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Biomedical subjects

S Christensen

Publications and source records attributed to S Christensen.

At least 163 records · Page 9Linked to original sources

Removal of haem from lipids extracted from intact erythrocytes with particular reference to polyphosphoinositides.

With the use of a modified acid version of a current lipid-extraction technique [Bligh & Dyer (1959) Can. J. Biochem. Physiol. 37, 911-917], 92% of phosphatidylinositol 4,5-bisphosphate obtained by means of three sequential extractions from intact human erythrocytes was obtained during the first one. Some 95% of the haem co-extracted with the lipids could then be removed, with a maximal loss of polyphosphoinositides of less than 3%. About 58 nmol of phosphatidylinositol 4,5-bisphosphate was found per ml of erythrocytes.

Erythrocytes↗

Dihydroergotamine and mobilization after major orthopedic surgery.

The effects of dihydroergotamine (DHE) on the degree of mobilization and response to orthostatic stress after total hip arthroplasty were studied. In the mobilization study, 78 patients received DHE, 0.5 mg im, twice a day from the day of surgery until full mobilization was achieved. Eighty-four patients who received placebo served as controls. There was no significant difference in the time until the first day of mobilization or the degree of mobilization. In the orthostatic test condition, subgroups of 61 patients receiving placebo and 55 patients receiving DHE were subjected to orthostatic testing. There were no differences in cardiovascular response to bed rest or in orthostatic stress. We conclude that DHE does not stabilize the cardiovascular reaction to orthostatic stress, nor does it enhance mobilization in patients after total hip arthroplasty.

Aged↗

Lithium-induced uraemia in rats: survival and renal function and morphology after one year.

Chronic renal failure was induced in Wistar rats by administration of a LiCl-containing (40 mmol/kg) diet from birth until an age of 55-65 weeks. The 55 weeks mortality was 51% in Li-uraemic rats versus 6% in control rats. In surviving rats the mean plasma Li levels were 0.6-0.7 mmol/l after 16 weeks and 1.0-1.1 mmol/l after 48 weeks. The mean plasma urea level was 14 mmol/l after 16 weeks and 22 mmol/l after 48 weeks of treatment compared with 8 mmol/l in the controls rats. In 55 weeks old Li-uraemic rats inulin clearance was reduced by 62% and Li clearance by 39%. Thus, fractional Li excretion was increased (from 20 to 34%) in rats with chronic Li-uraemia. Li-uraemic rats also had polyuria and failed to concentrate their urine in response to exogenous vasopressin. Systolic and mean arterial blood pressures were not significantly changed in rats with Li-uraemia. Morphological examinations of the kidneys showed large cortical cysts formed by dilated distal tubules and collecting ducts and widespread interstitial fibrosis. Proximal tubular mass was reduced by 50% and glomerular volume was also significantly reduced. The results indicate that in rats with Li-induced uraemia renal function and morphology deteriorate during Li-exposure up to an age of one year, associated with increased mortality.

Animals↗

Interstitial focal fibrosis and reduction in proximal tubular length in adult rats after lithium treatment.

Seven adult male and eight adult female rats were treated with lithium for 16 weeks. The kidneys were fixed by vascular perfusion with glutaraldehyde and investigated by morphometric methods. Plasma lithium was in the therapeutic range. All treated animals showed a significant increase in interstitial volume as a result of focal interstitial fibrosis (from 6.6% to 9.8% in males and from 5.2% to 8.4% in females) and a significant reduction in proximal tubular length in male rats (from 292 to 181 m/kidney). Two rats had elevated plasma urea at the end of the experiment. A few animals that were treated for 8 months showed even more significant structural changes. The findings in the present study demonstrate that lithium treatment also in the adult rat leads to focal interstitial fibrosis in the renal cortex.

Animals↗

Tubular sites of furosemide natriuresis in volume-replaced and volume-depleted conscious rats.

There is accumulating evidence that the renal Li clearance reflects the delivery of Na and volume out of the proximal tubules. In the present study we used the Li clearance technique to evaluate the effects of submaximal furosemide (Fur) infusion (7.5 mg/kg/hr) on proximal and distal Na reabsorption in conscious rats with and without volume replacement with saline. Li was given as an p.o. test dose (0.5 mmol/kg) and [3H]inulin was infused in saline to measure the glomerular filtration rate (GFR). In control rats not infused with F, fractional Na excretion was about 1% and fractional Li excretion was about 30 to 35%. Infusion of F with constant rate and volume replacement increased fractional Na excretion to 22% and fractional Li excretion to 57% associated with a small decrease of the GFR. Without volume replacement F infusion caused a smaller and temporary diuretic and natriuretic response (maximum fractional Na excretion = 7.5%) followed by a decrease of urine flow and Na excretion almost to control levels, despite continued high excretion rates of F. The GFR decreased by 25% and fractional Li excretion showed an initial increase followed by return to baseline levels. The results suggest that in conscious rats submaximal doses of F cause major inhibition of proximal tubular Na reabsorption, which effect contributes substantially to the initial natriuresis. Along with diuretic-induced volume contraction, the natriuretic response is abolished due to a fall in GFR and particularly due to a secondary increase in fractional Na reabsorption, which occurs both in proximal distal tubular nephron segments.

Animals↗

Chlorpromazine increases the lowered response to antidiuretic hormone in rats with lithium-induced diabetes insipidus.

The interaction between chlorpromazine (CPZ) and lithium on renal concentrating ability was studied in rats fed a Li-containing diet for 8 weeks (plasma-Li 0.6-0.7 mmol/l). CPZ (15 mg/kg daily orally) reduced the polydipsia and increased the ability to concentrate the urine upon water deprivation in rats treated with lithium. CPZ also reduced systolic blood pressure, but had no effect on the glomerular filtration rate or plasma levels of arginine vasopressin (AVP) in hydrated rats treated with lithium. However, CPZ prevented the rise in plasma AVP levels observed in lithium-polyuric rats in response to dehydration. During anaesthesia CPZ partially restored the impaired anti-diuretic response to exogenous AVP in rats treated with lithium. CPZ had no influence on plasma-Li levels in rats treated with lithium. It is suggested that CPZ by unknown mechanisms interferes with the effects of lithium on the water permeability response to AVP.

Animals↗

Myocardial changes in rats with lithium-induced uraemia.

The possible effects of lithium on myocardial morphology were studied at the light-microscopic level in three different rat models: (i) rats with chronic renal failure due to lithium administration for 8-16 weeks after birth, (ii) normal, adult rats treated with lithium for 16 weeks, and (iii) new-born rats exposed to lithium in their prenatal life. Morphological changes were found in 57% of the male rats with lithium-induced uraemia after lithium administration for 16 weeks postnatally. The changes comprised myocytic degeneration and necrosis associated with infiltration of lymphocytes, histiocytes and plasma cells. This morphological picture is different from the myocardial changes associated with chronic renal failure. Male rats with chronic uraemia after withdrawal of lithium 8 weeks postnatally showed no myocardial changes after 16 weeks. Also, male rats with normal renal function had no myocardial changes after 16 weeks on lithium, but these rats had a significantly lower plasma level of lithium than the lithium-uraemic rats (0.8 vs. 1.4 mmol/l). It is suggested that myocarditis was a consequence of persistent high plasma levels of lithium maintained in the lithium-uraemic rats and that cardiotoxic effects of lithium may be potentiated by concomitant renal failure.

Animals↗

Effects of calcium on the vasopressin-sensitive cAMP metabolism in medullary tubules.

The modulatory effect of Ca on [Arg8]vasopressin-dependent (AVP) cAMP metabolism was studied in medullary collecting tubules (MCT) and medullary ascending limbs (MAL) microdissected from rat kidney. In MCT segments incubated in vitro with AVP, the accumulation of cAMP was enhanced (delta +59%) when Ca was omitted from the incubation medium compared with a medium with 2 mM of ionized calcium (Ca2+). Ionophore A23187 caused a decrease in AVP-stimulated cAMP accumulation in MCT in the presence of 2 mM Ca2+ but not in a Ca2+-free medium. Diltiazem and verapamil enhanced the AVP-stimulated cAMP accumulation in MCT; PTH had no detectable effect. A23187 caused a dose-dependent inhibition of cAMP accumulation stimulated by AVP with forskolin in both MCT and in MAL. However, in MAL the A23187 concentration needed for half-maximum inhibition (6.3 X 10(-6) M) was higher than for MCT (3.9 X 10(-7) M). The maximum inhibition in MAL (-65%) was less than in MCT (-97%). In the presence of 3-isobutyl-1-methylxanthine, AVP-stimulated cAMP accumulation was inhibited by A23187 in MCT (-45%) but not in MAL. Naproxen or ibuprofen did not relieve the inhibitory action of A23187 in MCT. Added Ca2+ inhibited the AVP-stimulated adenylate cyclase in MCT and MAL (half-maximum approximately equal to 5 X 10(-4) M Ca2+) and stimulated cAMP phosphodiesterase (cAMP-PDIE) in both MCT and in MAL (half-maximum approximately equal to 9 X 10(-5) M Ca2+). Incubation of MCT and MAL with A23187 decreased (-50%) the content of ATP. Results suggest that increased influx of extracellular Ca2+ inhibits the AVP-stimulated cAMP accumulation in MCT and to a much lesser degree in MAL. Deceased cAMP accumulation in MCT is probably due to both stimulation of cAMP-PDIE and the inhibition of adenylate cyclase, whereas in MAL it is due to stimulation of cAMP-PDIE. The results suggest that Ca2+ influx exhibits a negative modulatory effect on AVP-dependent cAMP metabolism mainly in MCT.

1-Methyl-3-isobutylxanthine↗

Correlation between distal nephron enzyme activity, structure and function in rats during lithium and lithium plus neuroleptic treatment.

The histochemical activities of nonspecific acid and alkaline phosphatases, NADH- and NADPH-tetrazolium reductases, alpha-glycerophosphate dehydrogenase, succinate dehydrogenase, isocitrate dehydrogenase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase were investigated in kidneys from rats treated with lithium and lithium plus neuroleptics. During the first 8 weeks of lithium treatment the activity of NADH-tetrazolium reductase, succinate dehydrogenase and alpha-glycerophosphate dehydrogenase activity in the collecting ducts increased. The other enzymes did not change. After 8 weeks of treatment no further changes in enzyme activity occurred. Withdrawal of lithium caused normalization of enzyme activity after 8 weeks. A decrease in concentration ability was found in parallel with the increase in enzyme activities (p less than 0.001). The changes in enzyme activity were not significantly correlated to morphological changes in the collecting ducts. Treatment with neuroleptics alone caused no change in enzyme activity. During combined lithium plus neuroleptic treatment the enzyme activities changed in a similar way as during lithium therapy, but the changes were less pronounced. In parallel, a less pronounced decrease in concentration ability was found during this treatment.

Animals↗

Pathogenesis of nephrogenic diabetes insipidus due to chronic administration of lithium in rats.

A polyuric syndrome with nephrogenic diabetes insipidus (NDI) is a frequent consequence of prolonged administration of lithium (Li) salts. Studies in the past, mainly the acute and in vitro experiments, indicated that Li ions can inhibit hydroosmotic effect of [8-arginine]vasopressin (AVP) at the step of cAMP generation in vitro. However, the pathogenesis of the NDI due to chronic oral administration of low therapeutic doses of Li salts is not yet clarified. We conducted a comprehensive study to clarify the mechanism by which Li administered orally for several weeks induces polyuria and NDI in rats. Albino rats consuming a diet which contained Li (60 mmol/kg) for 4 wk developed marked polyuria and polydipsia; at the end of 4 wk the plasma Li was 0.7 +/- 0.09 mM (mean +/- SEM; n = 36). Li-treated rats had a significantly decreased (-33%) tissue osmolality in papilla and greatly reduced cortico-papillary gradient of urea (cortex--43%; medulla--64%; papilla--74%). Plasma urea was significantly (P less than 0.001) lower in Li-treated rats (5.4 +/- 0.2 mM) compared with controls (6.8 +/- 0.3 mM). Medullary collecting tubules (MCT) and papillary collecting ducts (PCD) microdissected from Li-treated animals had higher content of protein than MCT and PCD from the control rats. The cAMP accumulation in response to AVP added in vitro was significantly (delta = -60%) reduced. Also, the cAMP accumulation in MCT and PCD after incubation with forskolin was markedly lower in Li-treated rats. Addition of 0.5 mM 1-methyl,3-isobutyl-xanthine did not restore the cAMP accumulation in response to AVP and forskolin in MCT from Li-treated animals. In collecting tubule segments from polyuric rats with hypothalamic diabetes insipidus (Brattleboro homozygotes) the AVP-dependent cAMP accumulation was not diminished. The activity of adenylate cyclase (AdC) in MCT of Li-treated rats, both the basal and the activity stimulated by AVP, forskolin, or fluoride, was significantly (delta approximately equal to -30%) reduced, while the activity of cAMP phosphodiesterase (cAMP-PDIE) in the same segment showed no significant difference from the controls. Also, the content of ATP in MCT microdissected from Li-treated rats and incubated in vitro did not differ from controls. The rate of [14C]succinate oxidation to 14CO2 in MAL was inhibited (-77%) by 1 mM furosemide, which indicates that this metabolic process is coupled with NaCl cotransport in MAL. The rate of (14)CO(2) production from [14C]succinate in MAL was not significantly different between control and Li-treated rats. In MCT of control rats, the rate of [14C]succinate oxidation was approximately 3 times lower than in MAL. The rate of (14)CO(2) production from [(14)C]succinate in MCT of Li-treated rats was significantly (delta +33%) higher than in MCT dissected from control rats. Based on these results, we conclude that at least two factors play an important role in the pathogenesis of NDI consequent to chronic oral administration of Li: (a) decreased ability of MCT and PCD to generate and accumulate cAMP in response to stimulation by AVP; this defect is primarily due to diminished activity of AdC in these tubular segments caused by prolonged exposure to Li; and (b) lower osmolality of renal papillary tissue, due to primarily to depletion of urea, which decreases osmotic driving force for water reabsorption in collecting tubules. On the other hand, NaCI reabsorption in MAL is apparently not affected by chronic Li treatment.

3',5'-Cyclic-AMP Phosphodiesterases↗

The influence of jejunoileal ratio on plasma electrolytes and liver function in intestinal bypass for morbid obesity. A randomized trial.

In a randomized clinical trial 89 obese patients had end-to-side jejunoileostomy with either a 1:3 or a 3:1 ratio between jejunum and ileum left in continuity. The duration of postoperative observation was at least 36 months. Repeated assessments were made on plasma concentrations of sodium, potassium, bicarbonate, magnesium, calcium, aspartate aminotransferase, and clotting factors. The major findings were that bypass surgery (i) has no important influence on levels of sodium, bicarbonate, and calcium, (ii) induces potassium depletion and transient liver dysfunction of a degree that is independent of the jejunoileal ratio, and (iii) induces a greater magnesium depletion when a long jejunum and short ileum segment are left in continuity.

Clinical Trials as Topic↗

"Handedness" of spiral fractures of the tibia.

"Handedness" is a basic property of spirals. In many cases it is possible to determine whether spiral fractures are right or left handed by analysis of radiographs. Spiral fractures of the tibia show striking bilateral symmetry, with right-handed spirals predominating on the left side of the body, and left-handed spirals on the right.

Humans↗

Occupational accidents and alcohol.

Alcoholic intoxication is commonly considered to be an important cause of occupational accidents. Over a period of one year the alcohol concentration in the breath and/or blood was studied in 5439 patients, who, following an occupational accident, attended the emergency departments of a large Danish provincial city. It is concluded that only a few, apparently less than 3%, were inebriated in the legal sense of the term (BAC above 0.8%) at the time of the accident.

Accidents, Occupational↗