Biomedical subjects

Leena Tuomisto

Publications and source records attributed to Leena Tuomisto.

9 recordsLinked to original sources

PubMed2005

Synthesis and biological evaluation of 6/7-exo-methyl-3beta-(4-iodo)phenyltropane-2beta-carboxylic acid methyl esters.

6beta/7beta-Methyl-2-methoxycarbonyltropinones (3a, 3b) were synthesized and used as starting materials in the synthesis of 6beta/7beta-methyl-2beta-methoxycarbonyl-3beta-phenyltropanes (6a, 6b), 6beta/7beta-methyl-2beta-methoxycarbonyl-3beta-(4-iodo)phenyltropanes (7a, 7b) and 6beta-methyl-2beta-methoxycarbonyl-3beta-(4-iodo)phenylnortropane (8). The effect of 6/7-groups was evaluated by in vitro receptor binding to dopamine (DAT), serotonin (SERT) and norepinephrine (NET) transporters. Introduction of a methyl group at the 6- or 7-position diminished the overall affinity for the transporters, though mostly to NET. In vivo locomotor tests were performed in mice for compounds 7a and 8. Compound 8 had no apparent effect on locomotor activity. Compound 7a increased locomotion in a wide dose range, but was much less potent than a reference compound, 2beta-carbomethoxy-3beta-(4-iodo)phenyl-tropane (beta-CIT).

Animals↗

PubMed2004

Improving the quality of small animal brain pinhole SPECT imaging by Bayesian reconstruction.

The possibility of using existing hardware makes pinhole single-photon emission computed tomography (SPECT) attractive when pursuing the ultra-high resolution required for small animal brain imaging. Unfortunately, the poor sensitivity and the heavy weight of the collimator hamper the use of pinhole SPECT in animal studies by generating noisy and misaligned projections. To improve the image quality we have developed a new Bayesian reconstruction method, pinhole median root prior (PH-MRP), which prevents the excessive noise accumulation from the projections to the reconstructed image. The PH-MRP algorithm was used to reconstruct data acquired with our small animal rotating device, which was designed to reduce the rotation orbit misalignments. Phantom experiments were performed to test the device and compare the PH-MRP with the conventional Feldkamp-Davis-Kress (FDK) and pinhole ordered subsets maximum likelihood expectation maximisation (PH-OSEM) reconstruction algorithms. The feasibility of the system for small animal brain imaging was studied with Han-Wistar rats injected with (123)I-epidepride and (99m)Tc-hydroxy methylene diphosphonate. Considering all the experiments, no shape distortions due to orbit misalignments were encountered and remarkable improvements in noise characteristics and also in overall image quality were observed when the PH-MRP was applied instead of the FDK or PH-OSEM. In addition, the proposed methods utilise existing hardware and require only a certain amount of construction and programming work, making them easy to implement.

Algorithms↗

PubMed2004

Increased brain serotonin turnover correlates with the degree of shunting and hyperammonemia in rats following variable portal vein stenosis.

BACKGROUND/AIMS: Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of chronic liver disease. Brain monoamines have been implicated in the pathogenesis of HE. We examined the relationship between monoamine dysfunction and the degree of portal-systemic shunting (PSS) in rats with varying degrees of PSS. METHODS: Concentrations of catecholamines, serotonin, histamine, precursors and metabolites in frontal cortex of rats with varying degrees of PSS (9-99.8%) were measured by HPLC. RESULTS: The concentrations of the serotonin precursor, tryptophan, and its metabolite, 5-HIAA were increased up to 4-fold in brains of rats with various degrees of PSS and were significantly correlated with the degree of shunting and with arterial ammonia levels. Brain levels of histamine, its precursor, l-histidine, and metabolite, tele-methylhistamine were significantly increased only following total shunting. Concentrations of catecholamines and their metabolites were not significantly correlated with degree of PSS or hyperammonemia. CONCLUSIONS: Given the established role of the serotonin system in the regulation of sleep, circadian rhythmicity and locomotion these findings suggest that selective alterations of this system could be implicated in the pathogenesis of HE. Therapeutic approaches aimed at the normalization of serotonin turnover could be beneficial in the prevention and treatment of early neuropsychiatric symptoms of HE.

Animals↗

PubMed2004

Asthma Programme in Finland: high consensus between general practitioners and pulmonologists on the contents of an asthma referral letter.

AIMS: The purpose of the present study was to define quality criteria for an asthma referral letter using a national co-operative effort between general practitioners and pulmonologists. METHODS: A consensus-seeking expert panel representing primary and secondary health care merged evidence from the literature and existing national and local asthma programmes to produce 19 provisional criteria to be included in an asthma referral letter. These criteria were contained within a national questionnaire review which was sent out to groups of Finnish physicians. The target groups for the review were all chief pulmonologists in specialist care (n = 32), and representatives of all Finnish health centres (n = 283) - either the chief physician (n = 143) or the local asthma co-ordinating physician (n = 140). RESULTS: The overall response rate to the national questionnaire study was 75%. The three groups of responding physicians had very similar gradings on the necessity of the 19 provisional criteria, most of which were considered very necessary. 14 final disease-specific criteria for an asthma referral letter were derived as a result of this study. CONCLUSION: The main result of this study is an agreed data set of essential information that needs to be included in an asthma referral letter. Importantly these criteria were developed by general practitioners and pulmonologists together.

Journal Article↗

PubMed2003

Brain histamine and histamine H3 receptors following repeated L-histidine administration in rats.

In order to assess the importance of the chronic increase in precursor availability on central histaminergic mechanisms in rats, nine male Wistar rats received L-histidine orally at a dose of 1000 mg/kg, twice daily (07.00 h and 19.00 h) for 1 week; 9 rats were used as controls. Brain tissue histamine and tele-methylhistamine levels, as well as plasma histamine concentration were assayed. Binding properties and regional distribution of the autoregulatory histamine H3 receptors in brain were studied with [3H]-R-alpha-methylhistamine receptor binding and autoradiography. In L-histidine loaded rats, tissue histamine levels in cortex, hypothalamus, and rest of the brain were significantly increased by 40%-70%. Histamine concentrations in cerebellum and plasma, and tele-methylhistamine concentrations in cortex and hypothalamus did not change. The binding properties of H3 receptors in cortex were not altered. However, there were changes in the regional distribution of [3H]-R-alpha-methylhistamine binding sites, suggestive of a region-selective up-/down-regulation of histamine H3 receptors or their receptor sub-types. These results imply that following repeated L-histidine administration in the rat (1) there is enhanced synthesis of brain histamine not reflected in its functional release; (2) the excess of histamine is sequestered and stored rather than being metabolized; (3) histamine H(3) receptor binding properties are not altered, whereas receptor density is changed in selected regions. In conclusion, these results demonstrate that the neuronal mechanisms controlling histamine synthesis, storage, and release are adaptable and allow the sequestration of the excess of histamine in order to prevent excessively high neuronal activity.

Administration, Oral↗

PubMed2003

Increased concentrations of histamine and its metabolite, tele-methylhistamine and down-regulation of histamine H3 receptor sites in autopsied brain tissue from cirrhotic patients who died in hepatic coma.

BACKGROUND/AIMS: Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of chronic liver disease. To determine whether changes in the central histaminergic system are a feature of human HE, we studied histamine, tele-methylhistamine, and presynaptic autoregulatory H(3) receptors in cerebral cortex and caudate-putamen obtained at autopsy from six cirrhotic patients and six appropriately matched controls. METHODS: Histamine was assayed by HPLC; tele-methylhistamine by GC-MS. H(3) receptors were studied by in vitro receptor binding using [3H]R-alpha-methylhistamine as ligand. RESULTS: In HE patients, there was a significant fourfold increase of histamine in caudate-putamen and a significant increase in all cortical regions studied. tele-Methyhistamine was also increased and the densities of histamine H(3) receptor sites were significantly decreased in patient material. CONCLUSIONS: These findings are consistent with activation of the histaminergic system in HE. Given that histamine participates in the regulation of arousal and circadian rhythmicity, they indicate that induction of central histamine mechanisms may contribute to the development of neuropsychiatric symptoms, such as sleep disturbances and altered circadian rhythms in chronic HE and suggest that pharmacological manipulation of the histaminergic system could be beneficial in the treatment of HE in chronic liver failure.

Adult↗

PubMed2002

Local lactate and histamine changes in small bowel circulation measured by microdialysis in pig hemorrhagic shock.

Hemorrhagic shock results in inadequate tissue oxygenation. Plasma lactate (L) can characterize the degree of systemic oxygen debt (OD), but gives no information on local changes. The aim of this study was to characterize different degrees of hemorrhagic shock by microdialysis measurement of L and histamine (H) in small bowel circulation. Thirty-eight pigs were randomized to five groups of increasing OD (< 50 --> 120 ml/kg). The OD was accrued by hemorrhage over 60 min and was followed by retransfusion and observation for 3 days. In parallel to plasma probes, subserosa(ss)-, submucosa(sm)-, and intraluminal(il)-L- and H-probes were obtained by small bowel microdialysis every 30 min for 210 min. Ss- and sm-L increased during hemorrhage from 1.2 +/- 0.06 and 1.18 +/- 0.06 to 2.57 +/- 0.15 and 2.96 +/- 0.27 mmol/L. Highest mean L > 3.5mmol/L resulted 90 and 120 min after induction of hemorrhage. Although ss- and sm- levels hardly differed, il-L was significantly decreased with 0.27 +/- 0.02 mmol/L at 0 min and highest mean il-L at 120 min: 2.45 +/- 0.51 mmol/L. Sm-L was significantly increased after 60, 90, 120, and 150 min of highest hemorrhage severity (OD > 100 mL/kg). In parallel, systemic L increased significantly during hemorrhage and correlated well with the severity of shock. Although systemic H increased significantly during hemorrhage (from 1.3 +/- 0.31 to 15.2 +/- 0.67 ng/mL), H-dialysates showed no effect either over time nor with the degree of hemorrhage. In conclusion, microdialysis allows evaluation of local L changes in small bowel circulation in pig hemorrhagic shock. Sm-L levels appear to correlate with the degree of shock. Local H changes were not observed during hemorrhagic shock in this study.

Animals↗

PubMed2002

EEG noise cancellation by a subspace method based on wavelet decomposition.

BACKGROUND: Noise reduction techniques play an essential role in EEG signal processing applications. A variety of methods are currently in use, including those based on linear filtering and adaptive noise cancellation, as well as subspace-based methods using singular value decomposition (SVD). SVD offers a robust method to decompose the data matrix into signal and noise subspaces. However, the SVD algorithm is characterized by high computational complexity, which restricts its use in real time EEG signal analysis. MATERIAL/METHODS: In this work we applied a wavelet transform to decompose the EEG signal into parallel subsignals. Noise was cancelled using the SVD-based method for each subsignal, and the noiseless EEG was reconstructed by using an inverse wavelet transform. EEGs were recorded in freely behaving rats from two different sites of the brain: 1). the hilar region of the dentate gyrus of the hippocampus, 2). the frontal cortex, with the electrode tip located in the vicinity of the epipial neocortical surface. RESULTS: Our noise suppression method had the most obvious effect on the EEG frequency spectrum, where random noise was considerably diminished. In the time domain, the reconstructed waveform closely resembled the original EEG signal, but it could clearly be seen that most of the transient spikes had been removed. CONCLUSIONS: The present method offers remarkable computational savings and is especially well adapted for the analysis of highly dynamic EEGs.

Algorithms↗

PubMed1987

Differential effect of tetracaine and bupivacaine on catecholamine and 5-hydroxytryptamine turnover.

The effect of the local anesthetics, tetracaine and bupivacaine, on monoamine oxidase (MAO) activity of rat brain and on the major steps of catecholamine and 5-hydroxytryptamine (5-HT) turnover was examined. The IC50 of tetracaine for MAO-A and MAO-B inhibition was 1.2 microM and 19.5 microM, respectively. Up to 2.5 mM bupivacaine was without effect on either form of MAO. None of the following activities in rat brain or adrenal medulla were inhibited by 5-2500 microM of tetracaine or bupivacaine: catecholamine-O-methyltransferase, tyrosine hydroxylase, dopamine-beta-hydroxylase. Tetracaine caused only a moderately potent inhibition of synaptosomal uptake of norepinephrine (NE) (IC50 14 microM), dopamine (IC50 37 microM) and 5-HT (IC50 45 microM). The potent and specific MAO inhibition by tetracaine, in association with an impaired uptake of synaptosomal amines, may lead to an increase in the synaptosomal content of neurotransmitter amines, such as 5-HT and NE, with possible antinociceptive consequences.

Animals↗