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Biomedical subjects

K G Hedström

Publications and source records attributed to K G Hedström.

At least 19 recordsLinked to original sources

Functional recovery in primates with brachial plexus injury after spinal cord implantation of avulsed ventral roots.

Intraspinal replantation of avulsed spinal nerve roots as a surgical treatment for motor deficits after severe brachial plexus injury was investigated in primates. Under general anaesthesia hemi-laminectomy was performed in cynomolgus monkeys (Macaca fascicularis). Ventral roots within the brachial plexus were then avulsed by traction and subsequently implanted into the ventrolateral aspect of the spinal cord. No dysfunction in the long fibre tracts was seen following surgery. Postoperatively there was a flaccid paralysis of the arm on the lesioned side. Severe atrophy developed within 5-7 weeks in the muscles supplied by the avulsed roots and EMG revealed denervation activity. Two to three months after surgery there were EMG signs of reinnervation, which were shortly followed by evidence of clinical recovery. A gradual improvement in the function of the affected arm occurred and the animals' motor behaviour normalised. One year after surgery there was a full range of motion in the arm, but the EMG activity in the reinnervated muscles at maximal force was reduced. Tracing of regenerated motor neurons with horseradish peroxidase (HRP) injected into the biceps muscle revealed retrogradely labelled motor neurons confined to the ipsilateral ventral horn. It was concluded that intraspinal replantation of avulsed ventral roots in primates significantly promotes motor recovery in the muscles supplied by the lesioned spinal cord segments.

Animals↗

Receptor alterations in manganese intoxicated monkeys.

The density of four different receptors and one marker of dopamine uptake sites were analyzed in monkey brains after manganese exposure (0.1 g manganese per month during 26 months, a dose comparable to that workers might inhale in dusty environments) by means of quantitative receptor autoradiography. The binding of 3H-mazindol to the dopamine uptake sites was reduced by 75% in both the head of the caudate nucleus and putamen, while it remained unchanged in the other regions analyzed. The binding of the D1 receptor ligand 3H-SCH 23,390 was reduced about 45% in the same areas as mazindol binding, while the density of D2 receptors was unaffected. The muscarinic acetylcholine receptors as well as GABAA receptors remained also unchanged in all brain areas analyzed after manganese exposure. Thus the dopaminergic neurons must be considered to be vulnerable to manganese concentrations attainable in the work environment. Our results also indicate that postsynaptic structures containing D1 receptors are sensitive while cells containing D2 receptors are either spared or compensated for by up-regulation of the number of receptors on remaining sites.

Animals↗

Manganese induced brain lesions in Macaca fascicularis as revealed by positron emission tomography and magnetic resonance imaging.

A series of positron emission tomography scans was made on two monkeys during a 16-month period when they received manganese(IV)oxide by subcutaneous injection. The distribution of [11C]-nomifensine uptake, indicating dopamine terminals, was followed in both monkey brains. The brain distributions of [11C]-raclopride, demonstrating D2 dopamine receptors, and [11C]-L-dopa, as a marker of dopamine turnover, were followed in one monkey each. The monkeys developed signs of poisoning namely unsteady gait and hypoactivity. The [11C]-nomifensine uptake in the striatum was reduced with time and reached a 60% reduction after 16 months exposure. This supports the suggestion that dopaminergic nerve endings degenerate during manganese intoxication. The [11C]-L-dopa decarboxylation was not significantly altered indicating a sparing of [11C]-L-dopa decarboxylation during manganese poisoning. A transient decrease of [11C]-raclopride binding occurred but at the end of the study D2-receptor binding had returned to starting values. The magnetic resonance imaging (MRI) revealed that the manganese accumulated in the globus pallidus, putamen and caudate nucleus. There were also suggestions of gliosis/edema in the posterior limb of the internal capsule. MRI might be useful to follow manganese intoxication in humans as long as the scan is made within a few months of exposure to manganese, i.e. before a reversal of the manganese accumulation.

Animals↗

Immunizations of monkeys with synthetic peptides disclose conserved areas on gp120 of human immunodeficiency virus type 1 associated with cross-neutralizing antibodies and T-cell recognition.

Site-directed immunization was employed to identify sites on the envelope glycoprotein gp120 for antibody-mediated neutralization of human immunodeficiency virus type 1 (HIV-1). Antisera were raised in monkeys (Macaca fascicularis) against a series of 40 overlapping synthetic peptides covering the entire amino acid sequence of gp120 from the HTLV-IIIB strain of HIV-1. Immune sera against 12 of these peptides were reactive with gp120 by immunoblotting analysis, and antisera raised against 5 peptides, corresponding to amino acids (aa) 152-176, 193-218, 206-230, 248-269, and 307-330, were highly efficient in neutralizing HIV-1 (HTLV-IIIB) infectivity in vitro. Admixture of individual neutralizing anti-peptide monkey sera resulted in increment in neutralizing antibody titer. Antisera with reactivity to the relatively conserved regions defined by aa 152-176, 193-230, and 248-269 also neutralized to different extents the infectivity of the five Swedish clinical isolates of HIV-1 tested. Only a few HIV-1-infected people were found to make antibodies to these three conserved domains of gp120 as judged by ELISA using synthetic peptides as antigens. Three of the peptides (aa 152-176, 248-269, and 307-330) that induced neutralization antibodies also induced interleukin 2 production and lymphocyte proliferation when added to cultures of peripheral blood mononuclear cells from monkeys immunized with the corresponding peptides, indicating that these domains accommodate T-cell recognition sites. The results have obvious implications for the rational design of subunit vaccines against HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

Effects of manganese oxide on monkeys as revealed by a combined neurochemical, histological and neurophysiological evaluation.

Four monkeys were exposed to a total of 8 g each of manganese as oxide by repetitive subcutaneous injections during 5 months, after which they were left for 1 week to 6 months before they were sacrificed. All animals developed hyperactive behaviour after about 2 months. About 5 months after the start of the exposure the animals became hypoactive with an unsteady gait, and subsequently an action tremor appeared in some of the animals. The animals lost power in both upper and lower limbs and the movements of the hands and feet were very clumsy. The serum content of manganese rose 10-40 times during the exposure time and the content in brain was generally increased more than 10 times, with the highest content found in globus pallidus and putamen. The observed neurochemical effects were also largest in globus pallidus and putamen. In these regions there was a considerable depletion of dopamine and 3,4-dihydroxyphenylacetic acid, while the homovanillic acid content remained almost unchanged. A severe neuronal cell loss was observed in globus pallidus but not in other regions. This is in accordance with results from the most recent neuropathological study of a human suffering from chronic manganese poisoning [Yamada et al. (1986) Acta Neuropathol 70: 273-278] where globus pallidus was devoid of neuronal cells while the content of pigmented cells in substantia nigra was normal. Our data suggest a reduction in number of dopaminergic nerve terminals, as the activity of the dopamine synthesizing enzyme DOPA-decarboxylase was also lowered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Experimental meningitis in the rabbit. I. Arterial blood pressure and acid-base balance during halothane anesthesia and in situ freezing of the brain.

Effects of halothane/N2O anesthesia and in situ freezing of the brain on mean arterial blood pressure (MABP), pH, pCO2 and pO2 were evaluated in rabbits with either Streptococcus pneumoniae or Escherichia coli meningitis. Prior to anesthesia infected rabbits had, compared to controls, significantly lower values for MABP and pCO2, either with a compensated (S. pneumoniae group) or decompensated (E. coli group) metabolic acidosis. In most animals a slight additional decrease in MABP was observed during anesthesia. With maintained pre-anesthetic hypocapnia no further disturbance in acid-base balance occurred during anesthesia. After one minute of freezing MABP increased towards preanesthetic levels. We conclude that the technique for in situ freezing of the brain under halothane/N2O anesthesia may be applied for studies of cerebral metabolism in rabbit with experimental meningitis.

Acid-Base Equilibrium↗

Experimental bacterial meningitis in the rabbit: cerebrospinal fluid changes and its relation to leukocyte response.

This study was focused on cerebrospinal fluid (CSF) manifestations in experimental Streptococcus pneumoniae and Escherichia coli meningitis in rabbits. An increased (p less than 0.001) CSF lactate concentration was found in infected animals, mostly not accompanied by a decrease in CSF glucose concentrations. Despite a marked difference in CSF cellular response between the 2 etiological groups no significant difference in CSF lactate levels was found. Neither did CSF lactate levels correlate to CSF polymorphonuclear cell counts. CSF concentrations of albumin were with large variations above control levels in all infected animals. Also a small or moderate increase in CSF albumin levels was generally associated with a marked increase in CSF lactate concentration. The concentration of total amino acids in the CSF was above control values (mean + 2 SD) in 9/21 infected animals. Halothane/N2O anesthesia for 25 min increased (p less than 0.05) CSF levels of glucose, partly independent of alterations in plasma glucose concentrations, in both infected rabbits and in controls.

Amino Acids↗

Endosseus titanium implants in extraction sockets. An experimental study in monkeys.

In a series of monkeys, titanium implants (Xenodent) were installed in the sockets of mandibular incisors. The animals were sacrificed 7 and 12 weeks after the implantations. The healing was studied by histological and microradiographical techniques. A gradual osseointegration free from adverse interference could be noticed.

Alveolar Process↗

Periodontal ligament injection. An experimental study in the monkey.

In an experimental double blind, cross-over study in monkeys, the reactions of the periodontal tissue after periodontal ligament injection of local anaesthetic solution were investigated. Lidocaine 20 mg/ml with adrenaline 12.5 micrograms/ml and mepivacaine 30 mg/ml were used, and the injection times were 5 or 20 s. Histopathological analysis showed cell damage in the tissues near the injection areas immediately after the experimental procedure. In the specimens obtained one week after the periodontal ligament injections, the tissues were found to be normal.

Alveolar Process↗

Protective effect of polystyrene liners for composite resin restorations.

The main purpose of lining cavities before insertion of composite resin restorations is to prevent bacterial contamination at the cavity walls. A thin film of polystyrene liner dissolved in ethyl acetate applied to all surfaces by compressed air provided good protection against bacteria on cavity walls under composite resin restorations. An antibacterial primer in an alcohol solution applied prior to the liner may improve this protection. This procedure had no detectable injurious effect on the pulp.

Animals↗

Storage of experimentally avulsed teeth in milk prior to replantation.

Extracted monkey teeth were endodontically treated, stored in milk or saliva for two or six h, and then replanted. Periodontal conditions were evaluated after eight wk. Teeth that had been stored for two or six h in milk or for two h in saliva showed periodontal healing almost as good as that of immediately replanted teeth. Teeth that had been kept in saliva for six h or bench-dried for one h showed extensive replacement resorption. Milk may thus be recommended as a storage medium for ex-articulated teeth prior to replantation in cases when immediate replantation is not possible.

Animals↗

Periodontal healing of replanted monkey teeth prevented from drying.

Root resorption of replanted teeth is dependent on the duration of the extra-alveolar period and on the storage environment. In the present investigation the significance of preserving the humidity of the periodontal ligament (PDL) during the extra-alveolar period was tested on isolated PDL cells and on replanted monkey teeth. The isolated PDL cells were tested with respect to cell viability (trypan blue exclusion test) and to cell recovery (number of cells after additional cultivation). About 70% of the cells were viable and 44% recovered after 1 h in a humid atmosphere. Practically no cells were viable or recovered after 1 h of drying. Replanted teeth that had been wrapped in plastic foil for 1 h before replantation showed no more resorption than immediately replanted teeth. This is in contrast to teeth dried in air for 1 h before replantation. They showed extensive root resorption on almost all root surfaces. Thus, prevention of evaporation of tissue fluid from the PDL must be considered a primary goal if the tooth cannot be replanted immediately.

Animals↗

Glucan-induced enhancement of host resistance in experimental intraabdominal sepsis.

Glucan, a 1-3-polyglucosidic component of the cell wall of Saccharomyces cerevisiae, was evaluated for its ability to alter survival in rats with induced intraabdominal sepsis. In four groups, each of 15 rats, the bacteriological flora was changed into that of humans by giving the animals a meat chew. Intraabdominal sepsis was induced by resecting 1 cm of the intestine and reimplanting it in the abdominal cavity after reestablishing the intestinal continuity by one-layer end-to-end anastomosis. The rats were injected with either glucan or isovolumetric saline or benzylpenicillin or glucan plus benzylpenicillin. The results indicate no significant difference in mortality rate between the groups treated with either glucan or benzylpenicillin on the one hand and, on the other, the group given saline alone. However, the group treated with glucan plus benzylpenicillin differed significantly from the control group given just saline. The bacterial flora did not seem to be influenced by glucan administration. It is concluded that glucan has a clear effect on the survival rate of rats with induced peritonitis, probably by enhancing the activities of the reticuloendothelial system--an important part of the total host resistance.

Abdomen↗

The effect of glucan--a host resistance activator--and ampicillin on experimental intraabdominal sepsis.

Glucan, a beta-1-3-polyglucosidic component of the cell wall of Saccharomyces cervisiae, was evaluated for its ability to influence the survival rate in rats with induced intraabdominal sepsis. To mimic closely the human bacteriological intestinal flora, the rats, in 4 groups each of 15 animals, were fed a lean meat diet. Intraabdominal sepsis was induced by resecting 1 cm of the intestine and reimplanting it in the abdominal cavity, reestablishing intestinal continuity by one-layer end-to-end anastomosis. The rats were injected with glucan, isovolumetric saline, and ampicillin or glucan plus ampicillin. The results indicate a significant decrease in mortality in the group treated with ampicillin compared with the group treated with saline only. The group treated with glucan plus ampicillin differed significantly from the group given ampicillin. The bacterial flora was not qualitatively influenced by glucan administration. It is concluded that glucan, in combination with ampicillin, has a significant effect on the survival rate of rats with induced peritonitis, probably by enhancing the activities of the reticuloendothelial system--an important part of the total host resistance.

Abscess↗

Vitality of periodontal ligament cells after storage of monkey teeth in milk or saliva.

Vitality of the periodontal ligament (PDL) is necessary for a successful healing after replantation of exarticulated teeth. In the present investigation newly extracted teeth from monkeys were stored in saline, milk or saliva for 1-3 h. Freeze sections were made and the vitality of the PDL was determined histochemically. Milk seemed to provide better storage conditions than saliva or saline.

Animals↗

Pyrazoles as inhibitors of alcohol oxidation and as important tools in alcohol research: an approach to therapy against methanol poisoning.

4-Methylpyrazole, in a dose producing inhibition of alcohol dehydrogenase (alcohol:NAD(+) oxidoreductase, EC 1.1.1.1), was given alone or together with ethanol (10%) as sole drinking fluid to growing rats for up to 38 weeks. Their weight curves remained normal. Electron microscopy of liver, kidney, and heart revealed no changes related to treatment. Hematologic analysis showed normal values for blood and bone marrow. Several clinical chemical parameters showed no impairment of liver or kidney function, except for an enhancement of the microsomal drug-metabolizing activity after concurrent administration of 4-methylpyrazole and ethanol. A study on rats receiving 4-methylpyrazole and ethanol indicated a mutual interaction of the two compounds or the metabolites, leading to increased concentration in the blood of the compounds and reduced formation of 4-hydroxymethylpyrazole, the primary metabolite of 4-methylpyrazole. In monkeys, elimination of 4-methylpyrazole followed a linear course. 4-Hydroxymethylpyrazole accumulated to a level of at most 10% of that of 4-methylpyrazole. Concurrent administration of methanol inhibited the elimination of 4-methylpyrazole about 25%, and 4-methylpyrazole produced a profound inhibition of the oxidation of methanol. 4-Methylpyrazole, at a level in the plasma of more than 10 muM, prevented accumulation of the toxic metabolite formic acid in methanol-poisoned monkeys, and repeated injections of 4-methylpyrazole abolished methanol toxicity in monkeys receiving lethal doses of methanol. The present investigation indicates that 4-methylpyrazole, with its low toxicity and strong inhibition of alcohol oxidation, is a valuable tool for experimental studies of alcohol metabolism and its effects. It illustrates the usefulness of the monkey as a model to study 4-methylpyrazole activity and toxicity in light of its possible use for treating methanol poisoning in human beings.

Alcoholism↗