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81.
Pulak K. Chakraborty Thomas J. Mangner Diane C. Chugani Otto Muzik Harry T. Chugani 《Nuclear medicine and biology》1996,23(8):1005-1008
Alpha-[11C]methyl-l-tryptophan (AMT) has been synthesized by stereoselective methylation with [11C]methyl iodide of the lithium-enolate generated by treating dimethyl 2(S),3a(R),8a(S)-(+)-hexahydro-8(phenylsulfonyl) pyrrolo[2,3-b]indole-1,2-dicarboxylate (2) with lithium diisopropyl amide (LDA) at −55 °C, followed by ring opening using trifluoroacetic acid and alkaline hydrolysis of the protecting groups. The crude product was purified by a simple reverse-phase C-18 Sep-Pak procedure. The purified product was isolated with an average radiochemical yield of 53 ± 12% (decay corrected) in 30–35 min from [11C]methyl iodide. At end of synthesis (EOS), 138 ± 35 mCi (n = 24) of product was collected with a specific activity of ca. 1–1.3 Ci/μmol (EOS) (4–5 Ci/μmol @ EOB) starting from 1.5 Ci (EOB) of [11C]CO2. 相似文献
82.
Summary A series of 96 diarylamidine (and diarylimidazoline) derivatives were evaluated for their inhibitory effects on the growth and DNA synthesis of murine leukemia L1210 cells. The amidino- and imidazolino-substituted aryl moieties of the compounds consisted of phenyl, indole, indene, benzofuran, benzo[b]thiophene or benzimidazole. Several of these compounds were found to inhibit L1210 cell proliferation with an ID50 (50% inhibitory dose) of 1 g/ml or lower. Structure-function analysis revealed that the antitumor cell activity of the diarylamidines depended on the planarity of the molecule, the presence of amidino- (or, preferably, imidazolino-) groups on both aryl moieties, the nature of the bridge connecting the two aryl moieties (preferably no bridge at all, phenoxy or ethene) and, finally, the nature of the aryl moieties (preferably, benzofuran or benzo[b]thiophene). Hence, compound 20 (6-(2-imidazolin-2-yl)-2-[4-(2-imidazolin-2-yl)phenyl] benzo[b]thiophene) emerged as the most potent inhibitor of L1210 cell growth (ID50: 0.21 g/ml). Its inhibitory potency was similar to that of the well-known trypanocidal drug ethidium bromide (compound 98). For all diarylamidine derivatives taken together, some correlation (r = 0.612) was noted between the log ID50 for L1210 cell proliferation and the log ID50 for L1210 cell DNA synthesis (as monitored by [methyl
3H]dThd incorporation). These findings suggest that the inhibitory effects of the diarylamidines on L1210 cell proliferation may at least partially reside in an inhibition of DNA synthesis. Compound 41 (2,2-vinylenedi-1-benzofuran-5-carboxamidine), that exhibited a potent antitumor activity in vitro (ID50: 1.5 g/ml), was further evaluated for its antitumor efficacy in vivo and found to increase the median survival time of L1210 cell-inoculated BDF1 mice up to 204%, if administered at a dose of 200 mg/kg. 相似文献
83.
84.
AnAmblyospora species (microspora, Abblyosporidae) collected in the southeast region of Austria was examined using light and electron microscopic methods. The hosts were larvae ofEusimulium costatum (Diptera, Simuliidae). The merogonial stages were found to be diplocaryotic. During sporogony, eight monocaryotic spores developed in a sporophorous vesicle. The truncate spores measured between 2.9×2.3 and 4.1×3.2 m and had an anisofilar polar tube, the narrow part of which was rather short. Besides tubules and homogeneous, electron-dense inclusions, unique filamentous structures were observed in the episporontal space. The microsporidian was compared with other species showing similar characteristics. Because of the variations observed in its ultrastructure as compared with that of other species, we consider this microsporidian to be a new species and have named itAmblyospora styriaca. 相似文献
85.
Malignant hyperthermia (MH) may occur, when a genetically predisposed individual or pig (MHS) is exposed to triggering agents. The increase in free, ionized sarcoplasmic calcium inducing the vicious circle of MH is believed to result from calcium-induced release with volatile anaesthetics, and from depolarization-induced calcium release with succinylcholine (SCH). The administration of SCH to susceptible humans or pigs frequently produces an increase in masticatory muscle tone. This hitherto ill-defined phenomenon is referred to as "masseter spasm" (MS). We have attempted to elucidate the pathophysiology of MS in a porcine model. METHODS. After the protocol had been approved by the state authorities, 6 MHS pigs were investigated. The pigs were mixed breeds (German Landrace and Dutch Pietrain) and were 9 +/- 1 weeks old with an average body weight of 25.5 kg. Premedication consisted of intramuscular injection of azaperone, 7.5 mg.kg-1. Anaesthesia was induced with piritramide, 1.2 mg.kg-1, administered via a cannulated ear vein. Subsequent to laryngoscopic endotracheal intubation, neuromuscular blockade was achieved with 4 mg pancuronium. Ventilation was set at 12 breaths per minute and adjusted to maintain an end-tidal CO2 concentration of 4.7% by adapting the tidal volume (PhysioFlex). Anaesthesia was maintained with piritramide, 2.25 mg.kg-1.h-1, pancuronium, 0.4 mg.kg-1.h-1, and N2O (60% in O2). Instrumentation included an arterial line, a central venous line, and a fiberoptic pulmonary artery catheter (Oximetrix). Masticatory muscle tone (MMT) was assessed with an intermolar balloon, connected to a pressure transducer and calibrated to zero prior to SCH administration. As a reference variable for effects produced by SCH, intraocular pressure (IOP) was measured manometrically in the anterior chamber. After stabilization of haemodynamic variables, the neuromuscular blockade was allowed to wear off. After recovery of the evoked masseter electromyogram, a paralyzing dose of pancuronium was administered (0.5 mg.kg-1). When paralysis was complete, SCH was administered (1.5 mg.kg-1), followed a few minutes later by dantrolene infusion (5 mg.kg-1 over 10 min). RESULTS. The administration of SCH was followed by clinically unequivocal MH episodes in all pigs, indicated by an increase in oxygen uptake (VO2; PhysioFlex; Fig. 1) and end-tidal CO2 concentration and a decrease in oxygen saturation of mixed venous blood (svO2; Fig. 2). Despite complete neuromuscular blockade (monitored with EMG), SCH produced an increase in MMT in all pigs which was reversed by dantrolene (Fig. 3). The time course of MMT paralleled that of IOP, suggesting a similar underlying mechanism. DISCUSSION. Succinylcholine is a trigger of MH in susceptible individuals; onset of the syndrome may be associated with "masseter spasm". SCH increases extraocular muscle tone, probably by means of stimulating multiply innervated fibers; the resulting IOP increase is not prevented by competitive neuromuscular blockade. The existence of multiple innervated fibers has also been shown in muscle spindles in the deep layers of the masseter, with their stimulation resulting in elevation of the jaw. We speculate that the increases in MMT and IOP observed in this study reflect the same process, i.e. a motor response, initiated by SCH-induced stimulation of the intramyocellular contractile system of multiply innervated muscle fibers, that is independent of neuromuscular transmission. Triggering of MH with SCH despite complete neuromuscular blockage suggests a mechanism other than depolarization-induced calcium increase. And, for the semantics, according to neurological terminology MS should be referred to as contracture not as spasm. 相似文献
86.
Artificial liver 总被引:7,自引:0,他引:7
Without transplantation, approximately 90% of patients with fulminant hepatic failure die. If patients receive a liver transplant, there is often a lag between the need for and the availability of a donor liver. Therefore, there is a definite need for a liver support system to support the patient's own liver function in fulminant hepatic failure and while awaiting transplantation. We have developed an artificial liver system that not only eliminates lipophilic toxins such as phenols, fatty acids, and mercaptans, but also hydrophilic ones such as ammonia. This artificial liver system consists of a monitor, an extracorporeal blood circuit that uses a hydrophilic polysulfone high-flux dialyzer to remove water-soluble metabolites, and a novel hydrophilic liquid membrane filter to remove lipophilic toxins. In more than 100 in vitro experiments using porcine (5 I) blood, the system was evaluated for its ability to remove toxins that are normally increased in hepatic failure. We found that phenol, cresol, and short- and medium-chain fatty acids can be almost completely eliminated from the blood within 5 h. In animal experiments using pigs, we also found no significant changes of blood gases, liver parameters, electrolytes, and blood cell counts. 相似文献
87.
Keitaro Hashimoto Otto Hauswirth Heinz D. Wehner Rolf Ziskoven 《Naunyn-Schmiedeberg's archives of pharmacology》1979,307(1):9-19
Summary The pacemaker current — i
K2 — in cardiac Purkinje fibres was analysed using the voltage clamp technique described by Deck et al. (1964). (–)-Adrenaline (5.5 · 10–6 M) causes the wellknown shift of the Hodkin-Huxley kinetics in the depolarizing direction. Procaine (7.3·10–4 M) does not cause any further shift of s
in the presence of adrenaline. Atenolol (3.8·10–5 M) causes a backshift of the kinetics in the negative direction in the presence of adrenaline and procaine. The instantaneous current-voltage relationship (
) is altered neither with adrenaline, nor with procaine or atenolol. The results exclude the possibility that the local anaesthetic side effect of many beta-adrenoceptor blocking agents may be involved in the backshift of the s-kinetics. The voltage dependence of the reciprocals of the time constants is shifted in a similar way as s
by the sympathomimetic or blocking drugs. Following the application of (–)-adrenaline (5.5·10–6 M) the (–)-isomere of penbutolol (1.7 and 3.5·10–6 M) is about equally effective in shifting the kinetics back as the (+)-isomere (3.5·10–5 M). In the presence of (–)-adrenaline, the (+)- and (–)-forms of penubutolol cause virtually no change of the instantaneous current-voltage relationship,
. Thus, (–)-adrenaline and (+)- and (–)-penbutolol are aiming for the s-kinetics whose voltage dependence is controlled by the electric field near the i
K2-channel of the membrane and do not influence the number of the i
K2-channels. These findings suggest that the sympathomimetic or blocking agents influence the s-kinetics of the pacemaker current i
K2 by altering the electric field; the fully activated current-voltage relationship which is proportional to the number of the open i
K2-channels is not subject to any appreciable modification. The results conclusively show that the kinetics of the pacemaker current can be controlled by beta-adrenoceptors. 相似文献
88.
The ultraviolet absorption spectra of some chlorinated biphenyls 总被引:2,自引:0,他引:2
James D. MacNeil Stephen Safe Otto Hutzinger 《Bulletin of environmental contamination and toxicology》1976,15(1):66-77
The UV spectra of 29 chlorobiphenyls have been examined. With increasing chloro substitution in which there are less than two chlorine groupsortho to the Ph-Ph bond the max values for the band (attributed to conjugation between the two phenyl rings) are shifted to longer wavelengths and for the more highly substituted chlorobiphenyls there is also a bathochromic shift of the main band (due to the benzenoid skeleton). Introduction of two or more chlorine atoms ortho to the Ph-Ph bond results in a hipsochromic shift of band and diminished value due to steric inhibition of resonance between the two phenyl rings. The sterically hindered chlorobiphenyls and the more highly chlorinated Aroclors also exhibit a series of low-intensity finestructured absorption maxima between 268–302 nm. The UV spectra of chlorobiphenyls are particularly diagnostic with respect to the degree of substitution at the 2, 2, 6 and 6 positions and can be used in the structural analysis of separated chlorobiphenyls. The data may also aid in correlating the photochemical reactivities. 相似文献
89.
90.