth, isoelastic in 28. The radionuclide uptake was quantified in the regions of interest and correlated to the non-operated side. Among prostheses considered to be stable 3 years after surgery, the activity had normalized in the calcar region. The uptake was also reduced below the tip of the prostheses, but the activity was still 50 percent increased compared to the non-operated side. The isoelastic prosthesis showed less reduction of activity below the tip than the rigid prosthesis. Proximally, the isoelastic prosthesis showed no reduction of activity, whereas the rigid prosthesis had normalized the uptake at the 3-year control. A high rate of non-stable fixation was observed for the flexible prosthesis at the radiographic assessment, which may have contributed to the increased radionuclide activity. Sequential scintimetry may be used as a complement to the radiographic evaluation of the femoral component of the hip prosthesis.

Bone Remodeling↗

Effect of free fatty acids on insulin receptor binding and tyrosine kinase activity in hepatocytes isolated from lean and obese rats.

We demonstrated previously that high physiological concentrations of free fatty acids (FFA) rapidly decrease insulin binding, degradation, and action in isolated rat hepatocytes. In this study, hepatocytes from lean and obese Sprague-Dawley rats (Alab, Stockholm) were preincubated with or without 0.4 mM oleic acid, and the effect on insulin binding and tyrosine kinase activity was measured. In the absence of exogenous FFA, insulin binding was reduced in hepatocytes from obese compared with lean rats (mean +/- SE reduction 44 +/- 7%, n = 8, P less than 0.01). Furthermore, the inhibitory effect of oleic acid added to hepatocytes from lean rats (n = 8; 40 +/- 9%, P less than 0.01) was not seen in cells from obese rats. Treating obese rats with Etomoxir, a carnitine palmitoyl transferase I inhibitor, increased insulin binding to isolated hepatocytes by 41 +/- 13% (n = 5, P less than 0.05). There was no difference in total binding to partially purified insulin receptors from solubilized hepatocytes from lean and obese rats, whether cells were or were not preincubated with oleic acid. Tyrosine kinase activity of partially purified receptors from basal or insulin-stimulated cells was not affected by either obesity, treatment with Etomoxir, or preincubating the cells with oleic acid. Thus, both obesity and elevated ambient FFA levels are associated with impaired insulin cell surface binding to isolated hepatocytes, possibly through an effect of lipid oxidation on the internalization/recycling of the insulin-receptor complex without any perturbation of the receptor tyrosine kinase activity. The data suggest that the reduced insulin binding to hepatocytes from obese rats is due to elevated ambient FFA levels.

Animals↗

Absorption of irrigating fluid during transurethral prostatic resection as measured by ethanol, radioisotopes, and regular-interval monitoring.

Ethanol monitoring is a novel noninvasive method for immediate detection of absorption of irrigating fluid during transurethral prostatic resection. Its accuracy was evaluated during thirteen resections using 5% mannitol +2% ethanol as the irrigating fluid. The ethanol concentration in the expired breath correlated strongly with the degree of absorption of intravascular irrigating fluid as determined by a radioisotope technique, and fluid volume measurements, and with the changes in the serum sodium concentration. Extravascular absorption of the irrigating fluid resulted in prolonged elevation of the ethanol concentration and gave smaller changes in the serum sodium concentration.

Absorption↗

Fatty acids in the portal vein of the rat regulate hepatic insulin clearance.

The effects of FFA on hepatic insulin clearance were studied in the in situ perfused rat liver. Clearance decreased with increasing body weight (age) of the rats. When FFA were added to the perfusate a 40% reduction of hepatic removal of insulin was found over the normal, physiological range (less than 1,000 mumol/liter), less pronounced in heavier rats. When perfusion was started with high concentrations of FFA, inhibition was rapidly reversible, a phenomenon again blunted in heavier rats. In contrast to FFA, different glucose concentrations in the perfusate did not affect the hepatic insulin uptake in the presence of FFA within physiological concentrations. Thus, hepatic clearance of insulin is proportional to rat weight (age) and portal FFA concentrations. Other studies have recently shown that fatty acids inhibit insulin binding, degradation, and function in isolated rat hepatocytes, and that hepatic clearance is inversely dependent on hepatic triglyceride concentrations, both inhibitions reversible by prevention of fatty acid oxidation. It is suggested that the diminished hepatic clearance of insulin in heavier (older) rats is at least partly due to their relative obesity and increased hepatic triglyceride contents. This effect as well as that of portal FFA is probably mediated via fatty acid oxidation in the liver. This mechanism may have implications for the regulation of hepatic metabolism, and peripheral insulin concentrations.

Animals↗

Prevention of inhibitory effect of free fatty acids on insulin binding and action in isolated rat hepatocytes by etomoxir.

We recently demonstrated a marked inhibitory effect of high physiological concentrations of free fatty acids (FFAs) on insulin binding, degradation, and action in isolated rat hepatocytes. To elucidate the mechanism, male rats were treated for 3 days with saline (control) or etomoxir (ethyl 2-[6-(p-chlorophenoxy)hexyl]-glycidate), a prodrug, which in vivo is converted to a specific competitive inhibitor of carnitine palmitoyltransferase, and thus, lipid oxidation. Oleic acid (0.4 mM) reduced both 125-I-labeled insulin binding and insulin-stimulated [14C]aminoisobutyric acid transport approximately 40% in cells from control animals. However, this FFA concentration was without effect in cells from etomoxir-treated animals. Etomoxir increased EC50 for the inhibitory effect of oleic acid on insulin binding approximately threefold. The data indicate that the mitochondrial oxidation of fatty acids may be important for their inhibitory effect on insulin binding and action in isolated rat hepatocytes.

Aminoisobutyric Acids↗

Effects of testosterone on muscle insulin sensitivity and morphology in female rats.

Intact or oophorectomized (OVX) female rats were given moderate doses of testosterone for 12 wk. Insulin-stimulated glucose transport with submaximal insulin concentrations was studied with the euglycemic clamp technique. Glycogen synthesis and 2-deoxy-D-glucose uptake were measured during the clamp in the extensor digitorum longus, white and red portions of the gastrocnemius, and in the soleus muscles by tracer technique. Testosterone treatment resulted in elevations of circulating testosterone, increased plasma insulin concentrations, and a marked decrease in insulin-stimulated glucose transport. In control animals, glycogen synthesis and 2-deoxy-D-glucose transport increased with increasing concentrations of type 1 fibers. Testosterone inhibited glycogen synthesis and 2-deoxy-D-glucose transport to approximately 50% in all muscles except 2-deoxy-D-glucose transport in intact rats. Glycogen synthesis in the liver was not affected. Testosterone administration also resulted in changes in muscle morphology. The relative number of type 1 fibers decreased, whereas type 2 fibers increased. This was most pronounced in red muscles. There was also a decrease in capillary density after testosterone treatment. It was concluded that testosterone administered to female rats is followed by marked insulin resistance. This is correlated to alterations in muscle morphology with fewer type 1 fibers and a lower degree of capillarization, which are both known to be characteristics of insulin-insensitive muscles.

Animals↗

Testosterone treatment of ovariectomized rats: effects on lipolysis regulation in adipocytes.

The effects of testosterone treatment (2 mg every 14 days, for three months) on adipocyte lipolysis of intact (250-300 g body weight) and ovariectomized female rats were studied. Testosterone treatment of intact rats had no effect. Ovariectomy was followed by an increase in fat cell size and a decrease of lipolysis stimulated by isoproterenol, norepinephrine, epinephrine, forskolin, cAMP and isobutylmethylxantine. The number of beta-adrenergic receptors was reduced. There was, however, no change in the antilipolytic effects of UK 14,304 (alpha 2-adrenergic agonist), nicotinic acid, N6-phenylisopropyladenosine or insulin. Testosterone treatment of ovariectomized rats restored the number of beta-adrenoceptors and lipolysis stimulated by cAMP and isobutylmethylxantine, but not lipolysis stimulated by catecholamines and forskolin, suggesting a remaining defect in the catalytic unit of adenylate cyclase. These results indicate that ovariectomy is followed by a profound derangement of the lipolytic pathway at several levels, from beta-adrenoceptors number to the triglyceride lipase activity. This is partially restored by treatment with testosterone, which, however, has no effect on intact female rats. This study emphasizes the importance of ovarian integrity for the lipolytic regulation and the inability of testosterone to replace ovarian function in this regard or to affect lipolysis in intact female rats.

1-Methyl-3-isobutylxanthine↗

Free-fatty acid inhibition of insulin binding, degradation, and action in isolated rat hepatocytes.

The effect of free fatty acids (FFAs) on insulin binding and action was investigated in isolated rat hepatocytes. Oleic acid (0.4 mM) added to the cells rapidly (within 45 min) reduced insulin binding and degradation (each by 45%; P less than 0.001, n = 7) without changing the apparent receptor affinity. The effect was concentration dependent; a half-maximal inhibitory effect occurred at 0.150 +/- 0.050 mM (mean +/- SE). Oleic acid exerted no effect on insulin binding in energy-depleted (KCN-treated) cells. Oleic, palmitic, stearic, palmitoleic, and eicosapentaenoic acids were equally effective in reducing insulin binding. FFA did not change insulin binding to partially purified insulin receptors, thus excluding a direct effect on the insulin receptor. Furthermore, binding to partially purified receptors from solubilized cells pretreated with 0.2 mM oleic acid was not changed, indicating the effect of FFA in intact cells is on the rate of receptor internalization and/or recycling. Concomitant with the effect on insulin binding, oleic acid elicited a concentration-dependent reduction in nonstimulated cellular [14C]aminoisobutyric acid uptake (AIB; 29 +/- 8%, P less than 0.05) and decreased the maximal effect of insulin (39 +/- 7%, P less than 0.05). Thus, in a concentration-dependent manner, different fatty acids can reduce the number of binding sites for insulin and the degradation of insulin by isolated liver cells. Basal and insulin-stimulated AIB transport was reduced, suggesting the presence of postbinding perturbations. These data suggest that FFA exerts an important modulating effect on insulin action in the liver.

Aminoisobutyric Acids↗

Effect of microspheres in intra-arterial chemotherapy. A study of arterio-venous shunting and passage of a labelled marker.

Degradable starch microspheres (DSM) mixed and injected with a cytostatic drug might improve intra-arterial chemotherapy by increasing the local drug concentration. Several factors are of importance for an optimal effect of the microspheres, e.g. size and vascularity of the tumour, arterial blood flow and arterio-venous shunts. Therefore, the dose of DSM has to be individualized. A method for continuous monitoring of the effect of DSM was developed. A radiolabelled marker was injected intra-arterially mixed with DSM and mitomycin C. Two kinetic parameters--Passing Fraction and Marker Flow Rate--were found to be influenced by the microspheres and thus seemed to be useful for monitoring the DSM-treatment. Arterio-venous shunting was measured as passage of 99Tcm-labelled macroaggregated albumin through the liver to the lungs. Significant increase of shunting after injection of DSM was demonstrated in 15 out of 19 patients. Almost no effect of the microspheres was seen in patients with marked arterio-venous shunting or minimal reduction of the marker flow rate, but in others the passage of the labelled marker could generally be significantly reduced.

Adult↗

Intra-arterial mitomycin C treatment of unresectable liver tumours. Preliminary results on the effect of degradable starch microspheres.

Regional chemotherapy might be more efficient if the cytostatic drug is injected together with degradable starch microspheres (DSM), which induce temporary blockage of arterioles and trap the co-injected drug in tumour. Eighteen patients with non-resectable liver cancer were included. Mitomycin C (15 mg/m2) was injected intra-arterially mixed with 900 mg of DSM every six weeks. For estimation of the effect of DSM in the liver a radiolabelled tracer was injected via the same route. Its passage through the liver to the systemic circulation was continuously measured by a detector situated over peripheral blood vessels. The effect of DSM on the tracer passage varied considerably between different patients. The study also indicated opening of new vascular pathways some minutes after the initial injection. The dose of DSM for total blockage of the arterial blood flow, indicated by angiography, also varied. In some patients 540 mg induced total occlusion. In others neither angiographic nor tracer passage were affected by the microspheres although 900 mg (or even more) were injected. Factors such as size of the vascular bed, portal and arterial blood flow and arterio-venous shunting seemed to be of great importance and should be controlled in order to optimize the use of DSM in conjunction with chemotherapy of liver tumours.

Female↗

Effect of portal blood flow and intra-arterially injected starch microspheres on the passage of a labelled tracer through the liver. An experimental study in pigs.

Pig liver was used to study the influence of portal blood flow and degradable starch microspheres (DSM) on the passage of radiolabelled methylene-di-phosphonate from the hepatic artery to the systemic circulation. When the portal vein was clamped abut 70 per cent of the labelled marker injected into the hepatic artery passed to the systemic circulation and the remaining 30 per cent passed when the portal vein was opened. When the flow of the hepatic artery was stopped, the portal blood flow alone drained about 65 per cent of the marker, which was given as a small volume injection into the hepatic artery. When both the arterial perfusion and the portal blood flow were closed the marker only slowly passed to the systemic circulation. DSM injected into the hepatic artery reduced the passage of the marker through the liver to 75 per cent of the reference level when the portal vein was open. When it was clamped this figure was reduced to about 25 per cent. The effect of DSM on the passage of the labelled marker was found to be dose dependent. It is suggested that the reduced passage of a labelled tracer given mixed with DSM is a useful measure of degree of arterial occlusion in the liver. However, because of the drainage via the portal system the passage cannot be completely inhibited.

Animals↗

Enterogastric reflux after gastric surgery. A comparison between gastroduodenostomy and Roux diversion.

Reflux of upper intestinal content to the gastric remnant after gastric resection is common and may cause damage to the gastric mucosa, resulting in gastritis, gastric ulcer, and possibly dysplasia. Different surgical procedures have been proposed to prevent reflux, among them Roux-en-Y diversion. In this study we have compared antrectomy followed by gastroduodenostomy (BI) with antrectomy followed by Roux-en-Y anastomosis with regard to enterogastric reflux. Reflux was recorded by cholescintigraphy, using a new method for quantification. In all patients biopsy specimens were taken for histopathological evaluation at gastroscopy. Twenty-seven patients were studied, 11 with gastroduodenostomy and 16 with Roux-en-Y diversion. All patients in the gastroduodenostomy group had reflux, compared with four in the Roux group (p less than 0.001). Under the light microscope all patients in the BI group showed a moderate to severe degree of inflammation compared with only seven in the Roux-en-Y group (p = 0.028). Our results show that Roux-en-Y drainage effectively diminishes reflux and may be an explanation for the lower extent of mucosal damage in these patients.

Adult↗