Göran E. Nilsson

Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study.

BACKGROUND Glycometabolic state at hospital admission is an important risk marker for long-term mortality in patients with acute myocardial infarction, whether or not they have known diabetes mellitus. Our aim was to ascertain the prevalence of impaired glucose metabolism in patients without diagnosed diabetes but with myocardial infarction, and to assess whether such abnormalities can be identified in the early course of a myocardial infarction. METHODS We did a prospective study, in which we enrolled 181 consecutive patients admitted to the coronary care units of two hospitals in Sweden with acute myocardial infarction, no diagnosis of diabetes, and a blood glucose concentration of less than 11.1 mmol/L. We recorded glucose concentrations during the hospital stay, and did standardised oral glucose tolerance tests with 75 g of glucose at discharge and again 3 months later. FINDINGS The mean age of our cohort was 63.5 years (SD 9) and the mean blood glucose concentration at admission was 6.5 mmol/L (1.4). The mean 2-h postload blood glucose concentration was 9.2 mmol/L (2.9) at hospital discharge, and 9.0 mmol/L (3.0) 3 months later. 58 of 164 (35%, 95% CI 28-43) and 58 of 144 (40%, 32-48) individuals had impaired glucose tolerance at discharge and after 3 months, respectively, and 51 of 164 (31%, 24-38) and 36 of 144 (25%, 18-32) had previously undiagnosed diabetes mellitus. Independent predictors of abnormal glucose tolerance at 3 months were concentrations of HbA(1c) at admission (p=0.024) and fasting blood glucose concentrations on day 4 (p=0.044). INTERPRETATION Previously undiagnosed diabetes and impaired glucose tolerance are common in patients with an acute myocardial infarction. These abnormalities can be detected early in the postinfarction period. Our results suggest that fasting and postchallenge hyperglycaemia in the early phase of an acute myocardial infarction could be used as early markers of high-risk individuals.

Evolutionary background for stress-coping styles: relationships between physiological, behavioral, and cognitive traits in non-mammalian vertebrates.

Reactions to stress vary between individuals, and physiological and behavioral responses tend to be associated in distinct suites of correlated traits, often termed stress-coping styles. In mammals, individuals exhibiting divergent stress-coping styles also appear to exhibit intrinsic differences in cognitive processing. A connection between physiology, behavior, and cognition was also recently demonstrated in strains of rainbow trout (Oncorhynchus mykiss) selected for consistently high or low cortisol responses to stress. The low-responsive (LR) strain display longer retention of a conditioned response, and tend to show proactive behaviors such as enhanced aggression, social dominance, and rapid resumption of feed intake after stress. Differences in brain monoamine neurochemistry have also been reported in these lines. In comparative studies, experiments with the lizard Anolis carolinensis reveal connections between monoaminergic activity in limbic structures, proactive behavior in novel environments, and the establishment of social status via agonistic behavior. Together these observations suggest that within-species diversity of physiological, behavioral and cognitive correlates of stress responsiveness is maintained by natural selection throughout the vertebrate sub-phylum.

Near-future carbon dioxide levels alter fish behaviour by interfering with neurotransmitter function

A study of two species of coral reef fish demonstrates that the anticipated increase in atmospheric carbon dioxide directly interferes with neurotransmitter function in their larvae, a hitherto unrecognized problem for marine fishes. Predicted future CO2 levels have been found to alter sensory responses and behaviour of marine fishes. Changes include increased boldness and activity, loss of behavioural lateralization, altered auditory preferences and impaired olfactory function1,2,3,4,5. Impaired olfactory function makes larval fish attracted to odours they normally avoid, including ones from predators and unfavourable habitats1,3. These behavioural alterations have significant effects on mortality that may have far-reaching implications for population replenishment, community structure and ecosystem function2,6. However, the underlying mechanism linking high CO2 to these diverse responses has been unknown. Here we show that abnormal olfactory preferences and loss of behavioural lateralization exhibited by two species of larval coral reef fish exposed to high CO2 can be rapidly and effectively reversed by treatment with an antagonist of the GABA-A receptor. GABA-A is a major neurotransmitter receptor in the vertebrate brain. Thus, our results indicate that high CO2 interferes with neurotransmitter function, a hitherto unrecognized threat to marine populations and ecosystems. Given the ubiquity and conserved function of GABA-A receptors, we predict that rising CO2 levels could cause sensory and behavioural impairment in a wide range of marine species, especially those that tightly control their acid–base balance through regulatory changes in HCO3− and Cl− levels.

Hypoxia induces adaptive and reversible gross morphological changes in crucian carp gills

SUMMARY We show that crucian carp (Carassius carassius) living in normoxic (aerated) water have gills that lack protruding lamellae, the primary site of O2 uptake in fish. Such an unusual trait leads to a very small respiratory surface area. Histological examination showed that the lamellae (secondary lamellae) of these fish were embedded in a cell mass (denoted embedded lamellae). When the fish were kept in hypoxic water, a large reduction in this cell mass occurred, making the lamellae protrude and increasing the respiratory surface area by ∼7.5-fold. This morphological change was found to be reversible and was caused by increased apoptosis combined with reduced cell proliferation. Carp with protruding lamellae had a higher capacity for oxygen uptake at low oxygen levels than fish with embedded lamellae, but water and ion fluxes appeared to be increased, which indicates increased osmoregulatory costs. This is, to our knowledge, the first demonstration of an adaptive and reversible gross morphological change in the respiratory organ of an adult vertebrate in response to changes in the availability of oxygen.

Roles of brain monoamine neurotransmitters in agonistic behaviour and stress reactions, with particular reference to fish

Abstract 1. Experimental results on the involvement of brain monoamines in agonistic behaviour and stress in fish are reviewed and discussed in relation to available data from other vertebrates. 2. In fish as well as mammals, stress induces increased brain serotonergic activity, and a similar increase in serotonergic activity is seen in subordinate individuals in a dominance hierarchy. 3. The brain serotonergic system appears to inhibit aggression and spontaneous locomotor activity in both fish and mammals. 4. Subordinate fish show several behavioural characteristics, notably inhibition of aggressive behaviour, low spontaneous locomotor activity and decreased food intake, that are likely to be related to their increased brain serotonergic activity. 5. By contrast, the brain dopaminergic system appears to stimulate aggressive behaviour in both fish and mammals, and dominant fish show signs of elevated dopaminergic activity in telencephalon. 6. The similarities between fish and mammalian monoaminergic functions suggest that these are phylogenetically very old mechanisms that have been conserved during the last 400 million years of vertebrate evolution.

Serotonin as a regulator of hypothalamic-pituitary-interrenal activity in teleost fish

Evidence for the presence of a serotonin1A (5-HT1A) receptor subtype in the salmonid fish brain has recently been presented. In the present study the potent 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) was tested for its effect on plasma cortisol concentrations in rainbow trout (Oncorhynchus mykiss). Blood was sampled and 8-OH-DPAT administered through a catheter in the dorsal aorta. Thirty minutes after the injection of 40 microg of 8-OH-DPAT/kg, plasma cortisol levels had increased from 12 to 149 ng/ml, whereupon they fell, reaching baseline levels after 4 h. The effect of 1-40 microg 8-OH-DPAT/kg on plasma cortisol concentrations was dose-dependent. The results lends further support to the hypothesis that the brain serotonergic system plays a key role in integrating autonomic, behavioral and neuroendocrine stress-responses in fish as well as mammals, suggesting that not only the structural and biochemical organization, but also the function of the serotonergic system has been conserved during vertebrate evolution.

VIP-, enkephalin-, substance P- and somatostatin-like immunoreactivity in neurons intrinsic to the intestine: immunohistochemical evidence from organotypic tissue cultures

Small intestine from 18-day fetal mice grown for 3 weeks in organotypic tissue culture was found to contain numerous VIP, enkephalin, substance P and some somatostatin immunoreactive nerve fibers. Since these cultures should be devoid of all afferent or other extrinsic neuronal inputs, it is concluded that there are VIP, enkephalin, substance P and somatostatin containing neurons intrinsic to the intestinal wall. However, all 4 peptides may also be present in neurons originating outside the gastrointestinal tract as well as in the intrinsic neurons.

The precision of the conjunctival provocation test

Repeated conjunctiva] provocation tests ICPT) were done in 20 children with rhino‐conjunctivitis due to birch pollen allergy. Compared with the first open challenge, three successive blinded CPTs were reproducible within an allergen strength difference of one 10‐potency in 92 of the tests. Based on the data, a power function was constructed, making it possible to determine the number of patients needed to discriminate CRT sensitivity of a given magnitude between two populations. During the study period specific serum‐IgE increased in only three of 19 patients, indicating that stimulation of IgE antibody production is not a common consequence of repeated tests. We conclude that CPT is useful in clinical research. When indicated in clinical routine. CPT is a sale and easy test with good precision.

Hypoxic survival strategies in two fishes: extreme anoxia tolerance in the North European crucian carp and natural hypoxic preconditioning in a coral-reef shark

SUMMARY Especially in aquatic habitats, hypoxia can be an important evolutionary driving force resulting in both convergent and divergent physiological strategies for hypoxic survival. Examining adaptations to anoxic/hypoxic survival in hypoxia-tolerant animals may offer fresh ideas for the treatment of hypoxia-related diseases. Here, we summarise our present knowledge of two fishes that have evolved to survive hypoxia under very different circumstances. The crucian carp (Carassius carassius) is of particular interest because of its extreme anoxia tolerance. During the long North European winter, it survives for months in completely oxygen-deprived freshwater habitats. The crucian carp also tolerates a few days of anoxia at room temperature and, unlike anoxia-tolerant freshwater turtles, it is still physically active in anoxia. Moreover, the crucian carp does not appear to reduce neuronal ion permeability during anoxia and may primarily rely on more subtle neuromodulatory mechanisms for anoxic metabolic depression. The epaulette shark (Hemiscyllium ocellatum) is a tropical marine vertebrate. It lives on shallow reef platforms that repeatedly become cut off from the ocean during periods of low tides. During nocturnal low tides, the water [O2] can fall by 80% due to respiration of the coral and associated organisms. Since the tides become lower and lower over a period of a few days, the hypoxic exposure during subsequent low tides will become progressively longer and more severe. Thus, this shark is under a natural hypoxic preconditioning regimen. Interestingly, hypoxic preconditioning lowers its metabolic rate and its critical PO2. Moreover, repeated anoxia appears to stimulate metabolic depression in an adenosine-dependent way.

Temperature alters the respiratory surface area of crucian carp Carassius carassius and goldfish Carassius auratus

SUMMARY We have previously found that the gills of crucian carp Carassius carassius living in normoxic (aerated) water lack protruding lamellae, the primary site of O2 uptake in fish, and that exposing them to hypoxia increases the respiratory surface area of the gills ∼7.5-fold. We here examine whether this morphological change is triggered by temperature. We acclimated crucian carp to 10, 15, 20 and 25°C for 1 month, and investigated gill morphology, oxygen consumption and the critical oxygen concentration at the different temperatures. As expected, oxygen consumption increased with temperature. Also at 25°C an increase in the respiratory surface area, similar to that seen in hypoxia, occurred. This coincided with a reduced critical oxygen concentration. We also found that the rate of this transformation increased with rising temperature. Goldfish Carassius auratus, a close relative to crucian carp, previously kept at 25°C, were exposed to 15°C and 7.5°C. At 7.5°C the respiratory surface area of its gills was reduced by development of an interlamellar cell mass as found in normoxic crucian carp kept at 10-20°C. Thus, both species alter the respiratory surface area in response to temperature. Rather than being a graded change, the results suggest that the alteration of gill morphology is triggered at a given temperature. Oxygen-binding data reveal very high oxygen affinities of crucian carp haemoglobins, particularly at high pH and low temperature, which may be prerequisites for the reduced gill respiratory surface area at low temperatures. As ambient oxygen and temperature can both induce the remodelling of the gills, the response appears primarily to be an adaptation to the oxygen demand of the fish.