The association constant between guanine and a series of cytosine derivatives in dichloromethane was determined by fluorescence quenching experiment of pyrene connected to guanine with methylene ...spacer. The association constant for guanine with 5-methylcytosine is found to be higher than that with cytosine. This enables us to distinguish target cytosine from its derivatives.
The purpose of this study is to estimate the role of permeability-glycoprotein (P-gp) in the technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (99Tc(m)-MIBI) scintigraphy.
71 patients with ...squamous cell carcinoma (39 patients with well differentiated, 19 with moderately differentiated and 13 with poorly differentiated tumour) were examined. Eighteen of these patients underwent 99Tc(m)-MIBI scintigraphy (early and delayed scans). The tumour retention index, obtained from the ratio of the accumulation of the delayed scan to that of the early scan, was divided into three groups. The immunohistochemical evaluation of P-gp expression was performed in all 71 patients. Levels of the P-gp expression were classified into three grades (score 0, 1 and 2). Correlations among the tumour retention index, the P-gp expression and the tumour tissue differentiation were evaluated.
17 of 18 patients showed a decreasing of the tumour retention index ranging from 0.70 to 0.93 (mean+/-SD=0.850+/-0.071). The tumour retention index showed a statistical correlation with the P-gp expression and the tumour tissue differentiation (chi-squared=7.802>7.779, P=0.10 and 16.835>14.860, P=0.005, respectively). Moreover, there was a statistical correlation between the P-gp expression and the tumour tissue differentiation (chi-squared=14.863>14.860, P=0.005).
There is a possibility that the P-gp expression is high in the high-grade malignant tumours and P-gp causes the decrease of tumour retention index.
The photochemistry of p-halogenated anilines (H2NC6H4X-p (XA)) such as p-chloroaniline (CA; X=Cl), p-bromoaniline (BA; X=Br), and p-iodoaniline (IA; X=I) in benzene has been studied by the ...time-variation of microwave dielectric absorption (MWDA) method with respect to the transient behavior of the excited states and intermediates with independent dipole moments. The formation and the transient behavior of CA in the triplet excited state (3CA∗) having the ion pair character of p-aminophenyl cation/Cl−, an ion pair of p-aminophenyl cation/Br−, and a p-aminophenyl radical were observed in benzene from the time profiles of the MWDA signals immediately after the laser flash during 308-nm laser irradiation of CA, BA, and IA. The yields of the cleavage of the CX bond were in the order of CA<BA<IA which reflects the order of the bond dissociation energy (BDE), CA>BA>IA. Decay of 3CA∗ having the character of p-aminophenyl cation/Cl− was observed with a lifetime of 3.8μs. The homolytic cleavage of the CBr bond in 3BA∗ occurs to give a radical pair p-aminophenyl radical/Br which sequentially gives an ion pair p-aminophenyl cation/Br− through electron transfer between radicals. The dissociation of the p-aminophenyl cation/Br− to the p-aminophenyl cation and Br− was observed to occur on a 20μs time scale. On the other hand, homolytic cleavage of the CI bond in 3IA∗ occurs efficiently to give the p-aminophenyl radical and I. Bimolecular reactions of 3CA∗ having the character of the p-aminophenyl cation/Cl− with oxygen and a p-aminophenyl radical with oxygen were found to occur at rate constants of 8.3×107 and 108–109M−1s−1, respectively.
Proinflammatory potency of the nonpeptide bradykinin (BK) B2 receptor agonist FR190997 ...(8‐2,6‐dichloro‐3‐N‐(E)‐4‐(N‐methylcarbamoyl)cinnamidoacetyl‐N‐methylaminobenzyloxy‐2‐methyl‐4‐(2‐pyridylmethoxy)quinoline) was investigated.
Intradermal injection of FR190997 (0.03–3 nmol site−1) into dorsal skin of rats increased vascular permeability in a dose‐dependent manner. The effect was less than that of BK, but it was long‐acting and was inhibited by treatment with FR173657 (3 mg kg−1, p.o.). Captopril (10 mg kg−1, i.p.) did not enhance the plasma extravasation by FR190997 (0.3 nmol site−1) in the presence of soybean trypsin inhibitor (SBTI, 30 μg site−1).
Subcutaneous injection of FR190997 (3 nmol site−1) into the hindpaw of mice markedly induced paw swelling. The oedema lasted up to 3 h after the injection. Administration of indomethacin or NS‐398 (10 mg kg−1, i.p.) significantly reduced it at 3 h after the injection.
Simultaneous i.p. injection of prostaglandin (PG) E2 (1 nmol site−1) or beraprost sodium (0.5 nmol site−1) with FR190997 (5 nmol site−1) greatly enhanced frequency of writhing reactions in mice.
FR190997 (0.3–30 nmol kg−1, i.v.) showed less increase in airway opening pressure (Pao) in the guinea‐pig after i.v. injection. Furthermore, FR190997 (0.03–30 nmol) resulted in a very weak contraction of tracheal ring strips and lung parenchymal sections in vitro.
In mice sponge implants, topical application of FR190997 increased angiogenesis and granulation with enhanced expressions of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) mRNAs.
These results indicate that FR190997 has proinflammatory long‐lasting characteristics and it might be ‘a stable tool’ for studying the role of BK B2 receptor in vivo.
British Journal of Pharmacology (2001) 133, 1296–1306; doi:10.1038/sj.bjp.0704208
Aims
To explore induction of intestinal peptide transporter (PEPT) by protein and amino acid load in human.
Methods
Six healthy subjects had normal (NP, 1.1±0.1g/kg/day) and high (HP, ...2.1±0.2g/kg/day) protein diets, a permissible upper limit intake, and L‐phenylalanine (Phe, 7.5 g/day) for 12 days in a randomized 3‐way crossover study. A single dose of cefdinir (100 mg), a substrate for PEPT, was given on the 13th day. Serial plasma samples were collected and measured by HPLC.
Results
Urinary urea nitrogen levels were increased by HP (5.9±0.5 g/12h (Mean±SD) vs 4.1±0.3 g/12h:NP, p<0.01). Plasma trough Phe levels were increased to 121±13.5% of the basal levels by Phe (p<0.01). However, Cmax, Tmax, AUClast in the HP (802.0±264.3 ng/mL, 3.5±0.5 h, 3347.9±1366.6 ng h/mL) and Phe (878.7±276.0 ng/mL, 3.3±0.8 h, 3549.9±1358.2 ng h/mL) groups were not different from the NP group (839.2±368.2 ng/mL, 3.5±0.8 h, 3628.2±1668.9 ng h/mL).
Conclusions
Intestinal PEPT did not seem to be affected by high protein diet and Phe load within the subjects, duration and doses examined. A further study is planned to confirm induction of PEPT in human.
Clinical Pharmacology & Therapeutics (2005) 77, P81–P81; doi: 10.1016/j.clpt.2004.12.203
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