Summary and recommendations for future research

A novel triblock copolymer of epsilon-caprolactone (CL) and ethylene oxide (E), CL6E90CL6, intended for use in implantable drug-delivery systems, has been subjected to gamma irradiation, in the solid state and in aqueous solution, under different controlled environmental conditions, to assess its stability to a radiation sterilization process. When copolymer matrices were irradiated with doses of irradiation up to 72 kGy in the presence of oxygen, negligible changes were observed in the molar mass, molecular mobility (assessed by pulsed nuclear magnetic resonance spectroscopy) and thermal properties. However, irradiation of matrices in the absence of oxygen (anoxia) induced the formation of cross-links, as indicated by a reduction in the molecular mobility of the copolymer, but without affecting its molar mass and thermal properties. Gamma irradiation of aqueous solutions of CL6E90CL6 in the presence of oxygen induced random polymer chain scission, as evidenced by a reduction in the molar mass, and the formation of a distribution of copolymer chain lengths in solution. Nuclear magnetic resonance relaxation studies showed that irradiation of solutions of CL6E90CL6 at concentrations greater than 4% w/v under anoxic conditions with doses of 54 kGy produced polymer gels with a network structure. These differences in the effects of gamma irradiation on the physicochemical properties of CL6E90CL6 might be germane to the method selected for sterilization of the polymer before its use in implantable drug-delivery systems.     

8-(Sulfostyryl)xanthines: water-soluble A2A-selective adenosine receptor antagonists

8-(Sulfostyryl)xanthine derivatives were synthesized as water-soluble A2A-selective adenosine receptor (AR) antagonists. meta- and para-sulfostyryl-DMPX (3,7-dimethyl-1-propargylxanthine) derivatives 11a and 11b exhibited high affinity to rat A2A-AR in submicromolar concentrations, and were 20- to 30-fold selective versus rat A1-AR. Styryl-DMPX derivatives were inactive at human A2B- and A3-AR. 1,3-Dipropyl-8-p-sulfostyrylxanthine (13) or only a 7-methyl derivative (14) showed similar (13) or higher (14) A2A affinity than 11a and 11b but showed no (13) or only a low degree (14) of selectivity versus A1-, A2B-, and A3-AR. The A2A-selective sulfostyryl-DMPX derivatives exhibit high water-solubility and may be useful research tools for in vivo studies.     

Comparison of glycoprotein components, tryptophan, lipid peroxidation and antioxidants in borderline and severe hypertension and myocardial infarction

Between 1957 and 1993, the Siberian Chemical Complex (Tomsk-7) located in the Tomsk region (Russia) regularly discharged radioactive liquid wastes into the Tom River which resulted in an extensive contamination of large territories with long lived radionuclides such as cesium-137 and strontium-90. In the summers of 1996 and 1997, Research Team of Siberian Medical University conducted biodosimetry and cytogenetic monitoring of pikes (Esox lucius) caught in the Tom River at various distances downstream from the Siberian Chemical Complex (SCC) using the micronucleus test and the gamma spectroscopy. Our findings demonstrated that the difference in frequency of micronucleated erythrocytes between the radiation-exposed fish caught downstream from the SCC and the controls was statistically significant (P < 0.01). Moreover, we found a good correlation between radiocesium concentration and micronucleated erythrocyte frequency in pikes. It was found that both the micronucleated erythrocyte frequency in pike blood and the level of the pike radiocesium concentration depended on the age of pikes. The micronucleated erythrocyte frequency gradually increased from the 1-year-old pikes to the over 20-year-old pikes. On the other hand, the average level of radiocesium concentration gradually increased from the 1-year-old pikes only up to the 10-year-old pikes. There is no correlation between radiocesium concentration and micronucleated erythrocyte frequency in the over 10-year-old pikes.     

Volume of resection in patients treated with breast conservation for ductal carcinoma in situ

The N-terminal domain (1-318 amino acids) of mouse NFkappaB (p65) has been purified to homogeneity from the soluble fraction of Escherichia coli cells expressing this protein. Its complex with a full-length ikappaB-alpha (MAD3, 1-317 amino acids) molecule was generated by binding the E. coli-derived ikappaB-alpha to the purified NFkappaB and purifying the complex by sequential chromatography. The stoichiometry of NFkappaB to ikappaB in the complex was determined to be 2 to 1 by light scattering and SDS-polyacrylamide gel electrophoresis. The secondary structure of the NFkappaB (p65) determined by Fourier-transform infrared (FTIR) spectroscopy is in good agreement with that of the p50 in the crystal structure of the p50/DNA complex, indicating that no significant structural change in NFkappaB occurs upon binding of DNA. The FTIR spectrum of the NFkappaB/ikappaB complex indicates that its secondary structure is composed of 17% alpha-helix, 39% beta-strand, 18% irregular structures, and 26% beta-turns and loops. By comparing these data to the FTIR data for NFkappaB alone, it is concluded that the ikappaB (MAD3) in the complex contains 35% alpha-helix, 27% beta-strand, 22% irregular structures, and 16% beta-turns and loops. Circular dichroism (CD) analysis of a shorter form of ikappaB (pp40) indicates that it contains at least 20% alpha-helix and that the ikappaB subunit accounts for nearly all of the alpha-helix present in the NFkappaB/ikappaB complex, consistent with the FTIR results. The stabilities of NFkappaB, ikappaB, and their complex against heat-induced denaturation were investigated by following changes in CD signal. The results indicate that the thermal stability of ikappaB is enhanced upon the formation of the NFkappaB/ikappaB complex.     

Quinine for leg cramp: time to call a halt?

The MURCS association is traditionally regarded as a disorder limited to the female sex. It has been hypothesized that men displaying the combination of azoospermia, segmentation abnormalities of the cervicothoracic spine and renal anomalies may have a male analogue of MURCS. Here we describe a patient with non-obstructive azoospermia and Klippel-Feil anomaly type II and suggest that this may represent another case of 'MURCS in the male'.     

Osteonecrosis of the femoral head. Hip salvaging with implantation of a vascularized fibular graft

The authors tried to save the hip joint by implanting a vascularized fibular graft, augmented with cancellous bone, into the curetted core of the femoral head that was affected by aseptic necrosis. Forty of 66 hips were observed for a minimum of 20 months and for as long as 66 months (average, 32 months). Clinical assessment according to the cause and severity of the disease was done using the Harris Hip Score. Twenty-eight hips (70%) were rated excellent, 7 (17.5%) were good, 2 (5%) were fair, and 3 (7.5%) failed and were replaced with an artificial joint. Clinically satisfactory results, including good and excellent, were obtained in 35 hips (87.5%). Radiographic evaluation showed improved appearance of the femoral head core in all 15 patients (37.5%) operated on at a precollapse stage of the disease. In 20 hips, the deformity of the femoral head was unchanged (50%), 2 (5%) became worse, and 3 (7.5%) failed. The number of hips with improved appearance as shown on radiographs and those in which the process was unchanged equaled the number of hips with satisfactory clinical results. These data show that the procedure can induce new bone formation that fuses with the affected subchondral bone, thus preventing the articular surface from collapse. This suggests that vascularized fibular grafting is an excellent alternative for hip salvaging when treating femoral head osteonecrosis.