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991.
Olech E Freeston JE Conaghan PG Hensor EM Emery P Yocum D 《The Journal of rheumatology》2008,35(4):580-583
OBJECTIVE: To identify the optimal combination for detecting erosions in early rheumatoid arthritis using extremity magnetic resonance imaging (eMRI). METHODS: In 44 patients, eMRI of 1 hand identified 77% who were erosive, 2 hands 89%, and 2 hands and feet 91%. RESULTS: eMRI identified 4 times as many erosions as radiography. At 6 months, eMRI of 1 hand identified an increase in erosions in 50% subjects, 2 hands in 55%, and 2 hands and feet in 55%. When only subjects with a change in erosion score above the smallest detectable difference were considered, these numbers were 30%, 25%, and 20%, respectively. CONCLUSION: eMRI provides superior erosion identification compared to radiography. Imaging 2 hands can be used as a screening tool and 1 hand to monitor erosions over time. 相似文献
992.
Luchowska E Kloc R Wnuk S Olajossy B Wielosz M Urbańska EM 《Pharmacological reports : PR》2008,60(4):574-577
The effect of a beta(2)-adrenergic agonist, clenbuterol on the production of a glutamate receptor antagonist, kynurenic acid was studied in vitro. Clenbuterol enhanced the production of kynurenic acid in brain cortical slices (0.1-1.0 mM) and in glial cultures (1-50 muM). Timolol, a non-selective beta-adrenergic antagonist prevented this effect. The presented data indicate a novel mechanism of action of beta(2)-adrenoceptor agonists and suggest that an increased formation of the endogenous glutamate receptor antagonist, kynurenic acid could partially contribute to their neuroprotective activity. 相似文献
993.
Kaczmarek P Pokoca L Niemirowicz J Majewska E Baj Z 《Pharmacological reports : PR》2008,60(3):399-403
The aim of the study was to test serum concentrations of the chosen cytokines in patients with prostate cancer (PCa) treated with an luteinizing hormone-releasing hormone (LHRH) analogue. We tested interleukin (IL)-2, IL-10, tumor necrosis factor (TNF)-alpha, interferon (INF)-gamma in blood at three time points; I - before the injection, II - 10 days and III - 20 days after the injection in 14 men with PCa. Patients had one depot injection of the LHRH analogue monthly. The cytokine concentrations in serum samples were determined by ELISA method. Prostate specific antigen (PSA) level was examined before and after six months of the LHRH analogue treatment. After six months of the therapy, we observed normalization of serum PSA value from 16.48 ng/ml to 1.45 ng/ml. LHRH analogue injection resulted in a significant drop of the IL-2 concentration, and the value gradually returned to normal in the next 20 days. IL-10 concentration transiently increased and then was down-regulated. Serum TNF-alpha and INF-gamma concentrations in PCa patients were significantly lower compared to controls and were not affected by the treatment. LHRH analogue treatment in PCa patients modulates concentrations of the chosen cytokines which may result both in antitumor and a transient immunosuppressive effect. 相似文献
994.
Bartuś M Łomnicka M Kostogrys RB Kaźmierczak P Watała C Słominska EM Smoleński RT Pisulewski PM Adamus J Gebicki J Chlopicki S 《Pharmacological reports : PR》2008,60(1):127-138
For many years, 1-methylnicotinamide (MNA), a primary metabolite of nicotinamide, has been considered inactive. Recently however, it has been discovered that MNA possesses anti-thrombotic and anti-inflammatory activity. In the present study we investigated whether chronic administration of MNAto hypertriglyceridemic or diabetic rats would reverse endothelial dysfunction characterized by the impairment of nitric oxide (NO)-dependent vasodilatation. Hypertriglyceridemia in rats was induced by fructose-rich (60%) diet, while diabetes was induced by streptozotocin injection (70 mg/kg). After eight weeks, in hypertriglyceridemic or diabetic rats treated or non-treated with MNA(100 mg/kg), we analyzed the magnitude of endothelium-dependent or endothelium-independent vasodilatation in aorta induced by acetylcholine or S-nitroso-N-acetyl-penicilamine (SNAP), respectively, as well as plasma concentration of: cholesterol, triglycerides, glucose, HbA(1c), fructosamine, peptide C, endogenous MNAand its metabolites (M2PY, M4PY). In diabetic rats plasma concentration of glucose, HbA(1c) and fructosamine was elevated (402.08 +/- 19.01 vs. 82.06 +/- 5.41 mg/dl, p < 0.001; 9.55 +/- 0.56 vs. 4.93 +/- 0.24%, p = 0.052 and 2.53 +/- 0.10 vs. 1.14 +/- 0.06 mmol DTF/mg protein, p < 0.001 in diabetic and control rats, respectively). In hypertriglyceridemic rats plasma concentration of triglycerides was elevated (4.25 +/- 0.27 vs. 1.55 +/- 0.12 mmol/l, p < 0.001 in hypertriglyceridemic and control rats, respectively). In both models the NO-dependent vasodilatation in aorta induced by acetylcholine was significantly impaired as compared to control rats, while the response to SNAP was largely preserved. In hypertriglyceridemic rats, 4 weeks of treatment with MNA(100 mg/kg, po) resulted in a three to six-fold increase in endogenous levels of MNA and its metabolites (M2PY and M4PY), the fall in triglycerides concentration in plasma (from 4.25 +/- 0.27 to 2.22 +/- 0.14 mmol/l, p < 0.001), and the preservation of the NO-dependent vasodilatation. In diabetic rats chronic treatment with MNAalso prevented the impairment of NO-dependent vasodilatation, while it displayed only a mild effect on hyperglycemia and did not lower triglycerides concentration. In summary, MNAtreatment decreased plasma triglycerides concentration in hypertriglyceridemic, but not in diabetic rats, while it prevented the development of endothelial dysfunction in aorta in both of these models. Accordingly, the ability of MNAto reverse endothelial dysfunction seems to be independent of its hypolipemic activity. 相似文献
995.
Balboni G Fiorini S Baldisserotto A Trapella C Sasaki Y Ambo A Marczak ED Lazarus LH Salvadori S 《Journal of medicinal chemistry》2008,51(16):5109-5117
Some reference opioids containing the Dmt-Tic pharmacophore, especially the delta agonists H-Dmt-Tic-Gly-NH-Ph (1) and H-Dmt-Tic-NH-(S)CH(CH2-COOH)-Bid (4) (UFP-512) were evaluated for the influence of the substitution of Gly with aspartic acid, its chirality, and the importance of the -NH-Ph and N(1)H-Bid hydrogens in the inductions of delta agonism. The results provide the following conclusions: (i) Asp increases delta selectivity by lowering the mu affinity; (ii) -NH-Ph and N(1)H-Bid nitrogens methylation transforms the delta agonists into delta antagonists; (iii) the substitution of Gly with L-Asp/D-Asp in the delta agonist H-Dmt-Tic-Gly-NH-Ph gave delta antagonists; the same substitution in the delta agonist H-Dmt-Tic-NH-CH2-Bid yielded more selective agonists, H-Dmt-Tic-NH-(S)CH(CH2-COOH)-Bid and H-Dmt-Tic-NH-(R)CH(CH2-COOH)-Bid; (iv) L-Asp seems important only in functional bioactivity, not in receptor affinity; (v) H-Dmt-Tic-NH-(S)CH(CH2-COOH)-Bid(N(1)-Me) (10) evidenced analgesia similar to 4, which was reversed by naltrindole only in the tail flick. 4 and 10 had opposite behaviours in mice; 4 caused agitation, 10 gave sedation and convulsions. 相似文献
996.
Gregoraszczuk EL Milczarek K Wójtowicz AK Berg V Skaare JU Ropstad E 《Reproductive toxicology (Elmsford, N.Y.)》2008,25(1):58-66
This study investigated in vitro endocrine disrupting effects of three mixtures of POPs: 'Marine mix' extracted from Atlantic cod liver, and two mixtures extracted from burbot liver, 'Mj?sa mix' and 'Losna mix'. The POP mixtures were chemically characterized. Co-culture of theca and granulosa cells, were exposed for 48h with different doses of 'Marine mix', 'Mj?sa mix' or 'Losna mix'. As an end point cell viability was determinated by LDH test, steroid analysis by EIA and caspase-3 by colorimetric substrate. Chemical characterization of the mixtures demonstrated that the 'Marine mix' contained high levels of DDTs and PCBs. In the 'Mj?sa mix', the dominant pollutants were BDEs and HBCD. The concentrations of POPs measured in the 'Losna mix' were considerably lower. All mixtures used in the present study had a stimulatory effect on testosterone and estradiol secretion with 'Marine mix'>'Mj?sa mix'>'Losna mix'. These results show that even a mixture containing background concentrations of POPs significantly affected steroid secretion. A higher steroidogenic response in low dose ranges, compared with high dose ranges indicated xenobiotic-conditioning hormesis. This could complicate predictions of effects in risk assessments. 相似文献
997.
Shanbhag A Rabel S Nauka E Casadevall G Shivanand P Eichenbaum G Mansky P 《International journal of pharmaceutics》2008,351(1-2):209-218
An efficient method has been developed for screening solid dispersion formulations that are intended to enhance the dissolution of poorly soluble compounds. The method is based on miniaturization and automation of sample preparation by solvent casting, and dissolution testing, in a 96-well plate format, using less than 0.1mg of compound per well. To illustrate the method, six polymers and eight surfactants were screened, individually and in combination, for their ability to dissolve a compound with aqueous solubility of < 1 microg/ml in simulated intestinal fluid. Screening was performed at an excipient/compound ratio of 10:1, and a polymer/surfactant ratio of 3:1 for ternary formulations. Sixteen of the 48 ternary formulations dissolved the compound to a level > 100 microg/ml, i.e. at least a 100-fold increase over the aqueous solubility. A number of synergies were observed wherein the performance of a ternary formulation greatly exceeded that of either of the corresponding binary formulations. Thirteen 'hits' from screening were scaled up with melt methods, and approximately 2/3 of these showed comparable dissolution enhancement when tested at larger scale. Five of these were administered to rats, and the absolute oral bioavailability ranged from 10 to 23%, versus less than 1% for the unformulated compound. 相似文献
998.
999.
Tahirovic YA Geballe M Gruszecka-Kowalik E Myers SJ Lyuboslavsky P Le P French A Irier H Choi WB Easterling K Yuan H Wilson LJ Kotloski R McNamara JO Dingledine R Liotta DC Traynelis SF Snyder JP 《Journal of medicinal chemistry》2008,51(18):5506-5521
Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors with IC 50 values between 30-100 nM. Potency is strongly controlled by substitution on both rings and the centrally located amine nitrogen. SAR analysis suggests that well-balanced polarity and chain-length factors provide the greatest inhibitory potency. Structural comparisons based on 3D shape analysis and electrostatic complementarity support this conclusion. The antagonists are neuroprotective in both in vitro and in vivo models of ischemic cell death. In addition, some compounds exhibit anticonvulsant properties. Unlike earlier generation NMDA receptor antagonists and some NR2B-selective antagonists, the present series of propanolamines does not cause increased locomotion in rodents. Thus, the NR2B-selective antagonists exhibit a range of therapeutically interesting properties. 相似文献