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1.
Markku Walamies Vesa Virtanen Matti Koskinen Arto Uusitalo 《European journal of nuclear medicine and molecular imaging》1994,21(9):968-972
The decrease in mortality among patients receiving thrombolytic therapy for myocardial infarction is greater than would be expected from the improvement in left ventricular contractile function alone; thus some additional advantage of recanalization of the infarctrelated coronary artery probably exists. Changes in the post-infarction myocardial metabolic state with respect to artery patency have not been studied with a gamma camera previously. A single-photon emission tomography scan using the fatty acid analogue para-123I-iodophenylpentadecanoic acid was performed at rest before hospital discharge on nine patients with first anterior myocardial infarction. All patients had received intravenous thrombolytic therapy at the beginning of the insult. The semiquantitative analysis of the left ventricle included a total of 44 segments in each patient. The test was repeated 3 months later, with the patients divided into two groups: six patients had an angiographically patent left anterior descending coronary artery (group A), and three an occluded artery (group B). In group A the number of myocardial segments with abnormal (<70% of maximum) fatty acid uptake was initially 20.2±4.7 (mean±SD) and was reduced to 11.3±6.1 during the follow-up (95% confidence interval of the decrease 16.0–1.7 segments). In group B the number of these aberrant segments was fairly constant (21.7±13.1, initial test, and 21.3±13.3, retest). Our preliminary results suggest that even when thrombolytic therapy fails to prevent myocardial infarction, myocardial fatty acid metabolism has a better change of recovering if the relevant coronary artery has regained its patency. This finding emphasizes the need for further study to establish whether a direct link exists between myocardial metabolic state and patient survival after infarction. 相似文献
2.
Markku Leino MD Kalevi Pyörälä Seppo Lehto Arto Rantala 《Documenta ophthalmologica. Advances in ophthalmology》1992,80(4):309-315
Lens opacity studies were performed using an electronic Lens Opacity Meter (Interzeag Opacity Lensmeter 701) in a population (n = 321) with ischaemic heart disease. These patients are participating in a trial targetting at the reduction of mortality and incidence of myocardial infarction using a cholesterol-lowering drug, simvastatin. A separate study to evaluate the reliability of the method showed good reproducibility. Repeated measurements after a short time-interval (2–10 days) gave statistically lower opacity values either due to a change in lens transparency or perhaps a change in pigment and cell dispersion in the acqueous caused by repeated mydriasis. Lens opacity values showed a highly significant positive correlation to age. Serum cholesterol, systolic blood pressure and smoking habits showed no significant correlations to the levels of lens opacity when adjustments for age were made.Abbreviations HMG-CoA
hydroxy-methylglutarylcoenzyme A
- 4S
Scandinavian Simvastatin Survival Study
- LOM
lens opacity meter 相似文献
3.
Arto J. Turunen José A. Fernández Leena Lindgren Kaija T. Salmela Lauri E. Kyllönen Heikki Mäkisalo John H. Griffin Sanna M. Siitonen Jari Petäjä Eero J. Pesonen 《American journal of transplantation》2005,5(9):2204-2212
We studied the role of endogenous activated protein C (APC), the major physiological anti-coagulant with concomitant anti-inflammatory properties, on ischemia/reperfusion (I/R) in 45 patients participating in a larger trial comparing three immunosuppressive protocols in cadaveric renal transplantation: perioperative anti-thymocyte globulin (ATG, Fresenius AG, Bad Homburg, Germany), perioperative basiliximab and conventional triple therapy. Blood samples for assessing plasma APC, protein C, and lactoferrin concentrations, neutrophil CD11b and L-selectin expressions and blood leukocyte differential counts were obtained preoperatively and before reperfusion from central venous cannula, complemented with simultaneous samples from iliac artery and graft vein for calculation of transrenal differences (Delta) of study parameters at 1 and 5 min after reperfusion. Unlike basiliximab or conventional therapy groups, ATG infusion induced a substantial increase in plasma APC concentration (119 [88-144]% before infusion vs. 232 [85-1246]% after infusion, p<0.001), resulting in renal graft sequestration of APC at 1 min after reperfusion (Delta=-72 [-567 to 12]%, p<0.001). Graft APC consumption was associated with transrenal reduction of neutrophil activation markers (L-selectin r=0.7, p=0.01; lactoferrin r=-0.6, p=0.02; CD11b r=-0.8, p=0.001), and with both warm (r=0.6, p=0.01) and cold ischemia time (r=0.6, p=0.02) and donor age (r=0.6, p=0.01). These findings suggest that APC has an anti-inflammatory role in I/R injury in clinical renal transplantation. 相似文献
4.
We have earlier introduced a principle for learning metrics, which shows how metric-based methods can be made to focus on discriminative properties of data. The main applications are in supervising unsupervised learning to model interesting variation in data, instead of modeling all variation as plain unsupervised learning does. The metrics are derived by approximations to an information-geometric formulation. In this paper, we review the theory, introduce better approximations to the distances, and show how to apply them in two different kinds of unsupervised methods: prototype-based and pairwise distance-based. The two examples are self-organizing maps and multidimensional scaling (Sammon's mapping). 相似文献
5.
This study examined the phenomenon of acute tolerance to ethanol (ETOH) using drug discrimination learning (DDL), and open-field (OF) procedures. In DDL, rats were trained to discriminate between ETOH (1.2 g/kg) and saline. Doses of ETOH lower (0.6 and 0.9 g/kg), or higher (1.8 and 2.4 g/kg) than the training dose were tested to examine possible influence of ETOH pretreatment doses on the expression of acute tolerance. To assess concentrations of ETOH in the organism, a rebreathed air procedure was used. Equal concentrations after different ETOH doses were achieved by postponing the tests until sufficient time had elapsed. Only doses of ETOH higher than the training dose produced acute tolerance in the DDL procedure. For the response-time data no acute tolerance was observed. In the OF experiment, the occurrence of acute tolerance was examined for different spontaneous behaviours in drug-naive animals. At equal ETOH concentrations, the group examined during the descending phase of intoxication (1.8 g/kg, 60 min post-injection), reared significantly more than the group tested during the ascending phase (1.5 g/kg, 10 min post-injection). Other OF behaviours did not differ significantly between the two time intervals. Thus, it is suggested that acute tolerance is seen both in ETOH naive and in ETOH pre-exposed rats. However, in DDL acute tolerance was observed only when doses higher than the training dose of ETOH were evaluated. 相似文献
6.
Juha P Ahtiainen Arto Pakarinen William J Kraemer Keijo H?kkinen 《Revue canadienne de physiologie appliquée》2004,29(5):527-543
The aim of the present study was to investigate acute hormonal and neuromuscular responses and recovery in strength athletes versus nonathletes during heavy resistance exercise performed with the forced and maximum repetitions training protocol. Eight male strength athletes (SA) with several years of continuous resistance training experience and 8 physically active but non-strength athletes (NA) volunteered as subjects. The experimental design comprised two loading sessions: maximum repetitions (MR) and forced repetitions (FR). MR included 12-RM squats for 4 sets with a 2-min recovery between sets. In FR the initial load was higher than in MR so that the subject could lift approximately 8 repetitions by himself and 4 additional repetitions with assistance. Before and after the loading protocols, blood samples were drawn to determine serum testosterone, free testosterone, cortisol and growth hormone concentrations, and blood lactate. Maximal voluntary isometric force and EMG activity of the leg extensors was measured before and after the loading as well as 24 and 48 hrs after the loading. The concentrations of the hormones measured increased significantly (p < .01-.001) after both loadings in both groups. The responses tended to be higher in FR than the MR loading and the increases of testosterone concentrations were significantly (p < .01) greater in both loadings in SA than in NA. Both loading protocols in both groups also led to neuromuscular fatigue observable with significant acute decreases in isometric strength by 32-52% (p < .001) and in maximal iEMG (p < .05-01) associated with large increases in blood lactate. These data suggest that, at least in experienced strength athletes, the forced-repetition protocol is a viable alternative to the more traditional maximum-repetition protocol and may even be a superior approach. 相似文献
7.
Markku Walamies Matti Koskinen Arto Uusitalo Kari Niemelä 《The International Journal of Cardiac Imaging》1994,10(2):123-129
Myocardial metabolism in exercise was determined by studying 21 syndromeX patients and 14 healthy volunteers with an aromatic fatty acid analogue IPPA and a gamma camera. We developed criteria for visual semiquantitative assessment of relative segmental radiotracer uptake and washout, and tested a new computer program for quantitative evaluation. One volunteer (7%) and 12 patients (57%) showed visually inhomogeneous uptake (p=0.006, 2-test) in SPECT polar tomograms after a maximal ergometry test. Images in none of the volunteers and seven patients (33%) gave the impression of a slowed regional washout (p=0.057). Only six patients (29%) had a normal radial polarogram. Patients with irregular coronary angiograms (showing slow flow or minor sclerosis) and those with chest pain during the IPPA exercise test had a very low frequency of normalcy, but this was not significant.Total washout was higher in patients than in the reference population, as the exercise to rest activity ratio was 1.36 SD 0.13 versus 1.25 SD 0.11 in computerized quantitation (p=0.015, t-test). Washout did not correlate with age, sex or exercise heart rate. Regarding computerized analysis of uptake and slow washout, the number of deviant segments was not significantly higher in patients than in reference population. Semiquantitative and quantitative analysis correlated in the assessment of uptake, but not in the assessment of washout. Possible reasons for the discrepancy are discussed.Conclusions of this study are not straightforward. SyndromeX was associated with inhomogeneous IPPA uptake, which is not at variance with the theory of microvascular dysfunction. On the other hand, the analysis of washout presumably implies higher fatty acid utilization in patients than in normal controls, which is not a characteristic phenomenon in myocardial ischemia. 相似文献
8.
Purpose. The effects of 2-hydroxypropyl--cyclodextrin (HP--CD) on the aqueous solubility and stability of two lipophilic bispilocarpine prodrugs were investigated at pH 7.4.
Methods. The solubility of prodrugs was studied by phase-solubility method (0–72.5 mM HP--CD). The stability of one of the prodrugs was investigated as a function of temperature (40°C–70°C) and HP--CD concentration (0–72.5 mM). The apparent rate constants (k
1, k
2) for degradation of prodrug in 1:1 and 1:2 inclusion complexes and apparent stability constants (K
1:1, K
l:2) were calculated by the curve-fitting method.
Results. The phase-solubility diagrams were classified as Ap-type and the apparent stability constants (K
l:l, K
l:2) for 1:1- and 1:2-inclusion complexes were calculated to be 143–815 M–l and 29–825 M–1, respectively. The stability of prodrug increased as a function of HP--CD concentration over the studied temperature range. The shelf-life (t
90%, calculated by the Arrhenius equation) of the prodrug in 72.5 mM HP--CD solution increased 5.1-fold and 6.1-fold at 25°C and 4°C, respectively.
Conclusions. The solubility of the prodrugs was shown to increase markedly in phase-solubility studies. The degradation rate of prodrug in stability studies was shown to be slower in the l:2-complex than in the l:l-complex and the relative amounts of complex species were found to be dependent on CD concentration. 相似文献
9.
Pennanen Niina Lapinjoki Seppo Urtti Arto Mönkkönen Jukka 《Pharmaceutical research》1995,12(6):916-922
Purpose. In order to evaluate the possible antiinflammatory action of bisphosphonates, the effect of the drugs on the secretion of proinflammatory cytokines (IL-l, IL-6 and TNF) from macrophages was studied. Liposomes or high concentration of extracellular calcium was used to enhance the intracellular delivery of bisphosphonates.
Methods. RAW 264 cells were used as macrophage model, and they were induced with lipopolysaccharide to produce the cytokines. The cytokine concentrations in the culture supernatants were measured with time-resolved fluoroimmunoassay.
Results. As a free drug, clodronate and pamidronate, but not etidronate, inhibited LPS-stimulated secretion of the cytokines from macrophage-like RAW 264 cells. Low concentrations of pamidronate, however, induced the IL-6 secretion, and the cytokine inhibitory action at the higher concentrations of pamidronate was attributed to cytotoxicity of the compound. The cytokine induction or toxic effects were not observed with clodronate or etidronate. When the drugs were encapsulated in negatively charged unilamellar liposomes, the inhibitory potency of both clodronate and etidronate enhanced by a factor of 10-20, while that of pamidronate was not increased. The complex formation of bisphosphonates with extracellular calcium, although enhancing the uptake of the compounds by macrophages, did not considerably increase their cytokine inhibitory potency.
Conclusions. Bisphosphonates have inhibitory action on cytokine secretion by macrophages. The non-cytotoxic cytokine inhibition by liposome encapsulated clodronate could be beneficial in local inflammatory diseases, where the inflammation is sustained by the excessive amounts of inflammatory cytokines produced by activated macrophages. 相似文献
10.
Suhonen Pekka Järvinen Tomi Rytkönen Päivi Peura Pekka Urtti Arto 《Pharmaceutical research》1991,8(12):1539-1542
0,0-(l,4-Xylylene) bispilocarpic acid esters are pilocarpine pro-drugs containing two pilocarpic acid monoesters linked with one pro-moiety. Each mole of prodrug forms two pilocarpine moles in the presence of esterases. Corneal uptake and permeability of various bispilocarpic acid diesters were investigated in vitro using isolated albino rabbit corneas. The permeability coefficient of pilocarpine was 2.8 × 10 –6 cm/sec, whereas for bispilocarpic acid diesters, despite their large molecular weights (between 638 and 722), permeability coefficients were 6.5–20.2 × 10 –6 cm/sec. Only pilocarpine, and no intact prodrug, was observed at the endothelial side. Corneal uptake was increased with increasing lipophilicity, but a parabolic relationship between the logarithm of the apparent partition coefficient (1-octanol–pH 7.4 phosphate buffer) (log PC) and the corneal permeability was noticed. Corneal permeability and the rate of enzymatic hydrolysis of the compounds correlated well. The corneal permeability of pilocarpine given as lipophilic bispilocarpic acid diester (log PC 3) prodrugs seems to be controlled by the formation of pilocarpine in the corneal epithelium rather than by the absorption of prodrugs into the epithelium or their epithelium–stroma transport rate. 相似文献