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141.
Wyrembek P Negri R Kaczor P Czyżewska M Appendino G Mozrzymas JW 《Journal of natural products》2012,75(4):610-616
Falcarindiol (1), a C-17 polyacetylenic diol, shows a pleiotropic profile of bioactivity, but the mechanism(s) underlying its actions are largely unknown. Large amounts of 1 co-occur in water hemlock (Oenanthe crocata) along with the convulsant polyacetylenic toxin oenanthotoxin (2), a potent GABA(A) receptor (GABA(A)R) inhibitor. Since these compounds are structurally and biogenetically related, it was considered of interest to evaluate whether 1 could affect GABAergic activity, and for this purpose a model of hippocampal cultured neurons was used. Compound 1 significantly increased the amplitude of miniature inhibitory postsynaptic currents, accelerated their onset, and prolonged the decay kinetics. This compound enhanced also the amplitude of currents elicited by 3 μM GABA and accelerated their fading, reducing, however, currents evoked by a saturating (10 mM) GABA concentration. Moreover, kinetic analysis of responses to 10 mM GABA revealed that 1 upregulated the rate and extent of desensitization and slowed the current onset and deactivation. Taken together, these data show that 1 exerts a potent modulatory action on GABA(A)Rs, possibly by modulating agonist binding and desensitization, overall potentially decreasing the toxicity of co-occurring GABA-inhibiting convulsant toxins. 相似文献
142.
OBJECTIVE: To elucidate the effects of atrioventricular (AV) dyssynchrony on phase I and phase II oxygen uptake (V(O2)) kinetics in chronotropically competent pacemaker patients during exercise of an intensity comparable to activities of daily living. DESIGN: Blinded patients completed sub-ventilatory threshold (VT) work rate (WR) cycle ergometry exercise in random order during asynchronous AV pacing (AV OFF) and synchronous AV pacing. SETTING: Tertiary care hospital in a major city. SUBJECTS: Six chronotropically competent male pacemaker patients (mean [+/- SD] age, 68 +/- 10 years) with high-degree AV block and varying cardiac histories. RESULTS: The phase I and phase II V(O2) amplitude response and gain (deltaV(O2)/WR ratio) were lower (p < 0.05) and the time course of phase II was slower (p < 0.05) during AV OFF; however, the O2 deficit was similar (p > 0.05) across pacing modes. The stroke volume index (SVI) was consistently lower (p < 0.05) during AV OFF pacing and was significantly correlated with the time course of phase II V(O2). A significant compensatory amplitude response in heart rate (HR) was observed in addition to a higher (p < 0.05) deltaHR/V(O2) ratio during AV OFF. Ventilatory responses were consistent with ventilatory-perfusion mismatching and perceived exertion was higher during asynchronous pacing. CONCLUSION: This study demonstrated that the contribution of SVI affects V(O2) kinetics and underscores the importance of the atrial contribution to ventricular filling and, consequently, to metabolic and hemodynamic responses. This study supports the theory of an O2 transport limitation and further implicates SV as a potential limiting factor during sub-VT exercise intensities that are comparable to those encountered in activities of daily living. 相似文献
143.
144.
Tomaszewski M Charchar FJ Crawford L Zukowska-Sczechowska E Grzeszczak W Sattar N Dominiczak AF 《The American journal of cardiology》2004,94(1):125-126
In this investigation, we compared lipid and inflammatory parameters in regular long distance runners with matched sedentary controls. Long distance runners had significantly lower low-density lipoprotein cholesterol and C-reactive protein levels than the control group. This exercise-induced reduction in low-density lipoprotein cholesterol was independent of the decrease in C-reactive protein levels. 相似文献
145.
Decreased levels of myeloperoxidase in induced sputum of patients with COPD after treatment with oral glucocorticoids 总被引:7,自引:0,他引:7
BACKGROUND: Inhaled glucocorticoids may decrease exacerbations in some patients with COPD, and oral glucocorticoids may improve FEV(1) and shorten hospital stay during exacerbations. The mechanism of these improvements is unknown. This study examines the effect of oral glucocorticoids on markers of neutrophilic airway inflammation. METHODS: Eighteen patients with COPD received oral prednisone, 0.5 mg/kg/d for 2 weeks. Clinical status, lung function measurements, and sputum induction were performed before and after treatment with oral prednisone. Levels of the neutrophil chemoattractant (interleukin-8 [IL-8]) and neutrophil activation marker (myeloperoxidase [MPO]) were measured in the supernatant of induced sputum by enzyme-linked immunosorbent assay. RESULTS: Levels of MPO decreased significantly after treatment with prednisone (p = 0.0004): before treatment median, 2.54 microg/mL (range, 1.49 to 12.58 microg/mL); after treatment median, 1.79 microg/mL (range, 1.32 to 3.57 microg/mL). Treatment with prednisone did not influence the levels of IL-8. CONCLUSIONS: The treatment of patients with COPD with oral glucocorticoids decreases the activation of neutrophils, which may be partially responsible for clinical improvement in these patients. 相似文献
146.
CONCLUSION: The qualitative and quantitative compositions of GAGs were comparable in all the polyps examined. OBJECTIVE: Glycosoaminoglycans (GAGs) are an integral component of proteoglycans, which are constituents of connective tissue. The qualitative and quantitative compositions of GAGs occurring in proteoglycans determine their biological role. In this work, individual fractions of GAGs occurring in nasal polyps were isolated and estimated. MATERIAL AND METHODS: Polyps were obtained over a 2-year period from 31 patients (18 males, 13 females; age range 28-70 years) who underwent polypectomy and evaluated using routine histopathology. RESULTS: The amount of hyaluronic acid in nasal polyps was high, the amounts of dermatane sulphate and chondroitine-6-sulphate were slightly lower and the amounts of chondroitine-4-sulphate, heparin, heparan sulphate and keratan sulphate were the lowest. 相似文献
147.
SCH 58261, an A(2A) adenosine receptor antagonist, counteracts parkinsonian-like muscle rigidity in rats 总被引:3,自引:0,他引:3
The aim of the present study was to find out whether blockade of adenosine A(2A) receptors by a selective antagonist, SCH 58261, influenced parkinsonian-like muscle rigidity. Muscle tone was examined using a combined mechano- and electromyographic method which simultaneously measured muscle resistance (MMG) of a rat hindfoot to passive extension and flexion in the ankle joint and electromyographic activity (EMG) of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity produced by reserpine (5 mg/kg + alpha-methyl-p-tyrosine, 250 mg/kg) was antagonized by SCH 58261 (0.1-5 mg/kg). SCH 58261 (5 mg/kg) also reduced reserpine-enhanced tonic and reflex EMG activities in both the gastrocnemius and the tibialis muscles. Moreover, SCH 58261 in doses of 1 and 5 mg/kg abolished muscle resistance induced by haloperidol (0.5 mg/kg). However, only the highest dose of SCH 58261 (5 mg/kg) decreased tonic EMG activity enhanced by haloperidol. Administration of L-DOPA (75 and 100 mg/kg) dose-dependently decreased the muscle resistance as well as tonic EMG activity evoked by haloperidol. Combined administration of SCH 58261 (0.1 mg/kg) and L-DOPA (50 mg/kg) in doses which did not affect the haloperidol-induced muscle rigidity produced a pronounced synergistic effect. The ability of SCH 58261 to diminish the parkinsonian-like muscle rigidity and to potentiate the effect of L-DOPA in this model seems to indicate a therapeutic value of this compound in the treatment of Parkinson's disease. 相似文献
148.
Nowicki M Adamkiewicz G Bryc W Kokot F 《American journal of obstetrics and gynecology》2002,186(3):340-344
OBJECTIVE: The purpose of this study was to examine the influence of luteinizing hormone-releasing hormone analog goserelin on serum leptin and body composition in women with solitary uterine myoma. STUDY DESIGN: Fifteen women who were regularly menstruating and not obese were included. In all subjects, serum concentrations of leptin, insulin, testosterone, progesterone, and estradiol and body mass index and waist-to-hip ratio were measured before and after 4, 8, and 12 weeks of treatment with goserelin (3.6 mg every 4 weeks). Fat mass and lean body mass were measured by dual energy radiographic densitometry at baseline and after 12 weeks of therapy. Data were analyzed by multiple way analysis of variance and both simple and multiple regression. RESULTS: The treatment caused a significant regression of myoma. Body weight, fat, and lean mass were unchanged. No changes in plasma leptin (even after correction for fat mass) were noted during the treatment. Plasma estradiol decreased below castrate levels. Plasma progesterone decreased significantly, and testosterone tended to decline during the study. At baseline a highly significant positive correlation was found between serum leptin and fat mass. In a multiple regression analysis, neither the change in fat mass nor any of the hormonal parameters explained the significant portion of variance of plasma leptin during the treatment. CONCLUSION: Pharmacologic gonadectomy does not influence plasma leptin concentrations in women if body fat mass is unchanged. 相似文献
149.
Ossowska K Pietraszek M Wardas J Dziedzicka-Wasylewska M Nowicka D Wolfarth S 《Polish journal of pharmacology》2002,54(1):1-9
The aim of the present study was to examine the influence of 3-month administration of the typical neuroleptic haloperidol (1 mg/kg/day) and the atypical one clozapine (30 mg/kg/day) on the expression of the NMDA-R1 mRNA in different brain structures using in situ hybridization in rats. A long-term treatment with haloperidol decreased the NMDA-R1 mRNA level in intermediate and caudal parts of the caudate-putamen and in more caudally localized regions of parietal and frontal cortices, but increased it in the CA1 region of the hippocampus. No significant changes in the nucleus accumbens, insular cortex, CA3 and dentate gyrus of the hippocampus were found after haloperidol administration. Clozapine did not influence the NMDA-R1 mRNA expression in the hippocampus, as well as in the intermediate and caudal regions of the caudate-putamen, but significantly increased it in the rostral region of the latter structure, in the nucleus accumbens and insular cortex. The present study suggests that both these neuroleptics influence the expression of the mRNA of the NMDA-R1 subunit in brain structures which are thought to be important for development of psychotic symptoms. 相似文献