EDTA-induced urothelial cell shedding for the treatment of superficial bladder cancer in the mouse

AIM: The aim of this study was to determine the effect of intravesical EDTA instillation on the development of intravesically implanted tumor cells in normal mice. METHODS: The mouse bladder tumor (MBT-2) model was used in female C3H/eb mice to evaluate the amount of normal urothelial cell shedding, and the degree of tumor growth inhibition following intravesical EDTA instillation in comparison with phosphate-buffered saline (PBS) instillation. RESULTS: At 1 h after instillation, the number of urothelial cells aspirated was 500-1000 per PBS-treated mouse and 10,000-20,000 per EDTA-treated mouse (P < 0.00001). The bladder weight, which reflected the effect of the agent on the tumor, was similar in the untreated and PBS-treated mice (105.46 +/- 46 mg and 106.2 +/- 50 mg, respectively). It was significantly lower in the EDTA-treated mice (80.4 +/- 42 mg) (P = 0.0045). CONCLUSIONS: Intravesical administration of EDTA results in significant normal and neoplastic urothelial cell shedding. Intravesical irrigation with EDTA may prevent adherence of the malignant cells to the bladder wall following tumor resection.     

Aza-peptides. III. Experimental structural analysis of aza-alanme and aza-asparagine-containing peptides

To determine the structural perturbations induced by the CαH→Nα exchange in aza-peptides, we have examined by H NMR and IR spectroscopy various derivatives of the aza-analogues of alanine, aspartic acid and asparagine in different organic solvents with increasing polarity. Their general formulas are: R'-AzXaa-NR²R³, R'-Pro-AzXaa-NR²R³ and R-AzXaa-Pro-NR²R³ (where AzXaa denotes the aza-analogue of the amino acid residue Xaa = Ala, Asp, Asn; R = Boc, Z; R², R³= H, Me, iPr). The aza-analogue of an amino acid residue appears to be a strong p-turn-inducing motif, and the AzAsn carboxamide side-chain is capable of interacting, as a proton donor, with the preceding peptide carbonyl group.     

Structural variations in the crystal structures of two homologous DL-Leu and Δ-Leu containing peptides+

The similar conformations and interaction modes of Ac-DL-Leu-Nme₂ and Ac-Δ-Leu-NMe₂ molecules in the solid state allow the comparison of their geometrical parameters. The most evident variations are essentially restricted to the α,β-unsaturated side-chain which adopts the Z-disposition. The dimensions of the peptide backbone are much less sensitive to α,β-unsaturation, with a small shortening by 0.04 Å and 0.02 Å of the N-C^α and C^α-C′ bonds, respectively, and an increase by 6° of the N-C^α- C′ bond angle. The ethylenic and amide groups in the Δ-Leu derivative are far from coplanarity, and a significant electronic conjugation of the π-orbital is likely to be rejected.     

Determination of the ratios of the aromatic amino acid residues by first- or second-derivative UV spectrometry for a simple characterization of peptides

A method for the simultaneous determination of the ratios of the three aromatic amino-acid residues in peptides was set up in acidic conditions. Binary and ternary mixtures of these amino acids were prepared, and first- and second-derivative spectra then calculated from their 0.1 nm resolution spectra between 240 and 320 nm. Certain spectral bands were chosen to differentiate tyrosine from tryptophan on the first-derivative spectra, and phenylalanine from tyrosine and tryptophan on the second-derivative spectra. Variation of the amplitude of the chosen bands was shown to be a linear function of the ratio of the aromatic amino acids in the mixture. This technique was validated with peptides whose sequence was known. The difference between theoretical and experimentally determined ratios was lower than 10%. Since the results are obtained as ratios, neither the concentration nor the nature of the peptide has to be known. The feasibility of application using a photodiode array detector with high resolution in reversed-phase high-performance liquid chromatography is discussed. © Munksgaard 1995.     

Job stress, absenteeism and coronary heart disease European cooperative study (the JACE study): Design of a multicentre prospective study

Background: The motives, objectives and design of a multicentreprospective study on job stress, absenteeism and coronary heartdisease in Europe (the JACE study) is presented in this paper.Some specific gaps in the reviewed literature are explicitlytapped into by the JACE study. Its objectives are i) to comparethe distributions of the Karasek job stress scales for the samebroad categories of occupations in different European countries(in males and females), ii) to study the predictive power ofthe job stress scales and the job strain model for one yearof sickness absence (in males and females) and iii) to studythe predictive power of the job stress scales and the job strainmodel for a three year incidence of coronary heart disease (Inmales only). Methods: In answering these questions, relationsare studied controlling for gender, age, level of education,company size, physical work risks and shift work, as well astraditional risk factors for CHD (i.e serum cholesterol, serumHDL cholesterol, smoking habits and blood pressure). The JACEstudy is a Biomed 1 concerted action. The JACE group consistsof eight participating centres from six countries, i.e. fromBelgium and Sweden (two centres), France, Italy, Spain, Swedenand The Netherlands (each one centre). The coordination of thegroup is in Brussels. The participating centres brought in over15, 000 European workers to test the hypotheses.     

TRIPTOSINE, AN L-5-HYDROXYTRYPTOPHAN DERIVATIVE, REDUCES ALCOHOL CONSUMPTION IN ALCOHOL-PREFERRING RATS

Triptosine is a new L-5-hydroxytryptophan derivative whose effecthas been studied in the Long-Evans alcohol-preferring rat. Atan oral dose of 100 mg/kg once daily, triptosine reduced alcoholconsumption by 42% in the second week of treatment and increasedthat of water by 80%. The results suggest that this precursorof serotonin might play an important role in diminishing preferencefor alcohol and reaccustoming the animal to water, without exertingan anorexic effect.