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.     

Cyclic nucleotides attenuate lipid peroxidation-mediated neuron toxicity

Recent studies suggest that increased lipid peroxidation and lipid peroxidation products, such as 4-hydroxynonenal (HNE), contribute to neuronal loss in conditions associated with oxidative stress. The focus of the present study was to determine possible neuroprotective effects of elevated cyclic nucleotide levels against lipid peroxidation and HNE-mediated neural toxicity. Application of 8-bromo derivative analogs of cAMP or cGMP resulted in attenuation of HNE-induced increases in mitochondrial calcium, reactive oxygen species, and neuron loss. Similar results were obtained when neural cells were pretreated with the phosphodiesterase inhibitors zaprinast or isobutylmethylxanthanine (IBMX). These data are consistent with a possible neuroprotective role for elevated cyclic nucleotide levels in disorders associated with increases in lipid peroxidation and HNE.     

Detection of Candida dubliniensis in oropharyngeal samples from human immunodeficiency virus-infected patients in North America by primary CHROMagar candida screening and susceptibility testing of isolates

Candida dubliniensis has been associated with oropharyngeal candidiasis in patients infected with human immunodeficiency virus (HIV). C. dubliniensis isolates may have been improperly characterized as atypical Candida albicans due to the phenotypic similarity between the two species. Prospective screening of oral rinses from 63 HIV-infected patients detected atypical dark green isolates on CHROMagar Candida compared to typical C. albicans isolates, which are light green. Forty-eight atypical isolates and three control strains were characterized by germ tube formation, differential growth at 37, 42, and 45 degreesC, identification by API 20C, fluorescence, chlamydoconidium production, and fingerprinting by Ca3 probe DNA hybridization patterns. All isolates were germ tube positive. Very poor or no growth occurred at 42 degreesC with 22 of 51 isolates. All 22 poorly growing isolates at 42 degreesC and one isolate with growth at 42 degreesC showed weak hybridization of the Ca3 probe with genomic DNA, consistent with C. dubliniensis identification. No C. dubliniensis isolate but only 18 of 28 C. albicans isolates grew at 45 degreesC. Other phenotypic or morphologic tests were less reliable in differentiating C. dubliniensis from C. albicans. Antifungal susceptibility testing showed fluconazole MICs ranging from 相似文献   

Lack of reactivation of cytomegalovirus (CMV) retinitis after stopping CMV maintenance therapy in AIDS patients with sustained elevations in CD4 T cells in response to highly active antiretroviral therapy

The suppression of human immunodeficiency virus (HIV) replication and elevation in CD4 cells observed with protease inhibitor combination regimens known as HAART (highly active antiretroviral therapy) may allow AIDS patients to undergo an immune recovery that allows them to suppress the progression of cytomegalovirus (CMV) retinitis. Eleven AIDS patients receiving HAART with healed CMV retinitis in whom CMV-specific maintenance therapy was discontinued were studied. Median CD4 cell counts were 42 before the initiation of HAART and 183 at discontinuation of anti-CMV therapy. While a median 1.1 log10 drop in plasma HIV-1 RNA was obtained between starting HAART and withdrawal of maintenance therapy for CMV, only 3 of 11 patients maintained plasma HIV RNA below the limits of detection. Reactivation of CMV retinitis after withdrawal of anti-CMV therapy did not occur in any of the patients observed for a median of 156 days (range, 92-558).     

The future of infertility services

We report on a woman with severe peripheral vascular disease with unstable angina, in which access to the central circulation was not possible from a peripheral route. The translumbar approach was used for coronary angiography and a successful angioplasty of the left circumflex artery.     

Impaired generation of anti-AKR/Gross murine leukemia virus cytotoxic T lymphocytes in mice experimentally infected with MuLV

C57BL/6 (B6) and C57BL/6.Fv-1n (B6.Fv-1n) mice mount AKR/Gross murine leukemia virus (MuLV)-specific cytolytic T lymphocyte (CTL) responses following primary and secondary stimulation with AKR/Gross MuLV-induced tumor cells. In contrast, mice exposed to infectious virus rather than virus-infected cells generate little, if any, antiviral CTL activity. In this report, we show that inoculation of B6 or B6.Fv-1n mice with MuLV prior to priming with H-2-matched AKR/Gross virus antigen-positive tumor cells resulted in a profound inhibition of the virus-specific CTL response. Antiallogeneic major and minor histocompatibility antigen-specific CTL responses were not significantly diminished in MuLV-infected mice. The AKR/Gross MuLV-specific CTL response in B6 mice was inhibited by NB-tropic (SL3-3NB, Friend and Moloney), but not N-tropic (AKR623) MuLV, suggesting that productive infection of host cells was required. We were unable to inhibit the in vitro generation of virus-specific CTL by adding modulator cells from virus-infected mice to mixed lymphocyte-tumor cell cultures (MLTC) of spleen cells from uninfected animals. We also failed to augment CTL generation in MLTC from virus-infected animals by adding exogenous IL-2 or CD4+ lymphocytes from uninfected, tumor-primed mice. Taken together, the data suggested that the inhibition resulted from either a direct or an indirect effect on the in vivo priming of virus-specific CD8+ cells. It is therefore interesting that MuLV such as Friend and Moloney, which do not encode the immunodominant epitope recognized by anti-AKR/Gross MuLV CTL, are nonetheless able to specifically inhibit this response. These results demonstrate a potentially important mechanism by which retroviruses may escape CTL-mediated immunity.