Photoactive barbiturate receptors: an ultimate lock-and-key system in which the key unlocks the lock.
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Conditional photofragmentation is achieved with binary systems incorporating the isophthaloyl bis-aminopyridine barbiturate recognition motif and dithiane- or trithiane-based photolabile modules, which cleave only in the presence of an external sensitizer. The components of the host-guest molecular recognition pair were each outfitted with either the sensitizer or the photocleavable module. In these pairs, photoinduced fragmentation is contingent on a molecular recognition event, which brings the sensitizer into the immediate proximity of the photolabile latch. [structure: see text] (+info)
Observation of the development of tolerance to and physical dependence on barbital by cortical evoked potential in rats.
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To observe the dispositional and functional tolerance to and physical dependence on barbital, the influence of repeated administration of the drug on serum barbital levels, coordinative motion, body weight, and cortical evoked potential was assessed. Rats administered the first dose of barbital showed marked impairment of gross behavior and then loss of the righting reflex. While they were repeatedly treated with barbital for a 4-week period, the CNS depression became weaker and weaker, and loss of the righting reflex was no longer observed. Serum barbital levels after administration of barbital tended to decrease by the 28th day of repeated drug administration. Coordinative motion was markedly impaired after administration of the first dose, but gradually recovered during the repeated administration period. Barbital at 100 mg/kg, i.p., prolonged the latent time of the evoked potential in normal untreated rats but not in tolerant rats. During the withdrawal period, no particular change was observed in the animals' gross behavior. However, body weight loss and shortening of the latent time of the evoked potential were observed at 60 to 72 hours of withdrawal. These results suggest that cortical evoked potential can serve as a useful method for observing tolerance to and physical dependence on barbital. (+info)
Oncological outcomes in rats given nephrocarcinogenic exposure to dietary ochratoxin a, followed by the tumour promoter sodium barbital for life: a pilot study.
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The selective carotid arterial vasoconstrictor action of GR43175 in anaesthetized dogs.
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1. GR43175 is a highly selective agonist at 5-HT1-like receptors in the dog saphenous vein. This study describes the haemodynamic effects of GR43175 in barbitone-anaesthetized dogs. 2. GR43175 (1-1000 micrograms kg-1, i.v.) produced dose-dependent decreases in carotid arterial blood flow with little or no change in arterial blood pressure. The decrease in blood flow was associated with an increase in carotid arterial vascular resistance. In preliminary studies, the dose of GR43175 producing 50% of the maximum carotid vasoconstrictor response was 39 +/- 8 micrograms kg-1, i.v. 3. In comparative regional haemodynamic studies, GR43175 (1-1000 micrograms kg-1, i.v.) had little effect on total peripheral resistance or resistance in the mesenteric, vertebral and coronary arterial vascular beds. Low doses of GR43175 decreased, whilst high doses (100 micrograms kg-1, i.v. and above) increased femoral arterial vascular resistance. GR43175 (1-1000 micrograms kg-1, i.v.) had no effect on respiratory inflation pressure. In doses of 100 micrograms kg-1 i.v. and above, GR43175 caused small decreases in heart rate. 4. The carotid arterial vasoconstrictor action of GR43175 was resistant to antagonism by the 5-HT2 receptor, 5-HT3 receptor and alpha-adrenoceptor blocking drugs, ketanserin, MDL72222 and phentolamine respectively, but could be antagonized by the non-selective 5-HT1-like receptor blocking drug methiothepin. Methiothepin had no effect on the carotid vasoconstrictor action of the thromboxane A2 mimetic, U46619. 5. The results demonstrate that GR43175 produces a selective vasoconstriction in the carotid arterial circulation of anaesthetized dogs via activation of 5-HT1-like receptors, which appear similar to those mediating contraction of the dog isolated saphenous vein. (+info)
Hyperglycemia can cause membrane lipid peroxidation and osmotic fragility in human red blood cells.
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The present study has examined the effect of elevated glucose levels on membrane lipid peroxidation and osmotic fragility in human red blood cells (RBC). Defibrinated whole blood or RBC were incubated with varying concentrations of glucose at 37 degrees C for 24 h. RBC incubated with elevated levels of glucose showed a significantly increased membrane lipid peroxidation when compared with control RBC. A significant positive correlation was observed between the extent of glucose-induced membrane lipid peroxidation and the osmotic fragility of treated RBC. Glucose-induced membrane lipid peroxidation and osmotic fragility were blocked when RBC were pretreated with fluoride, an inhibitor of glucose metabolism; with vitamin E, an antioxidant; with para-chloromercurobenzoate and metyrapone, inhibitors of the cytochrome P-450 system; or with dimethylfurane, diphenylamine, and thiourea, scavengers of oxygen radicals. RBC treated with elevated glucose concentrations also showed an increase in NADPH levels. Exogenous addition of NADPH to normal RBC lysate induced membrane lipid peroxidation similar to that observed in the glucose-treated RBC. These data suggest that elevated glucose levels can cause the peroxidation of membrane lipids in human RBC. (+info)
Characterization of an adhesion antigen of Streptococcus sanguis G9B.
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An antigen possessing the attributes of an adhesion has been identified in Streptococcus sanguis G9B. Cell surface components were extracted from G9B and a spontaneously occurring nonadherent mutant of G9B, strain Adh-, with a 2 mM barbital buffer, pH 8.6. The extract of G9B but not of Adh- absorbed more than 80% of the adhesion-inhibitory activity of anti-G9B immunoglobulin G (IgG). Immunoblots revealed 80- and 52-kilodalton (kDa) antigens present in the G9B extract but not in the Adh- extract. Absorption of anti-G9B IgG with Adh- and G9B barbital extracts showed a correlation between the loss of the 80- and 52-kDa antibodies and the loss of adhesion-inhibitory activity. An antibody prepared against the 80-kDa antigen excised from sodium dodecyl sulfate-polyacrylamide gels recognized the 80- and 52-kDa antigens and another antigen of 62 kDa but did not inhibit adhesion. However, an antibody from an electroblot containing the native protein from which the 80-kDa and related antigens were derived (the 80-kDa antigen complex) inhibited adhesion to the same extent as anti-G9B IgG. Periodate oxidation of the G9B barbital extract modified the 80-kDa antigen complex and resulted in the loss of 40% of its absorbing activity. The barbital extract also contained an endogenous enzyme responsible for producing the 62- and 52-kDa antigens from the 80-kDa protein and which, under optimal conditions, degraded the antigen completely, resulting in the loss of antibody-absorbing activity. The 80-kDa antigen complex has a molecular mass of more than 200 kDa in native polyacrylamide gels and a pI of 4.1 to 4.8. These observations suggest that the adhesion antigen in S. sanguis G9B is a large glycoprotein from which an 80-kDa antigen complex is derived. (+info)
Streptococcus sanguis surface antigens and their interactions with saliva.
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Saliva-binding molecules of Streptococcus sanguis and their receptors were investigated. Streptococcal cell surfaces were extracted with a barbital buffer and examined immunochemically. Strains G9B and Blackburn, which adhere specifically to saliva-coated hydroxyapatite via immunologically related adhesins, possess 80-, 62-, and 52-kilodalton (kDa), and 52-, 42-, and 29-kDa polypeptides, respectively, which correlate with adhesion to saliva-coated hydroxyapatite. Nonadherent strains Adh- and M-5 lack these antigens. In an immunoblot overlay, the putative adhesins bound to a 73-kDa receptor present in submandibular saliva but not in parotid saliva. G9B also contains a 160-kDa surface protein which bound to an unidentified receptor in both submandibular and parotid saliva samples. Blackburn barbital-extracted components bound to 78- and 70-kDa receptors in parotid saliva. These bacterial-salivary interactions may be important in the regulation of oral ecology. (+info)
P-450 enzyme induction by 5-ethyl-5-phenylhydantoin and 5,5-diethylhydantoin, analogues of barbiturate tumor promoters phenobarbital and barbital, and promotion of liver and thyroid carcinogenesis initiated by N-nitrosodiethylamine in rats.
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Male F344/NCr rats, 6 wk old, were fed 500 ppm of phenobarbital (PB) or equimolar doses of either 5-ethyl-5-phenylhydantoin (EPH) or 5,5-diethylhydantoin (EEH) in diet for 2 wk and hepatic cytochrome P-450-mediated alkoxyresorufin O-dealkylase and aminopyrine N-demethylase activities were determined. Both PB and EPH greatly increased P-450-mediated enzyme activities in rat liver while EEH was ineffective. To evaluate the hydantoins as tumor promoters, 5-wk-old male F344 rats were given a single i.p. injection of 75 mg N-nitrosodiethylamine/kg body weight. Beginning 2 wk later, they were placed either on normal diet or diet containing 500 ppm of PB or equimolar doses of EPH or EEH for the remaining experimental period. Control groups received an i.p. injection of saline followed by each of the test diets. Animals were sacrificed at either 52 or 78 wk. PB and EPH significantly enhanced the development of hepatocellular foci and hepatocellular adenomas at 52 wk and hepatocellular carcinomas at 78 wk in N-nitrosodiethylamine-initiated rats. Neither the incidence of hepatocellular neoplasms nor the number and size of hepatocellular foci was significantly increased by EEH. At 78 wk, both PB and EPH enhanced the development of thyroid follicular cell neoplasms in N-nitrosodiethylamine-initiated rats while no such enhancement was observed with EEH. Thus, EPH, a long-acting sedative/anticonvulsant, like the structurally similar PB, promoted hepatocellular and thyroid follicular cell carcinogenesis and induced the PB-inducible form(s) of cytochrome P-450 (P-450b) in rats. In contrast, EEH unlike barbital failed to promote hepatocellular and thyroid follicular cell carcinogenesis and also failed to induce PB-inducible form(s) of cytochrome P-450 in rats. (+info)