Binding of acetaldehyde to a glutathione metabolite: mass spectrometric characterization of an acetaldehyde-cysteinylglycine conjugate

BACKGROUND: Ethanol administration decreases hepatic glutathione levels and increases urinary sulfhydryl excretion. Ethanol-induced liver injury is blunted by the administration of glutathione precursors. Acetaldehyde generated in the metabolism of ethanol binds to a number of amino acid residues in proteins and peptides, but it does not react readily with glutathione. Due to the possible role of acetaldehyde in cysteine and glutathione homeostasis, we investigated the reaction of acetaldehyde to cysteinylglycine, the dipeptide generated in vivo in the hydrolysis of glutathione by gamma-glutamyltransferase. METHODS: A conjugate between acetaldehyde and cysteinylglycine was generated under physiologically relevant conditions, both in vitro and in vivo. It was separated by a new reverse-phase high-performance liquid chromatography method and identified by electrospray ionization/ion trap tandem mass spectrometric analysis. RESULTS: The conjugate with a stoichiometry of 1:1 between cysteinylglycine and acetaldehyde is most rapidly generated in vitro and was identified by mass spectroscopy as 2-methyl-thiazolidine-4-carbonyl-glycine. This thiazolidine derivative is stable in vitro and in biological fluids of rats. The conjugate was present in high concentrations in the bile of rats pretreated with ethanol and an inhibitor of aldehyde dehydrogenase. CONCLUSIONS: The sequestering of cysteinylglycine by acetaldehyde occurs rapidly under physiologic conditions. Long-lived sulfur-containing biomolecules that incorporate acetaldehyde might affect cysteine and glutathione homeostasis and may also play a protective role by reducing circulating acetaldehyde levels. The acetaldehyde conjugate or its metabolic products could potentially serve as markers of ethanol consumption.     

Radiation-induced leukemia risk among those aged 0-20 at the time of the Chernobyl accident: a case-control study in the Ukraine

A case-control study was conducted to estimate the radiation-induced acute leukemia risk for the period 1987-1997 among residents aged 0-20 at the time of the Chernobyl accident in the most radioactively contaminated territories of the Ukraine (Rivno and Zhytomir regions). Data were collected on 272 leukemia cases diagnosed between 1 January 1987 and 31 December 1997. Of these, 98 cases were verified and interviewed. Verified cases were compared to 151 randomly selected controls matched by age, gender and type of settlement. The mean value of the estimated accumulated equivalent dose to the bone marrow was 4.5 mSv, and the maximum value was 101 mSv. A statistically significant increased risk of leukemia was found among males whose estimated radiation exposure was higher than 10 mSv. This association was statistically significant for acute leukemia cases that occurred in the period 1993-1997, particularly for acute lymphoblastic leukemia. A similar association was found for acute myeloid leukemia, diagnosed in the period 1987-1992.     

Novel tetrahedral cobalt(ii) silanethiolates: structures and magnetism

Three heteroleptic complexes of Co(ii) tri-tert-butoxysilanethiolates have been synthesized with piperidine [Co{SSi(OtBu)₃}₂(ppd)₂] 1, piperazine [Co{SSi(OtBu)₃}₂(NH₃)]₂(μ-ppz)·2CH₃CN 2, and N-ethylimidazole [Co{SSi(OtBu)₃}₂(etim)₂] 3. The complexes have been characterized by a single-crystal X-ray, revealing their tetrahedral geometry on Co(ii) coordinated by two nitrogen and two sulfur atoms. Complexes 1 and 3 are mononuclear, whereas 2 is binuclear. The spectral properties and thermal properties of 1–3 complexes were established by FTIR spectroscopy for solid samples and TGA. The magnetic properties of complexes 1, 2, and 3 have been investigated by static magnetic measurements and X-band EPR spectroscopy. These studies have shown that 1 and 3, regardless of the similarity in structure of CoN₂S₂ cores, demonstrate different types of local magnetic anisotropy. Magnetic investigations of 2 reveal the presence of weak antiferromagnetic intra-molecular Co(ii)–Co(ii) interactions that are strongly influenced by the local magnetic anisotropy of individual Co(ii) ions.

Structural, spectral and thermal properties of three tetrahedral Co(ii) silanethiolates were established by XRD, FTIR for solid samples and TGA. The magnetic properties were investigated by static magnetic measurements and X-band EPR spectroscopy.     

Socially-Integrated Transdisciplinary HIV Prevention

Current ideas about HIV prevention include a mixture of primarily biomedical interventions, socio-mechanical interventions such as sterile syringe and condom distribution, and behavioral interventions. This article presents a framework for socially-integrated transdisciplinary HIV prevention that may improve current prevention efforts. It first describes one socially-integrated transdisciplinary intervention project, the Transmission Reduction Intervention Project. We focus on how social aspects of the intervention integrate its component parts across disciplines and processes at different levels of analysis. We then present socially-integrated perspectives about how to improve combination antiretroviral treatment (cART) processes at the population level in order to solve the problems of the treatment cascade and make “treatment as prevention” more effective. Finally, we discuss some remaining problems and issues in such a social transdisciplinary intervention in the hope that other researchers and public health agents will develop additional socially-integrated interventions for HIV and other diseases.     

Peptide Microarray Analysis of In Silico-Predicted Epitopes for Serological Diagnosis of Toxoplasma gondii Infection in Humans

Toxoplasma gondii infections occur worldwide in humans and animals. In immunocompromised or prenatally infected humans, T. gondii can cause severe clinical symptoms. The identification of specific epitopes on T. gondii antigens is essential for the improvement and standardization of the serological diagnosis of toxoplasmosis. We selected 20 peptides mimicking linear epitopes on GRA1, GRA2, GRA4, and MIC3 antigenic T. gondii proteins in silico using the software ABCpred. A further 18 peptides representing previously published epitopes derived from GRA1, SAG1, NTPase1, and NTPase2 antigens were added to the panel. A peptide microarray assay was established to prove the diagnostic performance of the selected peptides with human serum samples. Seropositive human serum samples (n = 184) were collected from patients presenting with acute toxoplasmosis (n = 21), latent T. gondii infection (n = 53), and inactive ocular toxoplasmosis (n = 10) and from seropositive forest workers (n = 100). To adjust the cutoff values for each peptide, sera from seronegative forest workers (n = 75) and patients (n = 65) were used. Univariate logistic regression suggested the significant diagnostic potential of eight novel and two previously published peptides. A test based on these peptides had an overall diagnostic sensitivity of 69% (100% in ocular toxoplasmosis patients, 86% in acutely infected patients, 81% in latently infected patients, and 57% in seropositive forest workers). The analysis of seronegative sera performed with these peptides revealed a diagnostic specificity of 84%. The results of our study suggest that the use of a bioinformatic approach for epitope prediction in combination with peptide microarray testing is a powerful method for the selection of T. gondii epitopes as candidate antigens for serological diagnosis.     

Missing Ingredients in Shared Decision-Making?

Shared decision-making (SDM) is a collaborative approach to making decisions in health care, and is a cornerstone of person-centered care. While providers are increasingly expected to utilize SDM in routine practice, widespread and sustainable implementation has proven difficult, especially in the care of individuals diagnosed with serious mental illnesses, and physicians and patients continue to identify barriers to effective collaboration. To date, SDM research has largely focused on the provision of high-quality clinical information from doctors to patients to the neglect of what may be the most important, and transformative, aspect of SDM—the relationship itself. In this forum, the lack of attention to the relationship in SDM research and practice will be explored, along with the relational qualities that need to be in place to implement SDM in the care of persons with serious mental illness based on the findings from a mixed-methods, participatory research project.