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231.
Biaryls, 7-naphthyl-5-s-amino-2,3-dihydrobenzo[b]thiophene-4-carbonitriles (3a-e), 8-(1-naphthyl)-6-s-amino-isothiochroman-5-carbonitriles (6a-d), 4-(1-naphthyl)-2-s-aminobezocycloalkene-1-carbonitriles (6e-j), 8-naphthyl-6-s-amino-2-ethyl-1,2,3,4-tetrahydro-isoquinoline-5-carbonitrle (6k-n), 1-naphthyl-3-s-amino-10H-9-thia-phenantherene-4-carbonitriles (8a-e) and 1-(1-naphthyl)-3-s-amino-9,10-dihydrophenantherene-4-carbonitriles (8f-i) have been prepared through carbanion induced ring transformation reactions of 6-naphthyl-3-cyano-4-s-amino-2H-pyran-2-ones (1) from respective ketones (2, 5, and 7). These compounds have been evaluated for their glucose-6-phosphatase inhibitory activity and only 6a, c, j, m, c, d, h displayed significant inhibition of the glucose-6-phosphatase. 相似文献
232.
Srivastava S Terjung RL Yang HT 《American journal of physiology. Heart and circulatory physiology》2003,285(3):H1190-H1197
Ischemia-induced angiogenic response is reduced in spontaneously hypertensive rats (SHR). To study whether exogenous basic fibroblast growth factor (bFGF) infusion is effective in expanding collateral circulation in frankly hypertensive SHR, femoral arteries of male SHR (weighing approximately 250 g) were kept intact (nonoccluded control; n = 9) or occluded for 4h(n = 12) or for 16 days with vehicle (n = 14) or bFGF [0.5 (n = 17), 5.0 (n = 13), and 50.0 (n = 14) microg. kg-1. day-1 for 14 days] intraarterially. Maximal collateral-dependent blood flows (BF) to the hindlimbs were determined with 85Sr- and 141Ce-labeled microspheres during running at 20 and 25 m/min (15% grade). Preexercise heart rates (approximately 530 beats/min) and blood pressures (BP; approximately 200 mmHg) were similar across groups except in the high-dose bFGF group, where BP was reduced by approximately 12% (P < 0.05). Femoral artery occlusion for 4 h resulted in approximately 95% reduction of BF in calf muscles [199 +/- 18.7 (nonoccluded group) to 10 +/- 1.0 ml. min-1. 100 g-1; P < 0.001]. BF to calf muscles of the vehicle and low-dose bFGF (0.5 microg. kg-1. day-1) groups increased to 36 +/- 3.2 and 45 +/- 2.0 ml. min-1. 100 g-1, respectively (P < 0.001). bFGF infusion at 5.0 and 50.0 microg. kg-1. day-1 further increased (P < 0.001) BF to calf muscles (62 +/- 4.6 and 62 +/- 2.2 ml. min-1. 100 g-1, respectively). Our results show that bFGF can effectively increase BF in hypertensive rats. The reduced hypertension with high-dose bFGF suggests that a critical signal in arteriogenesis (nitric oxide bioavailability) may be restored. These findings suggest that the dulled endothelial nitric oxide synthase of SHR does not preempt collateral vessel remodeling. 相似文献
233.
Li XM Srivastava K Huleatt JW Bottomly K Burks AW Sampson HA 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(6):3289-3295
Peanut allergy (PNA) is the major cause of fatal and near-fatal anaphylactic reactions to foods. Traditional immunotherapy using peanut (PN) protein is not an option for PNA therapy because of the high incidence of adverse reactions. We investigated the effects of s.c. injections of engineered (modified) recombinant PN proteins and heat-killed Listeria monocytogenes (HKLM) as an adjuvant on anaphylactic reactions in a mouse model of PN allergy. PN-allergic C3H/HeJ mice were treated s.c. with a mixture of the three major PN allergens and HKLM (modified (m)Ara h 1-3 plus HKLM). The effects on anaphylactic reactions following PN challenge and the association with Ab levels and cytokine profiles were determined. Although all mice in the sham-treated groups exhibited anaphylactic symptoms with a median symptom score of 3, only 31% of mice in the mAra h 1-3 plus HKLM group developed mild anaphylaxis, with a low median symptom score of 0.5. Alterations in core body temperature, bronchial constriction, plasma histamine, and PN-specific IgE levels were all significantly reduced. This protective effect was markedly more potent than in the mAra h 1-3 protein alone-treated group. HKLM alone did not have any protective effect. Reduced IL-5 and IL-13, and increased IFN-gamma levels were observed only in splenocytes cultures from mAra h 1-3 plus HKLM-treated mice. These results show that immunotherapy with modified PN proteins and HKLM is effective for treating PN allergy in this model, and may be a potential approach for treating PNA. 相似文献
234.
Théberge JF Mehdi MZ Pandey SK Srivastava AK 《Archives of biochemistry and biophysics》2003,420(1):9-17
Vanadium salts such as vanadyl sulfate (VS), potent inhibitors of protein tyrosine phosphatases, have been shown to mimic, augment, and prolong insulin's action. However, the molecular mechanism of responses to these salts is not clear. In the present studies, we examined if VS-induced effects on insulin action are associated with enhancement or augmentation in the activation state of key components of the insulin signaling pathway. Treatment of insulin receptor-overexpressing cells with insulin or VS resulted in a time-dependent transient increase in phosphorylation and activation of extracellular signal-regulated kinases 1 and 2 (ERK 1/2) that peaked at about 5 min, then declined rapidly to about baseline within 30 min. However, when the cells were treated with VS before stimulation with insulin, sustained ERK 1/2 phosphorylation and activation were observed well beyond 60 min. VS treatment also prolonged the insulin-stimulated activation of phosphatidylinositol 3-kinase (PI3-K), which was associated with sustained interaction between insulin receptor substrate-1 (IRS-1) and the p(85 alpha) subunit of phosphatidylinositol 3-kinase (PI3-K) in response to insulin. These data indicate that prolongation of insulin-stimulated ERK 1/2 and PI3-K activation by VS is due to a more stable complex formation of IRS-1 with the p(85 alpha) subunit which may, in turn, be responsible for its ability to enhance and extend the biological effects of insulin. 相似文献
235.
236.
237.
Dhanasekaran M Srivastava S Raju EB Durani S 《Physiological chemistry and physics and medical NMR》2001,33(2):163-174
Partial 'turn-helix' type modules comprised of LD and DL chiral beta-turns serving as potential helix nucleators have been connected with a view to designing a nascent 'helix-turn-helix' type structure. Conformation of the resultant peptide Boc-(D)Glu-Ala-Aib-Lys-Val-Pro-(D)Asp-Leu-Leu-NHMe has been described in both DMSO and water. 相似文献
238.
Histatin 8 (Lys1-Phe-His-Glu-Lys5-His-His-Ser-His-Arg10-Gly-Tyr12)belongs to a group of related neutral and basic histidine richpeptides present in human salivary secretions that possess fungicidal and bactericidal activities. The conformation of thispeptide has been examined by 1H and 13C 2D-NMR in DMSO-d6, water (pH 4.0) and 40% HFA solutions. MD simulations incorporating NMR data was used to generate the solution conformations. The structures were refined by MARDIGRAS employing the RANDMARDI approach. In both DMSO-d6 and water, the peptide is seen to adopt a -pleated sheet, while HFA induces an -helix structure. The role of these structures in its mechanism of action has been explained. 相似文献
239.
The mechanism of copper resistance in a multiple-metal-resistant natural isolate Pseudomonas putida strain S4 is based on inducible efflux. Active extrusion of copper ions occurs from the cytoplasm during the exponential phase of growth. Involvement of ATPase in the efflux of copper ions has been demonstrated by employing specific inhibitors. The effluxed copper is not thrown out of the cell, but remains in a bound form (to a protein) in the periplasm. Thus, a balance between the intracellular level, to fulfill the metabolic requirements, and the periplasmic sequestration, to evade toxicity, is maintained by this isolate. 相似文献
240.
Effect of ovariectomy and estrogen supplementation on brain acetylcholinesterase activity and passive-avoidance learning in rats 总被引:2,自引:0,他引:2
Das A Dikshit M Srivastava SR Srivastava UK Nath C 《Canadian journal of physiology and pharmacology》2002,80(9):907-914
The effect of ovariectomy and estrogen treatment on the brain acetylcholinesterase activity and cognition in rats was investigated in this study. Ovariectomized and nonovariectomized rats were treated subcutaneously with estradiol dipropionate for 8 d. In the single-trial, passive-avoidance test all the groups showed significant learning and retention of memory as evident by the increase in transfer latency time in trial 2 as compared with trial 1. No-transfer response was significantly increased in the estradiol-dipropionate-treated ovariectomized (80%) and nonovariectomized (60%) group as compared with the ovariectomized (30%) group. Specific activity of acetylcholinesterase was assayed spectrophotometrically in salt-soluble and detergent-soluble fractions of various brain areas: frontal cortex, cerebral cortex, striatum, hippocampus and hypothalamus, thalamus, pons, medulla, and cerebellum. The effect of ovariectomy and estradiol dipropionate was varied in both fractions of these brain areas. Estradiol dipropionate treatment could restore the acetylcholinesterase activity to the control level only in the detergent-soluble fraction of hypothalamus and salt-soluble fraction of hypothalamus, thalamus, and medulla in ovariectomized rats. The results indicate that ovariectomy alters acetylcholinesterase activity in the brain areas but not in a uniform manner and affects only qualitative aspects of cognitive function, which could be improved by estrogen supplementation. 相似文献