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Biomedical subjects

E Lindgren

Publications and source records attributed to E Lindgren.

At least 19 recordsLinked to original sources
PubMed2001

Tick-borne encephalitis in Sweden and climate change.

BACKGROUND: The incidence of tick-borne encephalitis (TBE) in Sweden has substantially increased since the mid-1980s. During the same period the climate has become milder and ticks have become more abundant. We investigated whether there is a link between the change in climate and the increase in incidence of TBE. METHODS: Since the late 1950s all cases of encephalitis admitted in Stockholm County have been serologically tested for TBE. We analysed the period 1960-98 with multiple regressions. The number of days per season with temperatures of known importance for tick prevalence and pathogen transmission were studied. 2 years of temperature data were related to each TBE incidence rate to account for the tick's long life-span. FINDINGS: Increases in disease incidence was significantly related (R(2)=0.58; p<0.0001) to a combination of two consecutive mild winters, temperatures favouring spring development (8-10 degrees C) and extended autumn activity (5-8 degrees C) in the year prior to the incidence year, and temperatures allowing tick activity (5-8 degrees C) early in the incidence year. INTERPRETATIONS: The findings indicate that the increase in TBE incidence since the mid-1980s is related to the period's change towards milder winters and early arrival of spring. Other factors may have influenced TBE incidence such as more people in endemic locations, and increases in host animal populations; factors which are partly climate related. Access to TBE vaccination since 1986 and increased awareness of ticks might have caused an underestimation of the links found. Our findings also suggest that the incidence of other tick-borne zoonoses might have been affected by the milder climate.

Animals↗
PubMed2000

Impact of climatic change on the northern latitude limit and population density of the disease-transmitting European tick Ixodes ricinus.

We examined whether a reported northward expansion of the geographic distribution limit of the disease-transmitting tick Ixodes ricinus and an increased tick density between the early 1980s and mid-1990s in Sweden was related to climatic changes. The annual number of days with minimum temperatures above vital bioclimatic thresholds for the tick's life-cycle dynamics were related to tick density in both the early 1980s and the mid-1990s in 20 districts in central and northern Sweden. The winters were markedly milder in all of the study areas in the 1990s as compared to the 1980s. Our results indicate that the reported northern shift in the distribution limit of ticks is related to fewer days during the winter seasons with low minimum temperatures, i.e., below -12 degrees C. At high latitudes, low winter temperatures had the clearest impact on tick distribution. Further south, a combination of mild winters (fewer days with minimum temperatures below -7 degrees C) and extended spring and autumn seasons (more days with minimum temperatures from 5 to 8 degrees C) was related to increases in tick density. We conclude that the relatively mild climate of the 1990s in Sweden is probably one of the primary reasons for the observed increase of density and geographic range of I. ricinus ticks.

Animals↗
PubMed1998

Epidemiology of trichinellosis in lynx in Finland.

Three hundred and twenty seven European lynx (Lynx lynx) were examined for Trichinella sp. larvae using the muscle digestion method. The animals were of both sexes, various ages, and collected between 1989 and 1994 in different locations in Finland. Forty percent of them (132) were found to be infected. Infection was overdispersed, so that the majority of infected lynx only harboured small amounts of larvae, while a minority had higher densities of infection, but never significantly exceeding 40 larvae per gram of muscle (lpg). The median density of infection was 1.04 lpg. To find factor statistically associated with the risk of infection, multivariate logistic regression analysis was performed. Male sex, increasing age, and the density of raccoon dog population in the area were all significantly associated with infection. However, the association with age was not linear and prevalence did not increase after middle age. The mean density of infection decreased slightly with age. The association with the density of the raccoon dog population leads to a tentative hypothesis that the raccoon dog might be an important reservoir of sylvatic trichinellosis in Finland.

Age Distribution↗
PubMed1997

Combination neurohormonal blockade with ACE inhibitors, angiotensin II antagonists and beta-blockers in patients with congestive heart failure: design of the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study.

BACKGROUND: The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study is a trial of combination neurohormonal blockade using an angiotensin II antagonist (candesartan), an angiotensin-converting enzyme inhibitor (enalapril) and a beta-blocker (metoprolol) in patients with congestive heart failure (CHF). OBJECTIVES: Primary objectives of stage I are to determine the efficacy (via the 6 min walk test) and safety of candesartan alone, and in combination with enalapril, versus enalapril alone. Secondary objectives are to determine the effect of the above combinations on neurohormones, ventricular function, quality of life and symptoms. Stage II objectives are similar, evaluating the effect of the addition of metoprolol or placebo to the above medication(s). DESIGN: Randomized, two-stage trial consisting of a three-way comparison (stage I), followed by a 3 x 2 partial factorial design (stage II). SETTING: Sixty out-patient clinics in five countries. PATIENTS: Patients with symptoms of CHF (New York Heart Association functional classes II to IV), ejection fraction less than 40% and 6 min walk distance of 500 m or less. INTERVENTIONS: In stage I, 770 patients are randomized to receive candesartan alone, enalapril alone, or candesartan plus enalapril. After five months (end of stage I), patients are assessed for eligibility to be randomized in stage II. Those who are not candidates for randomization to beta-blocker or placebo are followed on their stage I medications until the end of the study. In stage II, patients are randomized to receive metoprolol or placebo for a further six months in addition to their stage I medications. Endpoints are measured at baseline, end of stage I (week 20) and end of stage II (week 46). STUDY STATUS: The study has recently completed follow-up in both stages. The findings from this study will be used to design a large scale mortality study that will help further define the role of neurohormonal blockade in patients with CHF.

Adrenergic beta-Antagonists↗
PubMed1996

Kinetics of cell-wall digestion of orchardgrass and alfalfa silages treated with cellulase and formic acid.

The objectives of this study were to determine the effects of cellulase (from Trichoderma longibrachiatum) combined with formic acid, applied before ensiling, on the subsequent concentration and composition of the cell wall and on the extent and rate of in situ cell-wall digestion of orchardgrass (Dactylis glomerata L.) and alfalfa (Medicago sativa L.). Treated and control forages of both plant species were ensiled for at least 60 d before being ruminally digested by two fistulated cows. Analyses of NDF, ADF, and acid detergent lignin were conducted sequentially on original and digested samples. Data were fitted with a first-order, nonlinear model to estimate extents and rates of digestion of potentially digestible NDF, cellulose, and hemicellulose. The concentration of indigestible residue and the discrete lag time before digestion were also determined for the cell-wall components. After ensiling, the mean NDF concentration of treated silages was 19% lower than that of control silages; the effect was greater for orchardgrass than for alfalfa. The extent of digestion of NDF, cellulose, and hemicellulose, respectively, was 33, 37, and 27% lower for treated silages than for control silages. Treatment effects on the extent of digestion varied between plant species. Cellulose from treated orchardgrass was digested 19% more slowly than cellulose from the control silage. Indigestible residue concentrations of NDF, cellulose, and hemicellulose, respectively, were 7, 8, and 7% lower in treated silages than in control silages. Thus, extensive cell-wall degradation by cellulase during ensiling resulted in less digestible cell-wall material for ruminal digestion but greater total cell-wall degradation, including that during ensiling and ruminal incubation, especially during early digestion in the rumen.

Cell Wall↗
PubMed1993

A survey of mineral status of soils, feeds and cattle in the Selale Ethiopian highlands. I. Macro elements.

The macro mineral status of cattle in the Selale highlands of Ethiopia was evaluated during the rainy and dry seasons of 1989 and 1990 in terms of mineral concentrations in soils, feeds, blood plasma and faeces on 25 farms. Bone samples from animals of local breeds from a slaughter house were collected during the rainy and dry seasons of 1990. Soils were analysed for pH, organic matter, Ca, P, Mg, Na and K. The results indicated wide variation in the concentrations of minerals on different farms. Available feeds in the area consist of pasture, hay, the straw of barley, oats and teff, and the grains of barley and oats. Pasture grass and other feeds were found to be deficient in Na, P and Mg in relation to dietary requirements. Analyses of blood plasma from crossbred and local cattle showed that a number of samples contained P below the critical level of 1.45 mmol/litre. Effects of year and season were significant for Ca, P, Mg and K. The effect of age was significant for P (P < 0.001). Faecal analyses revealed that about 80% of animals were deficient in Na. Wide variations in the mineral content of soils and lack of significant correlations among soil, pasture and blood plasma indicated that soil and pasture analyses are not reliable in assessing macro mineral status of grazing cattle in this environment. Analyses of bone and blood for Ca and P, blood for Mg and faeces for Na appear to provide better indices.

Animal Feed↗
PubMed1993

A survey of mineral status of soil, feeds and cattle in the Selale Ethiopian highlands. II. Trace elements.

The trace element status of crossbred Friesian x zebu (Boran) and local zebu cattle in the Selale highlands of Ethiopia was evaluated during the rainy and dry seasons of 1989 and 1990 in terms of the trace element content of soils, feeds, blood plasma and faeces on 25 randomly selected farms. Liver samples from animals of local breeds from a slaughter house were collected during the rainy and dry seasons of 1990 and analysed. Soil Fe and Mn were found to be high. Iron contents of all feeds were extremely high and Mn contents were higher than the dietary requirement. A large proportion of feed samples were deficient in Cu and zinc. There were wide variations in the concentrations of these elements among the soil and feed samples. Blood plasma Fe (P < 0.001) and Cu (P < 0.01) values differed significantly between the years. Plasma samples collected during 1990 contained lower mean Cu than 1989. The effect of season was statistically significant (P < 0.001) for all the trace elements. More than half of the animals were found to have low plasma Cu and Zn during the rainy season. Due to lack of any correlations between soil, pasture and blood plasma it is suggested that analyses of soils and pasture are not reliable for assessing the Fe, Cu and Zn status of grazing cattle in the highlands. Analyses of liver and blood appear to provide better indices.

Animal Feed↗
PubMed1991

Insulin-like growth factor I shifts from promoting cell division to potentiating maturation during neuronal differentiation.

SH-SY5Y neuroblastoma cells undergo neuronal differentiation and their proliferation is inhibited when they are treated with phorbol 12-myristate 13-acetate (PMA). Insulin and insulin-like growth factor I (IGF-I) are mitogens for the nontreated SH-SY5Y cells, whereas the proliferative response to such factor stimulation is lost upon differentiation, in spite of the fact that the receptors for insulin and IGF-I remain expressed and functional in the differentiated cells. Here we show that the PMA-induced differentiation of SH-SY5Y cells grown in a serum-free medium is strongly potentiated by nanomolar concentrations of IGF-I, as judged by morphology and markers for neuronal differentiation--e.g., neuropeptide tyrosine and growth-associated protein 43. Also, insulin and IGF-II potentiated the phorbol ester-induced differentiation, although less efficiently than IGF-I. Using blocking anti-receptor antibodies, it could be shown that the differentiation induced by these factors, in combination with PMA, was primarily mediated through the IGF-I receptor.

Blotting, Northern↗
PubMed1988

Protein kinase C activation increases noradrenaline release from the rat hippocampus and modifies the inhibitory effect of alpha 2-adrenoceptor and adenosine A1-receptor agonists.

We have studied the effect of stimulating protein kinase C with phorbol esters on the release of [3H]-noradrenaline (NA) in the absence or presence of presynaptic alpha 2-adrenoceptor blocking agents and compared that to the elevation of cyclic AMP levels more than 10-fold by a combination of rolipram and forskolin. 4-beta-Phorbol 12,13-dibutyrate (PDiBu) increased stimulated (3 Hz) [3H]-NA release markedly and in a concentration dependent manner. 4-alpha-Phorbol-12,13-didecanoate was ineffective. The effect of PDiBu was not significantly reduced by nifedipine (1 microM), but was proportionally less in the presence of an alpha 2-adrenoceptor antagonist, yohimbine. PDiBu inhibited the presynaptic effect of alpha 2-adrenoceptor agonists clonidine and UK 14304. By contrast, the presynaptic effect of the adenosine analogue R-PIA was not reduced by PDiBu. PDiBu caused an increase in cyclic AMP that depended on adenosine receptor stimulation. Elevation of cyclic AMP had a limited effect on NA release from rat hippocampus, and did not significantly decrease the presynaptic inhibitory effect of UK 14304 (0.1 microM), of morphine (1 microM) or of the adenosine A1-receptor agonist CHA (1 microM). The effect of phorbol esters and several presynaptic inhibitors of NA-release in the rat hippocampus cannot be explained by changes in cyclic AMP levels in the tissue. Phorbol esters that stimulate protein kinase C appear to interact with a target that is the site of action alpha 2-adrenoceptors in this tissue. This site is not a dihydropyridine sensitive Ca-channel and is also different from the target of presynaptic adenosine receptors. Thus, activation of protein kinase C discriminates between apparently similar presynaptic mechanisms.

Animals↗
PubMed1987

Interaction of dihydropyridine calcium channel agonists and antagonists with adenosine receptors.

We have confirmed our previous (Fredholm et al. 1986a) finding that the dihydropyridine calcium channel agonist Bay K 8644 can displace [3H]-R-PIA from its binding site, the adenosine A1-receptor. Bay K 8644 had an apparent Ki of 5.2 X 10(-6) M. The effect was shared by the two dihydropyridine calcium channel antagonists nifedipine and felodipine (Ki 4.2 and 8.7 X 10(-6) M, respectively). By contrast, two non-dihydropyridine calcium channel antagonists, verapamil and diltiazem, did not affect binding. Bay K 8644 displaced [3H]-R-PIA from its binding sites in a solubilized preparation. [3H]-XAC, a novel, potent A1-receptor antagonist ligand, was also displaced by the dihydropyridine compounds with a similar or slightly higher potency as the displacement of R-PIA. This suggests a direct interaction with the adenosine receptor rather than an effect on regulatory GTP-binding proteins. However, at 1 mumol/l neither Bay K 8644 nor nifedipine significantly attenuated cyclic AMP accumulation in rat hippocampi or the R-PIA-mediated adenylate cyclase inhibition. The results show that dihydropyridine compounds that act as agonists or antagonists on L-type calcium channels can also affect adenosine receptors. The potency of the compounds for this effect is much lower than their potency as calcium channel agonists or antagonists. The results may therefore be of more experimental than clinical significance.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1987

Effects of N-ethylmaleimide and forskolin on noradrenaline release from rat hippocampal slices. Evidence that prejunctional adenosine and alpha-receptors are linked to N-proteins but not to adenylate cyclase.

N-ethylmaleimide (NEM) treatment has been shown to inactivate regulatory GTP-binding N (G)-proteins in many preparations, including slices of rat hippocampus. NEM-treatment (100 microM for 15 min) has been used to examine the possible involvement of a N-protein in the prejunctional inhibitory effect of an adenosine analogue, R-PIA acting on A1-receptors, and of clonidine acting on alpha 2-adrenoceptors in this tissue. NEM treatment significantly enhanced basal overflow of [3H]NA and the overflow stimulated by low (0.3 Hz) frequency stimulation, but not the overflow stimulated by higher (1-10 Hz) frequency stimulation. The prejunctional inhibitory effect of R-PIA (1 microM) on NA release, stimulated by a 3 Hz stimulation, was abolished by NEM pretreatment, which also eliminated the dose-dependent prejunctional effect of clonidine and reduced the facilitatory effect of yohimbine. Forskolin had a small, but significant stimulatory effect on NA overflow, but did not reduce the prejunctional inhibitory effect of R-PIA. The adenylate cyclase inhibitor SQ 22, 536 did not reduce NA overflow. These results show that NEM blocks a critical step in the prejunctional action of both adenosine- and alpha 2-receptor agonists, which may be a N-protein. The possibility is discussed that the prejunctional A1- and alpha 2-receptors couple to a N-protein that controls a different effector than adenylate cyclase.

Adenylyl Cyclases↗
PubMed1987

Alpha-adrenoceptor stimulation, but not muscarinic stimulation, increases cyclic AMP accumulation in brain slices due to protein kinase C mediated enhancement of adenosine receptor effects.

In the present study, using rat hippocampal slices, we have further examined the stimulatory effect of alpha 1-adrenoceptors on the accumulation of cyclic AMP, which is known to depend on calcium and adenosine. The addition of noradrenaline (NA) stimulated the accumulation of [3H]inositol phosphates in [3H]inositol-treated slices. This effect was shared by carbachol (10-100 mumol l-1) but not by the adenosine receptor agonist 2-chloroadenosine (100 mumol l-1). The stimulatory effect of the alpha-agonists (phenylephrine or NA + propranolol) on cyclic AMP was shared by a diacylglycerol derivative, sn-1-oleyl-2-acetyl glycerol (OAG), and by the tumour-promoting phorbol esters phorboldibutyrate (PDiBu) and tetradecanoyl phorbol acetate (TPA). PDiBu caused a translocation of protein kinase C from soluble to particulate fractions. The effects of PDiBu and alpha-adrenoceptor stimulation on cyclic AMP were not additive. Surprisingly, carbachol (1-1000 mumol l-1) did not stimulate cyclic AMP accumulation in rat hippocampal slices either in the presence or in the absence of an adenosine receptor agonist. The results are compatible with the opinion that alpha-adrenoceptor stimulating drugs enhance the formation of inositol phosphates and diacylglycerol, which synergistically activate protein kinase C, which in turn augments the stimulation of cyclic AMP formation. Thus, a neurotransmitter whose principal biological effect is to stimulate inositol phosphate formation can influence cyclic AMP formation by virtue of an interaction with the actions of the ubiquitous neuromodulator adenosine. The fact that the effect of the alpha-receptor stimulation was not mimicked by a muscarinic agonist could indicate that other factors besides activation of inositol phospholipid hydrolys are important for this receptor-receptor interaction.

Adrenergic alpha-Agonists↗
PubMed1986

Effects of N-ethylmaleimide and forskolin on glutamate release from rat hippocampal slices. Evidence that prejunctional adenosine receptors are linked to N-proteins, but not to adenylate cyclase.

In the present experiments we have examined the effect of N-ethylmaleimide (NEM) on the release of [3H]glutamate from rat hippocampal slices. Pretreatment of slices with NEM in a concentration between 50 microM and 200 microM, can inhibit the GTP-binding protein (Ni) that transmits receptor signals into inhibitions of adenylate cyclase, without affecting the Ns-protein, that transmits signals into stimulation of the cyclase, or the cyclase. The adenosine receptor agonist R-phenylisopropyladenosine (R-PIA, 1 microM) caused an approximately 50% inhibition of the evoked [3H]glutamate release. This effect was completely prevented by NEM treatment, which did not affect basal or stimulated release of the amino acid. By contrast, the effect of R-PIA was unaffected by adding an adenylate cyclase stimulator (forskolin 1 microM) and a phosphodiesterase inhibitor (rolipram, ZK 62.711, 30 microM) which raised the cyclic AMP content of the slices approximately 10-fold. In conclusion, these results suggest that the adenosine receptor that mediates prejunctional inhibition of glutamate release is coupled to a protein similar to the Ni-protein, but that another effector than adenylate cyclase is involved.

Adenylyl Cyclases↗