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31.
A new type of pseudodipeptide isostere exampled by Phe ψ[CH2CH(OH)]Phe was synthesized from phenylalanine. The H]V protease inhibitory activity (IC50) of Noa-His-Pheψ[CH2CH(OH)]Phe-Ile-Amp was 0. 8 pmol·L-1. 相似文献
32.
Leukotriene B4 (LTB4) and the protein kinase C activator, 4-beta-phorbol dibutyrate (PDBu), both induced a pronounced and concentration-dependent stimulation of hydrogen peroxide (H2O2) generation by purified guinea pig peritoneal eosinophils in the concentration range 1 nM-1 microM. The LTB4 response was inhibited competitively by the specific LTB4 receptor antagonist, U-75302, with a KB of 25 nM, while the concentration-response curves for both stimuli were shifted rightwards (3.8-fold and 2.8-fold for LTB4 and PDBu, respectively) by the competitive protein kinase C inhibitor, 1-O-hexadecyl-2-O-methylglycerol at a concentration of 300 microM. LTB4 appears, therefore, to induce respiratory burst in eosinophils via a receptor-mediated mechanism involving protein kinase C. 相似文献
33.
Acute toxicity of two pyrethroids,permethrin, and cypermethrin in neonatal and adult rats 总被引:2,自引:0,他引:2
Franco Cantalamessa 《Archives of toxicology》1993,67(7):510-513
The present study aims specifically at obtaining a comparison of the acute toxicity of cypermethrin (CY), a type I pyrethroid, and permethrin (PERM), a type II pyrethroid, administered orally as a single dose to neonatal and adult rats, and at assessing the importance of pyrethroid biotransformation in CY and PERM toxicity through use of drug metabolism inhibitors. Our experiments show that CY is more toxic than PERM to adult and neonatal rats. The sensitivity of neonatal rats both to CY and to PERM toxicity is higher, the younger the animals. CY is much more toxic than PERM in the neonatal rat, compared with the adult. In rats aged 8, 16, and 21 days, pretreatment with piperonil butoxide (PB), a monooxygenase inhibitor, or with tri-o-tolyl phosphate (TOTP), an esterase inhibitor, does not produce significant variations in the lethal effects of CY and PERM. Instead, in the adult rats, a significant increase in CY (X2=5.97;p<0.05) and PERM (X2=4.37;p<0.05) mortality occurred in rats pretreated with esterase inhibitors, whereas no increase in CY and PERM toxicity was found in adult animals pretreated with monooxygenase inhibitor. It was concluded that the higher level of sensitivity of the neonate rat to pyrethroid toxicity is probably due to incomplete development of the enzymes which catalyze the metabolism of pyrethroids in the liver of young animals. It is suggested that ester hydrolysis is an important pyrethroids detoxification reaction in the adult rat. 相似文献
34.
Tailoring immunosuppressive therapy. 总被引:1,自引:1,他引:0
35.
Summary A single glass micropipette voltage clamp technique with intracellular dialysis was used to study the effects of the trapidil derivatives AR 12–456 and AR 12–463 on Ca channel currents carried by Bat+ in isolated ventricular cells from mice hearts. Inspite of a more potent inhibition of the cAMP phosphodiesterase from heart (Bartel et al. 1985) a reversible Ca channel blocking action of both compounds could be observed. The concentration of half maximal block was calculated to about 50 mol/l for both derivatives tested. Neither a shift in the current-voltage relationships nor a significant change in the potential for half maximal activation was found. The maximal Ba2+ -conductance was reduced. The steady state inactivation was shifted towards more negative potentials by application of 100 mol/l AR 12–463. The decay of the Ba currents was accelerated in the range of the applied test potentials between –20 and +20 mV. It is concluded that the new trapidil derivatives with more potent inhibitory action on cardiac phosphodiesterase than trapidil can block myocardial Ca channels.
Send offprint requests to B. Nilius 相似文献
36.
Angelo Sghirlanzoni Davide Pareyson Claudio Benvenuti Giovanni Cei Vittorio Cosi Mariella Lombardi Mariaflavia Nicora Roberta Ricciardi Ferdinando Cornelio 《Journal of neurology》1992,239(3):165-169
Summary The efficacy of intranasally administered neostigmine was tested in 22 patients with generalized myasthenia gravis (MG). Topical therapy to the highly vascularized oropharynx proved to be quickly effective in 5–15 min both clinically and electrophysiologically. Twenty-eight MG patients were then recruited from different centres and their morning doses of oral pyridostigmine were substituted with intranasal neostigmine over a period of 2 or 3 weeks. Intranasal neostigmine proved to be equally efficacious in this regimen. No side-effect was noted even in 4 patients treated in this way for 1 year. Intranasal administration of anti-acetylcholinesterase may be very beneficial: (1) for patients with irregular absorption of oral doses; (2) early in the morning and every time a fast and temporary effect is needed; (3) in bulbar impairment and emergencies, in which a handy atomizer may be life-saving.Presented in part at the XIV World Congress of Neurology, New Delhi, 22–27 October 1989 相似文献
37.
The effects of vasopressin on membrane potential and tension were studied in isolated segments of basilar arteries from the
University of Iowa colonies of normotensive inbred Kyoto-Wistar rats (WKY) and stroke-prone spontaneously hypertensive rats
(SP-SHR). In the presence of vasopressin (0.01–0.3 IU/ml), basilar arteries from WKY, but not from SP-SHR, developed rhythmic
contractions. These contractions were recorded in 13 of 14 WKY basilar arteries, were unaffected by pretreatment with 6-hydroxydopamine,
and were characterized by 20–100 dyne oscillations in tension, occurring 1–3 cycles/min, and superimposed on the vasopressin-induced
contraction (averaging 60 dynes at 0.01 IU/ml or 160 dynes at 0.3 IU/ml). However, resting membrane potentials were not different
in SP-SHR vs. WKY at 37°C, and both strains showed about the same (11 mV) depolarization by 0.1 IU/ml of vasopressin. The
rhythmic contractions were enhanced by K+-free solution, and abolished in the presence of high K+ solution (30 mM), suggesting that active Na+−K+ transport may be involved in modulating the rhythmic activity. These findings are consistent with the hypothesis that the
vasopressin-induced rhythmic contractions in WKY basilar arteries are at least partly dependent on a reduced activity of electrogenic
Na+−K+ active transport in WKY as compared to SP-SHR.
This research was supported by Grant Nos. HL14388 and HL16328 from the National Institutes of Health. Dr. Rusch is the recipient
of Postdoctoral Fellowship HL06907. 相似文献
38.
J. L. Borke A. Caride A. K. Verma J. T. Penniston R. Kumar 《Pflügers Archiv : European journal of physiology》1990,417(1):120-122
We used a monoclonal antibody (5F10) specific for the human erythrocyte plasma membrane Ca++-pump to demonstrate the presence and distribution of Ca++-pump epitopes in rat intestine. In paraffin embedded tissue sections, antibody 5F10 binds to epitopes in the basolateral membranes of absorptive cells in rat duodenum and portions of jejunum but not ileum. Western blot analysis of intestinal mucosal proteins with antibody 5F10 shows binding of antibody to major bands of Mr 135,000 and Mr 72,000, and to lesser bands of Mr 125,000 and Mr 27,000. This pattern was seen in mucosal homogenates of rat duodenal and jejunal cells and to a lesser extent in ileal cells. The Mr 135,000 band corresponds to the molecular weight of Ca++-pumps in other tissues. The other bands correspond in size to known proteolytic fragments of the Ca++-pump. Slot-blot analysis of nitrocellulose immobilized mucosal homogenates shows binding of 5F10 to be greatest in duodenum and least in ileum. Ca++- transport studies by the everted gut sac technique show a correlation between vitamin D induction of active Ca++-transport and the segmental distribution of Ca++-pump epitopes. 相似文献
39.
Stéphane Genet Raymond T. Kado 《Pflügers Archiv : European journal of physiology》1997,434(5):559-567
The contribution of the Na/K ATPase (pump) current to the polarization of the Purkinje cell has been studied using slices
of the rat cerebellum by blocking the pump with dihydro-ouabain (DHO) while recording the membrane potential with microelectrodes
in the somata. From our recordings, it appeared that blocking the pump depolarized the Purkinje cells more rapidly than might
be expected from shifts in Na+ and K+ concentrations, suggesting the removal of a hyperpolarizing current. Application of DHO, in the presence of tetrodotoxin (TTX),
led to calcium spike firing and plateau-like discharges suggesting activation of voltage-dependent calcium channels in the
dendrites. Adding 2 mM Co2+ to the medium did not prevent the depolarizations. Removing calcium from the bathing medium containing 2 mM Co2+ blocked the spiking activity but DHO application still produced a depolarization. Experiments to measure the current inhibited
by DHO indicated that the Na/K pump supplies a constant current of 240 pA. Substitution of the sodium with choline produced
a hyperpolarization, during which DHO had no effect on the membrane potential. Substitution of the sodium with lithium produced
only a slowly developing depolarization. It is concluded that in the cerebellar Purkinje cell, a continuous sodium ion influx
activates the pumps which produce a current that directly contributes to the membrane polarization. Possible pathways for
this sodium influx are discussed.
Received: 3 April 1997 / Received after revision and accepted: 12 May 1997 相似文献
40.
Miura T Goto M Hosoya N Odawara T Kitamura Y Nakamura T Iwamoto A 《Journal of medical virology》2003,70(4):497-505
Mitochondrial DNA (mtDNA) of peripheral blood mononuclear cells (PBMCs) collected from Human immunodeficiency virus 1 (HIV-1)-infected patients and healthy controls were measured longitudinally using real-time polymerase chain reaction to evaluate the effects of antiretroviral agents on mtDNA synthesis in vivo and to assess the value of monitoring mtDNA in PBMCs to predict adverse events amongst these patients. MtDNA levels in PBMCs were significantly decreased in treatment-naive HIV-1-infected patients compared with healthy people. MtDNA levels were not only significantly correlated with CD4(+) T-cell count, but also inversely correlated with HIV-1 viral load. MtDNA levels in untreated patients and healthy controls were stable during the period of observation. On the other hand, amongst patients treated with regimens containing AZT/3TC or d4T/3TC, mtDNA increased during treatment and recovered to levels comparable to healthy controls. In contrast, mtDNA decreased immediately after the initiation of an AZT/ddC-containing regimen. We did not find a correlation between mtDNA levels and changes in clinical parameters. There was no significant difference in mtDNA levels between patients with and those without lipoatrophy. Furthermore, there was no obvious difference in mtDNA levels amongst those patients exhibiting signs and symptoms of peripheral neuropathy. In conclusion, the decrease in mtDNA levels in PBMCs amongst HIV-1-infected patients and its amelioration by antiretroviral therapy may suggest the influence of direct effects on mitochondria or mtDNA by HIV-1 infection. Further investigations are needed to elucidate the mechanisms contributing to decreased mtDNA and the value of mtDNA measurement in the care of HIV-1-infected individuals. 相似文献