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Biomedical subjects

B Nilsson

Publications and source records attributed to B Nilsson.

At least 631 records · Page 35Linked to original sources

The influence of hypoxia on the concentrations of cyclic nucleotides in the rat brain.

In order to study the influence of hypoxia on cyclic nucleotides in the brain, we reduced arterial Po(2) for 15-30 min in lightly anaesthetised and artificially ventilated rats to obtain values ranging from about 45 to about 10 mm Hg. In an additional group (arterial Po(2) 18-22 mm Hg), the tissue hypoxia was aggravated by moderate arterial hypotension (mean arterial blood pressure about 80 mm Hg). In all animals, electrocortical activity was recorded. Cyclic GMP concentrations in cerebral cortex were unchanged in all groups but one. In that group, in which tissue hypoxia was severe enough to induce a suppression-burst EEG pattern and a measurable reduction in the adenylate energy charge, cyclic GMP concentrations were slightly increased (p less than 0.05). Cyclic AMP concentrations remained unaltered at all degrees of hypoxia studied. It is concluded that changes in cyclic nucleotides in brain tissue occur first at such severe degrees of hypoxia of the duration studied that function and metabolism are profoundly altered.

Animals↗

Free fatty acids in the rat brain in moderate and severe hypoxia.

The effects of mild, moderate, and severe hypoxia on cerebral cortical concentrations of free fatty acids (FFAs) were investigated in artificially ventilated rats under nitrous oxide anaesthesia. No change occurred during either mild (arterial PO2 35-40 mm Hg) or moderate (PO2 25-30 mm Hg) hypoxia. The effects of severe hypoxia (PO2 about 20 mm Hg) combined with hypotension (mean arterial blood pressure 80-85 mm Hg) varied with the EEG pattern and the tissue energy state. Thus, a major increase in total as well as in individual FFAs occurred first when EEG was severely depressed (almost isoelectric) and energy homeostasis disrupted. On a relative basis the greatest change occurred in free arachidonic acid. It is concluded tha hypoxia is associated with an increase in the concentrations of FFAs in brain tissue, provided that tissue oxygen deficiency is severe enough to cause tissue energy failure. However, an increase in FFAs does not invariably accompany minor reductions in the adenylate energy charge (EC) of the tissue.

Adenine Nucleotides↗

Opening of the blood-brain barrier by acute elevation of intracarotid pressure.

A method for local opening of the blood-brain barrier in the territory of one internal carotid artery in the rat is described. A local hypertensive insult is induced by rapid infusion of blood into the internal carotid via the external carotid. The hemodynamic changes caused by the infusion, in particular relation to the threshold and extent of barrier opening, are analyzed. This mode of hypertensive barrier opening may be advantageous to those in which the insult is induced systematically, especially when studying the cerebrovascular effects of neurotransmitter catecholamines, since all the latter methods interfere with adrenergic mechanisms. Further, unilateral intracarotid infusion may allow the territory of the contralateral middle cerebral artery to be used as internal control.

Animals↗

Local cerebral blood flow in the brain during bicuculline-induced seizures and the modulating influence of inhibition of prostaglandin synthesis.

The purpose of this study was to measure changes in local cerebral blood flow (1-CBF) during generalized seizures, and to study whether or not formation of prostaglandins or related substances contributes to the increased flow rates. Seizures were induced in ventilated rats maintained on 70% N2O and 30% O2 by the i.v. injection of the GABA receptor blocker bicuculline (1.2 mg . kg-1). Formation of prostaglandins was inhibited by the administration of the fatty acid cyclo-oxygenase inhibitor indomethacin (10 mg . kg-1). Local CBF in 21 defined brain structures was measured autoradiographically with 14C-iodoantipyrine as the diffusible tracer. After 20 min of continuous seizure activity 1-CBF increased 1.5--5-fold, the smallest increases (less than 200% of control) being observed in frontal and auditory cortex and in the caudoputamen, and the largest (greater than 400% of control) in substantia nigra, thalamus, visual cortex, lateral geniculate and hypothalamus. In general, the largest increases in 1-CBF occurred in sensory and limbic systems (and hypothalamus) while motor systems showed a pronounced variability. In the majority of structures examined indomethacin failed to modify the CBF response during seizures. Although this result suggests that seizures, in contrast to hypercapnia, lead to an increased CBF by other mechanisms than those related to prostaglandin formation, some structures (nucleus ruber, cerebellum, and superior colliculus) showed a clearly reduced 1-CBF in indomethacin-treated animals.

Animals↗

Cerebrovascular response during and following severe insulin-induced hypoglycemia: CO2-sensitivity, autoregulation, and influence of prostaglandin synthesis inhibition.

The objective of the present experiments was to study mechanisms governing cerebrovascular responses during severe hypoglycemia, and in the posthypoglycemic recovery period. To that end, lightly anesthetized (70% N2O) and artificially ventilated rats were injected with insulin so as to abolish spontaneous EEG activity for 15 or 30 min ("coma"). In separate animals, recovery was induced by glucose administration. Previous experiments have shown that in normo- or moderately hypertensive animals hypoglycemic coma is accompanied by a relatively marked increase in cerebral blood flow (CBF), and that a delayed hypoperfusion develops in the recovery period. The present results demonstrate that oxygen supply is in excess of the demands during coma, and falls below control during recovery. During hypoglycemic coma, the CO2 response of the circulation was retained but autoregulation was lost. In the recovery period, both CO2 response and autoregulation were lost. Pretreatment with indomethacin was introduced in order to evaluate the possible influence of fatty acid cyclo-oxygenase products on the pattern of CBF changes. Measurements of local cerebral blood flow (1-CBF) showed that, in the majority of structures analysed, indomethacin failed to modulate the changes in CBF. It is concluded that alterations in cerebrovascular tone and loss of autoregulation induce flow changes that may influence substrate and oxygen availability during hypoglycemia. The pronounced decrease in CBF and the loss of autoregulation and CO2-response in the post-hypoglycemic period may influence functional, metabolic and morphological recovery. The 1-CBF findings indicate that neither the increase in CBF during hypoglycemia nor the reduction in flow in the posthypoglycemic period are mediated by mechanisms related to prostaglandin metabolism.

Animals↗

The effect of indomethacin on cerebral blood flow and oxygen consumption in the rat at normal and increased carbon dioxide tensions.

The effect of the fatty acid cyclo-oxygenase inhibitor indomethacin on cerebral blood flow (CBF) and the metabolic rate for oxygen (CMRO2) was studied in paralyzed and artificially ventilated rats. In normocapnic animals, the drug (10 mg.kg-1i.v.) reduced CBF to 50% of control without a measurable effect on CMRO2. During hypercapnia (PaCO2 70-80 mmHg) the increase in CBF was reduced by about 80% but CMRO2 remained unchanged. Autoradiographic evaluation of local CBF in 20 brain structures indicated that the reduction in CBF was relatively uniform throughout the brain. Dose response curves showed that an effect on CBF was evident already at an indomethacin dose of 1 mg.kg-1 and maximal effects were obtained with 3-5 mg.kg-1. Following i.v. injection of the drug reduction in CBF was observed already after 10 s and the full response occurred after 1-2 min. It is concluded that metabolites of arachidonic acid, possibly mainly prostacyclin, are powerful modulators of normal cerebrovascular tone, and help to mediate the CBF response to increased CO2 tensions. However, since indomethacin does not modify the circulatory response in other conditions with increased CBF these substances do not qualify as general coupling factors controlling CBF in physiological or pathological states.

Animals↗

Sleep apnea syndrome--an alternative treatment to tracheostomy.

Two patients with obstructive sleep apnea syndrome had polygraphic recordings demonstrated upper airway obstruction and sleep with extremely short sleep latency, severely disturbed nightsleep resulting in sleep deprivation, and excessive daytime sleepiness. Radiological investigation showed the upper airway obstruction to be caused by the tongue falling back occluding the pharynx. Nasopharyngeal intubation relieved the symptoms. The patients were trained to perform this treatment themselves every night, demonstrating that this treatment is an attractive alternative to the conventional tracheotomy.

Disorders of Excessive Somnolence↗

Contamination of high-energy photon beams by scattered photons.

Absorbed dose and energy distribution of scattered photons that contaminate high-energy photon beams have been calculated for 6-MV and 21-MV bremsstrahlung sources using the Monte Carlo method. The percentage of the absorbed dose at the central axis is less than 3%. The results show that the main sources of scattered photons are the primary collimator for 6-MV and the flattening filter for 21-MV bremsstrahlung sources respectively. The absorbed dose from the phantom scattered photons has been calculated by a semi-empirical method. These calculations show that the dominating contribution to the absorbed dose outside the primary beam is due to these phantom scattered photons. In the surface region of the phantom, however, electrons from the air and collimators may give rise to a high absorbed dose.

Electrons↗

Oligosaccharides on proteoglycans from the swarm rat chondrosarcoma.

Two classes of oligosaccharides were identified in alkaline borohydride digests of monomer proteoglycans from the Swarm rat chondrosarcoma. The first class consists of three similar oligomers, each of which is linked to the proteoglycan core proteins by an O-glycosidic bond between N-acetylgalactosamine and hydroxyl groups on serine and threonine. The structures of the two smallest oligosaccharides are: (formula: see text). Proteoglycan monomers from the chondrosarcoma contain about 1.3 of these oligosaccharides for every chondroitin sulfate chain. Their structures and distribution on the core protein suggest that they are related to the linkage region between keratan sulfate chains and the core protein of cartilage proteoglycans. The second class of oligomers consists of oligosaccharide-peptides that contain mannose and are probably linked to the core protein by N-glycosylamine bonds to asparagine. There appear to be about 15 of these oligosaccharides/ proteoglycan molecule, and they are primarily located on the core protein nearer to the hyaluronic acid-binding site than both the oligosaccharides linked by O-glycoside bonds and the chondroitin sulfate chains. Chondrocytes isolated from the chondrosarcoma and grown in culture synthesize both classes of oligosaccharides.

Acetylgalactosamine↗

Hemodynamic changes in brain caused by local infusion of hyperosomolar solutions, in particular relation to blood-brain barrier opening.

The intracarotid infusion of hyperosmolar aqueous solutions such as urea is widely used to transiently open the blood-brain barrier in various animal species. In the present study in the rat an attempt was made to analyze the hemodynamic changes caused by the intracarotid infusions with special reference to possible mechanisms underlying the barrier opening. The cerebral blood flow (as reflected by the cerebral venous outflow rate) intracranial pressure, intracarotid pressure and systemic blood pressure were continuously measured during and following the infusions. It was found that intracarotid infusions of hyperosomolar solutions induce cerebral vasodilation and flow increase. Autoregulation is impaired. Probably, a direct vasodilator mechanism is involved but, depending on volume and osmolarity of the solution used, the changes may be heavily influenced by vascular distention due to intracarotid pressure effect, and by systemic pressure changes. These mechanisms are in common with other methods for barrier opening. The local vasomotor and systemic effects of a hyperosmolar solution of urea, capable of opening the barrier, are not normalized until about 6 min after the administration.

Animals↗

Neurology and behaviour of growth-retarded neonates. Relation to biochemical placental function tests in late pregnancy.

Serial estimations of maternal urinary oestriol, serum cystine aminopeptidase (S-CAP), and human chorionic somatomammotrophin (S-HCS) were done in a prospective study on 29 pregnancies in which intrauterine growth retardation was diagnosed in the third trimester by the gravidogram method and/or serial ultrasound measurements of the fetal biparietal diameter. The series was divided into 2 growth-retarded groups: (i) severe growth retardation with birth weight less than -2 SD from the mean for gestational age (N = 14); (ii) moderate growth retardation with birth weight between -1 and -2 SD from the mean for gestational age (N = 15). These were compared with a control group of 18 normal pregnancies and infants. A modified Prechtl neurological examination and the Brazelton Neonatal Behavioural Assessment Scale (NBAS) were done in the neonatal period at full-term age. Both categories of growth-retarded infants showed lower muscle tonus than the controls. The severely growth-retarded infants showed fewer optimal items in the neurological examination; they also showed poorer capacity for orientation to external stimuli, inferior motor function, and less physiological stability in NBAS than the controls. The abnormal biochemical placental tests were significantly correlated to low Apgar scores (urinary oestriol), to low excitability (S-CAP) and to poor motor function (S-HCS). The neurological and behavioural condition of the neonate seemed to be more closely associated to the extent of growth retardation than to the occurrence of abnormal biochemical placental tests.

Adult↗

The effect of metastasectomy: fact or fiction?

Metastasectomy in the treatment of solitary metastases has been recommended almost unanimously. The basis for this recommendation has been that 5-year survival after metastasectomy is around 30%, which is just as good as after operation for bronchial carcinoma. It has been assumed, implied, or claimed that the 5-year survival without operation is nil. Control material is, however, lacking. Seventy surgically treated patients were compared with a small, historical control group of 12 patients. There was no difference in 5-year survival. Because of these findings and after a study of the literature, we postulate that patients with lung metastases fulfilling the criteria for operation constitute a selected group with a favorable natural history. Five-year survival, therefore, is an insufficient way of describing the effect of metastasectomy. However, patients with 10-year survival are rare in the literature. In some patients with a favorable tumor-host relationship or with possibilities for effective chemotherapy, cure or prolongation of life has been achieved. Such patients should undergo operation. Randomized studies are needed in all groups for which we do not have sufficiently strong evidence that metastasectomy contributes to the longevity of the patient.

Adult↗

Clinical significance of mitogen-induced responses in lymphocytes from patients with chronic lymphocytic leukemia.

The mitogenic response patterns as well as surface membrane receptors of peripheral blood lymphocytes were investigated repeatedly during progression of the disease in 27 patients with chronic lymphocytic leukemia. Each patient was characterized by a reproducible mitogenic response pattern. Eleven patients, who required treatment within 0-24 months after diagnosis, had significantly higher cellular responses to dextran sulphate (DxS) and lipopolysaccharide (LPS) than 10 patients who have not required treatment within an observation time of 10-40 months from diagnosis. The high LPS and DxS responses, which may indicate leukemias composed of more immature cells, appear to predict a poor prognosis.

Cells, Cultured↗