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P Sidenius

Publications and source records attributed to P Sidenius.

At least 19 recordsLinked to original sources
PubMed1989

Slow axonal transport of structural polypeptides in rat, early changes in streptozocin diabetes, and effect of insulin treatment.

The synthesis and transport of slowly transported polypeptides in sciatic nerves of rats was investigated by [35S]methionine pulse labeling and gel electrophoresis in control, diabetic, and insulin-treated diabetic rats. To detect very early changes diabetes was induced by streptozocin only 5 days prior to the labeling of the dorsal root ganglion cells. Fourteen days were allowed for axonal transport. In this experimental system, the neurofilament triplet is transported at an apparent velocity of 1.1 +/- 0.1 mm/day (mean +/- SD). The actin-related complex, including actin and two polypeptides of 87 kilodaltons and 37 kilodaltons, was transported at a velocity of 2.6 +/- 0.2 mm/day. For alpha- and beta-tubulin we found an apparent transport velocity of 2.2 +/- 0.1 mm/day, placing it between actin and the neurofilament triplet. The diabetic rats had a selective 32% decrease in the amount of the heaviest neurofilament subunit: 0.47 +/- 0.19% of trichloroacetic acid-insoluble radioactivity versus 0.69 +/- 0.17% in controls; 2p less than 0.05. This decrease was associated with a proximal accumulation of the two lighter neurofilament subunits. Insulin treatment of a diabetic group failed to normalize the changes of axonal transport and additional changes suggesting a hypoglycemic injury was observed.

Actins↗
PubMed1989

Prazosin treatment of neurological patients with detrusor hyperreflexia and bladder emptying disability.

In a placebo-controlled clinical trial with cross-over design the effect of alpha-adrenoceptor blockade with prazosin was studied in 18 neurological patients with detrusor hyperreflexia and bladder emptying disability. During active treatment both the distance to maximal urethral closure pressure (MUCP) and MUCP were significantly reduced. In addition, the volume at first bladder contraction was increased. The urodynamic parameters measured during voiding were unaffected. We conclude that prazosin decreases detrusor hyperreflexia but only in rare cases may benefit bladder emptying in these patients.

Female↗
PubMed1987

Axonal transport of slow component a in sciatic nerves of hypo- and hyperthyroid rats.

Axonal transport of slow component a was studied in dorsal root afferents of the sciatic nerves of hypo- and hyperthyroid rats. Three experimental groups of rats were made hypothyroid at the age of 12 weeks by the administration of 131I. From the age of 22 weeks to the end of the study, the groups were treated with daily subcutaneous injections of thyroxine in various doses to make them hypo-(0 microgram/100 g), normo- (1 microgram/100 g), and hyperthyroid (6 micrograms/100 g), respectively. The hypothyroid group had a moderate thyroid hormone deficiency (a serum triiodothyronine level of 0.19 +/- 0.10 nmol/L and a heart/body weight ratio of 1.87 +/- 0.09 g/kg at time of killing compared with 0.60 +/- 0.09 nmol/L and 2.18 +/- 0.06 g/kg, respectively, for the control group). The hyperthyroid group was severely deranged, with serum triiodothyronine being 3.30 +/- 0.37 nmol/L and a heart/body weight ratio of 3.11 +/- 0.16 g/kg. The hypothyroid rats showed a reduction in mean velocity for the transport of slow component a (0.80 +/- 0.07 mm/day compared with 0.91 +/- 0.05 mm/day in the controls). The width of the wave of activity was smaller for the hyperthyroid group than for the control group (6.6 +/- 0.7 mm compared with 8.1 +/- 1.2 mm), suggesting an increased clearance of the axonally transported activity in the proximal axon. A decrease in transport of slow component a in hypothyroidism may be the explanation of peripheral neuropathy with axonal degeneration occasionally seen in patients with severe myxoedema.

Animals↗
PubMed1987

Quantitative changes of cerebral neocortical structure in insulin-treated long-term streptozocin-induced diabetes in rats.

The brains of rats with streptozocin-induced diabetes treated with a low-dose insulin regimen (1 IU/day) were studied with morphometric techniques. After 1 yr of diabetes, brain weight decreased slightly (1350 +/- 71 vs. 1521 +/- 55 mg, 2P less than .01) as did the volume of the neocortex (498 +/- 36 vs. 567 +/- 40 mm3, 2P less than .05). A significant loss of neocortical neurons occurred (38 +/- 2 X 10(6) vs. 46 +/- 3 X 10(6), 2P less than .01), and the length of the capillary network in the neocortical tissue shortened disproportionately (405 +/- 102 vs. 631 +/- 47 m, 2P less than .01), leading to increased diffusion distance. The mechanisms underlying cerebral loss in this model are unknown, but abnormalities of the vascular supply with prolongation of the route of diffusion might play a role.

Animals↗
PubMed1987

Diabetes decreases Na+-K+ pump concentration in skeletal muscles, heart ventricular muscle, and peripheral nerves of rat.

Na+-K+-ATPase or the Na+-K+ pump is essential for some specific properties of muscle and nerve tissue such as contractility and excitability. Previous studies have shown conflicting variations in Na+-K+-ATPase activity or Na+-K+ pump concentration of muscle cells in experimental diabetes. Our study demonstrates that early untreated diabetes in rats induced by injection of streptozocin is associated with decreases in [3H]ouabain binding-site concentration of 24-48% in various skeletal muscles and 16% in peripheral nerves as well as a decrease in K+-dependent 3-O-methylfluorescein phosphatase activity of 21% in the heart ventricle. These effects could be prevented by insulin treatment. They probably represent a decrease in the concentration of Na+-K+ pumps. There was no evidence for more than one population of Na+-K+ pumps in intact samples of skeletal muscle and nerves from normal, diabetic, and insulin-treated animals. The decrease in Na+-K+ pump concentration in nerve cells may be due to atrophy of the axons. In skeletal muscles, myocardium, and peripheral nerves, the observed decrease in Na+-K+ pump concentration may be important for the pathophysiology of diabetes. We emphasize that quantification of Na+-K+-ATPase or the Na+-K+ pump in muscle and nerve tissue from diabetic animals should preferably be performed with either intact samples or crude homogenates of whole tissue.

Animals↗
PubMed1987

Anterograde fast component of axonal transport during insulin-induced hypoglycemia in nondiabetic and diabetic rats.

To elucidate the pathogenesis of the peripheral neuropathy associated with hypoglycemia the anterograde fast component (aFC) of axonal transport was studied in nondiabetic rats during acute and prolonged insulin-induced hypoglycemia and in streptozocin-diabetic (STZ-D) rats with acute hypoglycemia. [35S]methionine and [3H]fucose were injected into the dorsal root ganglion (L5) to label protein and glycoprotein, respectively. During the 4 h of transport, thigh temperature was maintained constant. Acute severe hypoglycemia (1.5 +/- 0.2 mM) was associated with a 36% decrease in the amount of aFC (2.3 +/- 0.7% in the test group vs. 3.6 +/- 0.8% in the controls), whereas transport velocity was unaffected. Prolonged hypoglycemia, obtained by pretreatment with insulin for 3 days, prevented the decrease in amount of aFC. In STZ-D rats, acute severe hypoglycemia (1.5 +/- 0.6 mM) produced a similar but less-pronounced decrease of aFC. We conclude that hypoglycemia is associated with alterations in axonal transport that could play a role in development of neuropathy. Prolonged hypoglycemia protects axonal transport against the effects of glucopenia, and an untreated diabetic state maintained for several days has a partially protective effect against episodes of hypoglycemia.

Animals↗
PubMed1986

The retrograde fast component of axonal transport in motor and sensory nerves of the rat during administration of 2,5-hexanedione.

The retrograde and anterograde fast component of axonal transport (rFC and aFC) were examined in rats following intoxication with 2,5-hexanedione (1 g/kg/week) for 2, 4, 6 and 8 weeks. rFC and aFC were measured as accumulations distal and proximal to a double ligature after labeling of protein by injection of [35S]methionine into L5 spinal cord or L5 dorsal root ganglion. Clinical symptoms appeared after an accumulated dose of 6 g/kg of the toxin and was dominated by motor deficiencies. Abnormalities in retrograde build-up appeared earliest in motor nerves after an accumulated dose of 4 g/kg, while the sensory nerves showed a decreased retrograde build-up only after 6 g/kg. In motor nerves retrograde build-up for the short and the long accumulation interval (11.5-17.5 h and 11.5-25.5 h, respectively) was equally depressed, while in sensory nerves the retrograde build-up for the early accumulation interval (10-16 h) was less severely depressed as compared to the late collection interval (10-24 h). These findings point to a decreased amount of rFC, rather than a delay in turn-around. Furthermore, build-up was inversely correlated with the dose of 2,5-hexanedione and was most pronounced in motor nerves (82% vs 52% in motor and sensory nerves, respectively) at the final dose of 8 g/kg. When intoxication was stopped, rats improved in muscle-strength, but still showed atrophy of leg muscles. Coincidently, retrograde transport in motor nerves was normalized for the short accumulation interval, and improved for the longer collection interval, though not completely normalized.

Animals↗
PubMed1986

The effect of doxorubicin on slow and fast components of the axonal transport system in rats.

The study was designed to investigate the changes in axonal transport that result from disturbances in protein synthesis. Doxorubicin, an antineoplastic drug which interferes with the function of DNA, has a selective effect on peripheral sensory nerves because of the high vascular permeability in the dorsal root ganglia. After the intravenous administration of a moderate dose (4 mg/kg) to male Wistar rats, the transport of slow component a (SCa) was found to be retarded, transport velocity being decreased by 17% (0.85 +/- 0.06 mm/day vs 1.03 +/- 0.06 mm/day in controls). The transport kinetics of the fast anterograde and retrograde components (aFC and rFC) were unchanged after the administration of a dose of 6 mg/kg, although the relative amount of aFC was decreased by 27% (3.2 +/- 0.9% vs 4.4 +/- 1.1% in controls). It is suggested that the neuronopathy induced by doxorubicin is mediated by changes in axonal transport.

Animals↗
PubMed1986

Anterograde components of axonal transport in motor and sensory nerves in experimental 2,5-hexanedione neuropathy.

Anterograde slow and fast axonal transport was examined in rats intoxicated with 2,5-hexanedione (1 g/kg/week) for 8 weeks. Distribution of radioactivity was measured in 3-mm segments of the sciatic nerve after labelling of proteins with [35S]methionine or [3H]leucine and glycoproteins with [3H]fucose. The axonal transport of the anterograde slow components was examined after 25 (SCa) and 10 days (SCb), in motor and sensory nerves. SCa showed an increased transport velocity in motor (1.25 +/- 0.08 mm/day versus 1.01 +/- 0.05 mm/day) and in sensory nerves (1.21 +/- 0.13 mm/day versus 1.06 +/- 0.07 mm/day). The relative amount of labelled protein in the SCa wave in both fiber systems was also increased. SCb showed unchanged transport velocity in motor as well as in sensory nerves, whereas the amount of label was decreased in the motor system. Anterograde fast transport in motor nerves was examined after intervals of 3 and 5 h, whereas intervals of 2 and 4 h were used for sensory nerves. Velocities and amounts of labelled proteins of the anterograde fast component remained normal. We suggest that the increase in protein transport in SCa reflects axonal regeneration.

Animals↗
PubMed1986

A proposal for a classification of neuropathies according to their axonal transport abnormalities.

Recent studies on axonal transport in experimental neuropathy are reviewed and the following combinations of pathological changes and underlying axonal transport abnormalities are proposed for a classification of polyneuropathies. Alterations of the anterograde transport of slow component a(SCa) leads to changes of the dimensions of the axon calibre without the occurrence either of overt neuropathy or fibre loss. Thus damming of SCa in beta,beta'-iminodiproprionitrile (IDPN) intoxication results in axonal swelling in nerve roots whereas decrease of SCa leads to atrophy distal to the swellings in IDPN intoxication and in streptozotocin induced diabetes as well. Decrease in the amount of material conveyed within the anterograde fast component (aFC) leads to acute axonal degeneration including break down of axons and fibre loss. This state occurs in acute hypoglycaemia and in doxorubicin intoxication. The most frequent type of polyneuropathy, namely distal axonopathy with accumulation of axon organelles leading to distal fibre loss, is associated with decrease in amount of the retrograde fast component (rFC). The transport is impaired before the appearance of symptoms and electrophysiological signs of neuropathy develop in the intoxications induced by parabromophenylacetylurea, acrylamide and 2.5 hexanedione, and the severity of neuropathy is proportional to the rFC impairment.

Animals↗
PubMed1986

Slow component-a of axonal transport, nerve myo-inositol, and aldose reductase inhibition in streptozocin-diabetic rats.

This study measured sugars and polyols, weight/unit length, and slow component-a of axonal transport (SCa) in dorsal root afferents of the sciatic nerves of control rats and rats with streptozocin (STZ)-induced diabetes of 4-wk duration. The effects of two treatments--aldose reductase inhibition [Statil ("Statil" is a trademark; the property of Imperial Chemical Industries PLC.) ICI 128436 at 25 mg/kg/day, p.o.] and myo-inositol supplementation (650 mg/kg/day, p.o.)--were studied in control and diabetic groups. Inclusion of untreated controls and diabetics gave a total of six groups for the study. The treatments were begun on the day after injection of STZ and were maintained throughout the protocol. The sciatic nerves of the diabetic (untreated) rats showed accumulation of sorbitol and fructose, depletion of myo-inositol, and an 8% increase in weight/unit length. All of these abnormalities were prevented by treatment with Statil. Treatment of diabetic rats with myo-inositol prevented its depletion in the sciatic nerve, but did not affect the accumulation of sorbitol and fructose nor the increase in weight/unit length. Neither treatment exerted any apparent effect on body weight, blood glucose, nerve weight, or nerve sugars and polyols in the control rats. The diabetic rats showed a retardation of the wave of transported-labeled protein (shown as increased leftward skewness of the wave) and a reduction in mean transport velocity (calculated as the mean velocity for all segments contributing to the transport wave: 0.96 +/- 0.09 mm/day in diabetics versus 1.15 +/- 0.07 mm/day in controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1983

Axonal transport in neuropathy.

Recent studies on the distribution of labeled endogenous proteins in the experimental neuropathies induced by streoptozotocin diabetes, galactose feeding, zinc pyridinethione, 2,5-hexanedione, acrylamide, and p-bromophenylacetylurea (BPAU) have demonstrated an impaired build up of retrogradely transported material derived from the more distal parts of peripheral nerve. In BPAU neuropathy the transport abnormality is strongly related to the degree of muscle weakness; following treatment with acrylamide the extent of the impairment is dose related. In both toxic conditions the transport abnormality is present well in advance of the first clinical signs of neuropathy. We therefore suggest that changes in retrograde axonal transport play an initial and important role in the development of many axonopathies.

Acrylamide↗
PubMed1983

Early and dose-dependent decrease of retrograde axonal transport in acrylamide-intoxicated rats.

The effect of retrograde axonal transport of doses of acrylamide ranging from 50 to 500 mg/kg was studied in sensory nerve of rats. Accumulation of trichloroacetic acid-phosphotungstic acid-insoluble label was measured in a collection segment distal to a double ligature placed on the sciatic nerve at intervals 9-15 h and 9-24 h following injection into the dorsal root ganglion of the fifth lumbar root of [35S]methionine and [3H]fucose. After a dose of 100 mg/kg of acrylamide no neurological signs of neuropathy had yet appeared, but retrograde buildup of protein label was significantly reduced for the long interval (2.20 +/- 0.49 arbitrary units (AU) (mean +/- SD) versus 2.81 +/- 0.57 AU in controls, 2p = 0.034). No abnormality of the short interval appeared before a dose of 500 mg/kg was reached. The retrograde transport abnormality was dose-related (r = -0.85, n = 28, and 2p = 1.2 x 10(-8)), as was the degree of neuropathy evaluated by "blind" neurological scoring (r = 0.88, n = 14, and 2p = 2.8 x 10(-5)). After a dose of 500 mg/kg, when the rats were severely disabled with almost total incoordination of the hindlegs, the retrograde accumulation of the long interval was profoundly depressed (1.08 +/- 0.28 AU versus 2.81 +/- 0.57 AU in controls, 2p = 1.2 x 10(-7)). Similar changes were seen in accumulation of glycoprotein label. After the rats had recovered for 4-10 weeks neurological signs of neuropathy had disappeared and the transport abnormality had improved. To test the specificity of acrylamide on the retrograde transport defect N-hydroxymethylacrylamide and methylene-bisacrylamide, which do not induce neuropathy, were studied. None of these related compounds influenced the transport. These observations imply that in acrylamide intoxication a defect in the amount of material carried by retrograde axonal transport rather than in "turnaround" time or in transport velocity is present, that the transport abnormality precedes the development of neuropathy, and that it is related to the degree of the neurological disability. We suggest that the retention of protein in the distal axons in the functional counterpart of the well-known accumulation of vesicular organelles in the preterminals.

Acrylamide↗
PubMed1983

Peripheral neuropathy in rats induced by insulin treatment.

The effect of sustained insulin-induced hypoglycemia on peripheral nerve function and structure was examined in rats. After a period of hypoglycemia (less than 2.5 mmol/L) of at least 72 h, axonal degeneration and reduction of the maximal amplitude of the evoked muscle action potential occurred, the two abnormalities being correlated negatively (r = -0.99, 2P = 0.00097). One of five rats developed paresis of both hindlegs as well as nerve damage and perikaryal alterations of lower motor neurons.

Animals↗
PubMed1982

Change in mast cell dimensions increases the profile number in sections of peripheral nerve of diabetic rats.

Mast cell proliferation has been reported in peripheral nerves of streptozotocin diabetic rats. We examined the question by light microscopy using morphometric techniques including estimation of shape and size. After 4 weeks of diabetes the mast cell area in transverse sections was 32.7 +/- 7.0 microns 2 vs. 22.5 +/- 5.4 microns 2 in controls (P less than 10(2)). Mast cell profiles approximated to ellipses in longitudinal sections, the long diameter being 11.4 +/- 1.2 microns vs. 14.0 +/- 1.0 microns in controls (P less than 10(4)). Correspondingly, the profile number was increased (30 +/- 6%) in longitudinal sections and decreased in transverse sections (11 +/- 16%). The present study does not provide evidence for mast cell proliferation in peripheral nerves in experimental diabetes, and, furthermore, underlines the need of evaluation of dimensions in studies of particle numbers.

Animals↗