| 1. |
- Abdul-Rahman, A, et al.
(författare)
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Local cerebral blood flow in the rat during severe hypoglycemia, and in the recovery period following glucose injection
- 1980
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 109:3, s. 307-314
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Tidskriftsartikel (refereegranskat)abstract
- In order to assess the influence of severe hypoglycemia on local cerebral blood flow (1-CBF) artificially ventilated rats, maintained on 70% N2O, were injected with insulin to provide either an EEG pattern of slow-wave polyspikes, or cessation of spontaneous EEG activity for 5, 15 or 30 min ("coma"). In other animals, glucose was injected at the end of a 30 min period of "coma" and 1-CBF was measured after recovery periods of 5, 30, 90, or 180 min. Local CBF was measured autoradiographically with 14C-iodoantipyrine as the diffusible tracer. In the slow-wave polyspike period 1-CBF was increased in most of the structures studied, and reached values that were 1.4 to 3.2 times greater than control. In many structures, cessation of EEG activity was accompanied by a further increase in 1-CBF, with some structures (thalamus, hypothalamus, pontine gray, and cerebellar cortex) showing flow rates of 400--500% of control. The increase in 1-CBF was unrelated to arterial hypertension, hypercapnia, or hypoxia. 5 min after glucose injection the hyperemia persisted in only some of the structures studied; in others, the 1-CBF were close to, or below, control values. During the subsequent recovery period 1-CBF was markedly reduced with some structures (cerebral cortical areas, hippocampus, and caudate-putamen) showing flow rates of only 20--35% of control. In others, notably pontine gray and cerebellar cortex, secondary hypoperfusion was never observed. The hypoperfusion was unrelated to arterial hypertension, hypocapnia, or increase in intracranial pressure. It is concluded that, like hypoxia and ischemia, substrate deficiency due to hypoglycemia is accompanied by vasodilatation in the brain. Furthermore, like long-lasting ischemia, severe hypoglycemia is followed by a delayed hypoperfusion syndrome that, by restricting oxygen supply, may well contribute to the final cell damage incurred.
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| 2. |
- Agardh, Carl-David, et al.
(författare)
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Desensitisation as a means of preventing untoward reactions to ionic contrast media
- 1983
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Ingår i: Acta Radiologica Diagnosis. - 0567-8056. ; 24:3, s. 235-239
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Tidskriftsartikel (refereegranskat)abstract
- Patients with a previous history of anaphylactic reactions to ionic iodinated contrast media were desensitised before a second radiologic examination was performed. The tolerance to the contrast medium was raised by repeated intravenous injections in increasing doses and concentrations. No serious side effects were noted when the examinations with contrast medium was repeated within a few days after the desensitisation. The positive effect of the desensitisation may depend on a successive consumption of complement proteins, probably responsible for the allergic reactions. Therefore, the available amount of complement for some days may be too low for the occurrence of a complement reaction.
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| 3. |
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| 4. |
- Agardh, Carl-David, et al.
(författare)
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Endogenous substrates utilized by rat brain in severe insulin-induced hypoglycemia
- 1981
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Ingår i: Journal of Neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 36:2, s. 490-500
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Tidskriftsartikel (refereegranskat)abstract
- Several previous studies have demonstrated that severe hypoglycemia is accompanied by consumption of endogenous brain substrates (glycolytic and citric acid cycle metabolites and free amino acids) and some have shown a loss of structural components as well, notably phospholipids. In the present study, on paralysed and artificially ventilated rats, we measured cerebral oxygen and glucose consumption during 30 min of hypoglycemic coma (defined as hypoglycemia of sufficient severity to cause cessation of spontaneous EEG activity) and calculated the non-glucose oxygen consumption. In an attempt to estimate the missing substrate we measured tissue concentrations of phospholipids and RNA. After 5 min of hypoglycemic coma, tissue phospholipid content decreased by about 8% with no further change during the subsequent 55 min. A similar reduction remained after 90 min of recovery, induced by glucose administration following 30 min of coma. Since no preferential loss of polyenoic fatty acids or of ethanolamine phosphoglycerides occurred, it is concluded that loss of phospholipids was due to phospholipase activity rather than to peroxidative degradation. The free fatty acid concentration increased sixfold after 5 min of coma and remained elevated during the course of hypoglycemia. A 9% reduction in tissue RNA content was observed after 30 min of hypoglycemia. Calculations indicated that available endogenous carbohydrate and amino acid substrates were essentially consumed after 5 min of coma, and that other non-glucose substrates must have accounted for approximately 50μmol·g−1 of oxygen (8.3 μmol·g−1 in terms of glucose equivalents) within the 5–30 min period. The 10% reduction in phospholipid-bound fatty acids was more than sufficient (in four- to fivefold excess) to account for this oxygen consumption. However, since no further degradation occurred in the 5–30 min period, there is no simple, direct, quantitative relationship between oxygen consumption and cortical fatty acid oxidation during this interval. The possibility thus remains that unmeasured exogenous or endogenous substrates were utilized.
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| 5. |
- Agardh, Carl-David, et al.
(författare)
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Hypoglycemic brain injury. I. Metabolic and light microscopic findings in rat cerebral cortex during profound insulin-induced hypoglycemia and in the recovery period following glucose administration
- 1980
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Ingår i: Acta Neuropathologica. - 1432-0533. ; 50:1, s. 31-41
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Tidskriftsartikel (refereegranskat)abstract
- Profound hypoglycemia causing the disappearance of spontaneous EEG activity was induced by insulin in rats. For analysis of cerebral cortical concentrations of labile phosphates, glycolytic metabolites and amino acids, the brain was frozen in situ. For microscopic analysis of the corresponding cerebral cortical areas the brain was fixed by perfusion. Hypoglycemia with an isoelectric EEG for 30 and 60 min caused severe perturbation of the cerebral energy metabolites. After both 30 and 60 min of isoelectric EEG, two microscopically different types of nerve cell injury were seen. Type I injury was characterized by angulated, darkly stained neurons with perineuronal vacuolation, mainly affecting small neurons in cortical layer 3. Type II injured neurons, mainly larger ones in layers 5–6, were slightly swollen with vacuolation or clearing (depending on the histotechnique used) of the peripheral cytoplasm, but had no nuclear changes. Recovery was induced by glucose injection. Improvement in the cerebral energy state occurred during the 30 min recovery period even after 60 min of hypoglycemia. However, the persisting reduction in the size of adenine nucleotide and amino acid pools after 30 or 180 min recovery suggested that some cells remained damaged. In confirmation many type I injured neurons persisted during the recovery suggesting an irreversible injury. The disappearance of virtually all type II injuries indicated reversibility of these histopathological changes. The microscopic changes in hypoglycemia were different from those in anoxia-ischemia suggesting a dissimilar pathogenesis in these states despite the common final pathway of energy failure.
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| 6. |
- Agardh, Carl-David, et al.
(författare)
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Hypoglycemic brain injury: metabolic and structural findings in rat cerebellar cortex during profound insulin-induced hypoglycemia and in the recovery period following glucose administration
- 1981
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - 1559-7016. ; 1:1, s. 71-84
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Tidskriftsartikel (refereegranskat)abstract
- Previous results have shown that severe, prolonged hypoglycemia leads to neuronal cell damage in, among other structures, the cerebral cortex and the hippocampus but not the cerebellum. In order to study whether or not this sparing of cerebellar cells is due to preservation of cerebellar energy stores, hypoglycemia of sufficient severity to abolish spontaneous EEG activity was induced for 30 and 60 min. At the end of these periods of hypoglycemia, as well as after a 30 min recovery period, cerebellar tissue was sampled for biochemical analyses or for histopathological analyses or for histopathological analyses by means of light and electron microscopy. After 30 min of hypoglycemia. the cerebellar energy state, defined in terms of the phosphocreatine, ATP, ADP, and AMP concentrations, was better preserved than in the cerebral cortex. After 60 min, gross deterioration of cerebellar energy state was observed in the majority of animals, and analyses of carbohydrate metabolites and amino acids demonstrated extensive consumption of endogenous substrates. In spite of this metabolic disturbance, histopathologic alterations were surprisingly discrete. After 30 min, no clear structural changes were observed. After 60 min, only small neurons in the molecular layer (basket cells) were affected, while Purkinje cells and granule cells showed few signs of damage. The results support our previous conclusion that the pathogenesis of cell damage in hypoglycemia is different from that in hypoxia-ischemia and indicate that other mechanisms than energy failure must contribute to neuronal cell damage in the brain.
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| 7. |
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| 8. |
- Agardh, Carl-David, et al.
(författare)
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Improvement of peripheral nerve function after institution of insulin treatment in diabetes mellitus. A case-control study
- 1983
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Ingår i: Acta Medica Scandinavica. - 0001-6101. ; 213:4, s. 283-287
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Tidskriftsartikel (refereegranskat)abstract
- The influence of improved diabetic control on peripheral nerve function was studied before and 3-4 months after institution of insulin treatment in 22 diabetics unsatisfactorily controlled by oral hypoglycemic agents. After institution of insulin treatment, diabetic control was improved as demonstrated by decreasing levels of HbA1. There was an overall tendency towards improvement of motor and sensory conduction velocities, however significant only in the upper extremities. There was a tendency towards improved temperature sensitivity in the legs, while no changes occurred in the hands and face. The sensation for vibration did not change. It is concluded that improved diabetic control, even in elderly patients with long-standing diabetes, is followed by neurophysiological signs of improved peripheral nerve function.
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| 9. |
- Agardh, Carl-David, et al.
(författare)
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Improvement of the plasma lipoprotein pattern after institution of insulin treatment in diabetes mellitus
- 1982
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 5:3, s. 322-325
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Tidskriftsartikel (refereegranskat)abstract
- Plasma lipids and lipoproteins were studied in 26 nonobese diabetic patients, either newly diagnosed or unsatisfactorily controlled by oral antidiabetic treatment. Measurements were performed before and 3-4 mo after the institution of insulin treatment. In a subgroup of seven patients, the activities of lipoprotein lipase (LPL) and hepatic lipase (HL) in postheparin plasma and the elimination rate of exogenous triglyceride were also monitored. After beginning insulin treatment, diabetic control was improved as demonstrated by decreasing levels of HbA1. Mean plasma cholesterol and triglyceride levels decreased by about 10% (P less than 0.01) and 40% (P less than 0.05), respectively. The decrease in plasma cholesterol was largely accounted for by a fall in LDL cholesterol levels (-8%, P less than 0.05), while plasma HDL cholesterol concentrations increased by about 12% (P less than 0.01). The elimination rate of exogenous triglycerides increased significantly. There was a suggestive, but not significant, increase in LPL activity while the HL activity remained unchanged. It is concluded that the improved diabetic control after institution of insulin treatment results in a significant improvement of the plasma lipoprotein profile. Since the improvement of the lipoprotein pattern is not strictly correlated to the amelioration of indices reflecting glucose transport, we suggest that the plasma lipoprotein pattern may provide an additional tool for monitoring the degree of control in diabetes mellitus.
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| 10. |
- Agardh, Carl-David, et al.
(författare)
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Influence of severe hypoglycemia on mitochondrial and plasma membrane function in rat brain
- 1982
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Ingår i: Journal of Neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 38:3, s. 662-668
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: Previous experiments have shown that severe hypoglycemia disrupts cerebral energy state in spite of a maintained cerebral oxygen consumption, suggesting uncoupling of oxidative phosphorylation. Other studies have demonstrated that hypoglycemia leads to loss of cerebral cortical phospholipids and phospholipid-bound fatty acids. The objective of the present study was, therefore, to study respiratory characteristics of brain mitochondria during severe hypoglycemia and to correlate respiratory activity to mitochondrial phospholipid composition. Mitochondria were isolated after 30 or 60 min of hypoglycemia with ceased EEG activity, and after a 90-min recovery period, and their resting (state 4) and ADP-stimulated (state 3) oxygen consumption rates and phospholipids and phospholipid-bound fatty acid content were measured. After 30 min of hypoglycemia, state 3 respiration decreased without any increase in state 4 respiration or change in ADP/O ratio. This decrease, which occurred with glutamate plus malate—but not with succinate—as substrates, was partly reversed by addition of bovine serum albumin and KCI. Chemical analyses of isolated mitochondria did not reveal changes in their phospholipid or fatty acid content. The results thus failed to account for the dissociation of cerebral energy state and oxygen consumption. It is emphasized, though, that uncoupling may well occur in vivo due to accumulation of free fatty acids and "futile cycling" of K+ and Ca2+. After 60 min of hypoglycemia, a moderate decrease in state 3 respiration was observed also with succinate as substrate, and there was some decrease in ADP/O ratios in KCI-containing media. However, the changes in ADP/O ratios were more conspicuous during recovery; in addition, state 4 respiration increased significantly. It is concluded that changes in mitochondrial function after 30 min of hypoglycemia are potentially reversible but that true mitochondrial failure develops in the recovery period following 60 min of hypoglycemia. This conclusion was corroborated by results demonstrating incomplete recovery of cerebral energy state. Since EEG and sensory evoked potentials return after 30 min but not after 60 min of hypoglycemia it seemed difficult to explain failure of return of electrophysiological function after 60 min of hypoglycemia solely by mitochondrial dysfunction; plasma membrane function was therefore assessed by measurements of extracellular potassium activity ([K+]e). The results showed that whereas [K+]e remained close to control in the recovery period following 30 min of hypoglycemia it rose progressively during recovery following 60 min of hypoglycemia. Possibly, inhibition of Na+ K+–activated ATPase could contribute to the permanent loss of spontaneous or evoked electrical activity.
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