Marginal Folate Deficiency as a Possible Cause of Hyperhomocysteinaemia in Stroke Patients

Peer Reviewe

The Use of N-Terminal Pro-Brain Natriuretic Peptide to Evaluate Vascular Disease in Elderly Patients with Mental Illness

Background: Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) is regarded as a sensitive marker of cardiovascular disease. Vascular disease plays an important role in cognitive impairment. Method: In 447 elderly patients with mental illness, serum NT-proBNP level and the presence or absence of vascular disease according to the medical record were used to categorize patients in different subgroups of vascular disease. Results and Conclusion: Patients with vascular disease and elevated serum NT-proBNP level had a lower cognition level, shorter survival time, lower renal function and a higher percentage of pathological brain imaging than patients with vascular disease and normal NT-proBNP level. Thus, elevated serum NT-proBNP level might be helpful to detect patients who have a more severe cardiovascular disease

Plasma homocysteine, apolipoprotein E status and vascular disease in elderly patients with mental illness

Peer Reviewe

Single domain antibodies: promising experimental and therapeutic tools in infection and immunity

Antibodies are important tools for experimental research and medical applications. Most antibodies are composed of two heavy and two light chains. Both chains contribute to the antigen-binding site which is usually flat or concave. In addition to these conventional antibodies, llamas, other camelids, and sharks also produce antibodies composed only of heavy chains. The antigen-binding site of these unusual heavy chain antibodies (hcAbs) is formed only by a single domain, designated VHH in camelid hcAbs and VNAR in shark hcAbs. VHH and VNAR are easily produced as recombinant proteins, designated single domain antibodies (sdAbs) or nanobodies. The CDR3 region of these sdAbs possesses the extraordinary capacity to form long fingerlike extensions that can extend into cavities on antigens, e.g., the active site crevice of enzymes. Other advantageous features of nanobodies include their small size, high solubility, thermal stability, refolding capacity, and good tissue penetration in vivo. Here we review the results of several recent proof-of-principle studies that open the exciting perspective of using sdAbs for modulating immune functions and for targeting toxins and microbes

Glutathione turnover in human cell lines in the presence of agents with glutathione influencing potential with and without acivicin inhibition of gamma-glutamyltranspeptidase.

Background: We have previously shown that there were great discrepancies between different agents regarding their glutathione stimulating potential and that agents with mainly oxidative effects did not increase concentrations of glutathione in human cell cultures, in contrast to other thiol reactive agents. In order to evaluate whether increased glutathione degradation might be one reason for these discrepancies, we have investigated the effect of different agents with potential influence on glutathione metabolism in human cell cultures with or without acivicin inhibition of gamma-glutamyltranspeptidase (GT), since GT is responsible for the initial degradation of glutathione. Methods: Intra- and extracellular concentrations of glutathione were investigated in HeLa and hepatoma cell cultures, with and without acivicin inhibition of GT, in the presence of oxidative and electrophilic agents (copper ions, hydrogen peroxide and N-ethylmaleimide), hydroquitione, reducing agents (lipoic acid and N-acetylcysteine), and a thiol reactive metal (mercury ions). Results: There were great discrepancies between the different agents regarding their maximal glutathione response (the sum of the intracellular and the extracellular amount of glutathione) in cell cultures. There was only a small increase in total glutathione in the presence of hydrogen peroxide or N-ethylmaleimide before the cell protein decreased compared to findings with mercury ions, lipoic acid or hydroquinone. In both HeLa and hepatoma cell cultures, there were correlations between the original glutathione amount and the total glutathione amount observed after acivicin inhibition. Conclusion: The relatively small increase of glutathione amount in the presence of oxidative and electrophilic agents compared to other thiol reactive agents is not due to increased GT degradation of glutathione

Oxidative stress decreases extracellular homocysteine concentration in human hepatoma (HepG2) cell cultures

Background: Mild hyperhomocysteinemia is associated with premature vascular disease. The mechanism behind the vascular injuries is, however, still unknown. Homocysteine may be catabolized in the trans sulfuration pathway to cysteine. Cystathionine beta-synthase, which catalyses the first step in the transsulfuration pathway is redox-sensitive. We have therefore investigated total extracellular homocysteine turnover in the presence of oxidative stress in human cell lines. Methods: The turnover of total extracellular homocysteine in HeLa and hepatoma cell cultures has been investigated in the presence of hydrogen peroxide. Furthermore, the effect of hydrogen peroxide on the removal of high amounts of exogenously added homocysteine was also studied. Results: Total extracellular homocysteine concentration in hepatoma cell cultures decreased in the presence of hydrogen peroxide, whereas the extracellular homocysteine concentration in HeLa cell cultures was not influenced. There was no significant change of intracellular homocysteine in any type of cell cultures. Furthermore, the presence of hydrogen peroxide did not increase the removal of exogenously added homocysteine. Conclusion: The presence of hydrogen peroxide probably increases the activity of the transsulfuration pathway in hepatoma cell cultures, which increases the intracellular use of homocysteine and lowers its extracellular release. Consequently this mechanism might tend to lower total plasma homocysteine concentration in oxidative stress. (c) 2006 Elsevier Ireland Ltd. All rights reserved