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Biomedical subjects

J Kanski

Publications and source records attributed to J Kanski.

At least 19 recordsLinked to original sources
PubMed2001

Antioxidant activity of the organotellurium compound 3-[4-(N,N-dimethylamino)benzenetellurenyl]propanesulfonic acid against oxidative stress in synaptosomal membrane systems and neuronal cultures.

Antioxidant activities of 3-[4-(N,N-dimethylamino) benzenetellurenyl]propanesulfonic acid sodium salt (NDBT) were evaluated in solution, red blood cells, synaptosomal membranes, and cultured hippocampal neuronal cells after exposure to peroxynitrite (ONOO(-)) and hydroxyl radicals. The organotellurium compound NDBT possesses significant activity towards hydrogen peroxide and/or the hydroxyl radical in solution, demonstrated by inhibition of hydroxylation of terephthalic acid. In addition, the compound displayed great antioxidant abilities as shown by: reduction of ONOO(-)-induced 2,7-dichlorofluorescein (DCF) fluorescence in synaptosomes; complete prevention of lipid peroxidation in synaptosomes caused by OH radicals (TBARS), and significant prevention of protein oxidation caused by ONOO(-) and OH, indexed by the levels of protein carbonyls in synaptosomes and neuronal cells. The presence of the compound abolished neuronal cell death caused by ONOO(-). Further, the compound was effective in preventing the oxidative changes in synaptosomal membrane protein conformation and crosslinking (EPR spin labeling). Finally, the organotellurium molecule attenuated peroxynitrite-induced, luminol-dependent chemiluminescence in red blood cells--an index of cellular oxidation. These findings demonstrate the great potential of the antioxidant and are consistent with the notion that NDBT may have a role to play in modulating oxidative stress in neurodegenerative disorders, including Alzheimer's disease.

Alkanesulfonic Acids↗
PubMed2001

Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins.

Protein oxidation, one of a number of brain biomarkers of oxidative stress, is increased in several age-related neurodegenerative disorders or animal models thereof, including Alzheimer's disease, Huntington's disease, prion disorders, such as Creutzfeld-Jakob disease, and alpha-synuclein disorders, such as Parkinson's disease and frontotemporal dementia. Each of these neurodegenerative disorders is associated with aggregated proteins in brain. However, the relationship among protein oxidation, protein aggregation, and neurodegeneration remain unclear. The current rapid progress in elucidation of mechanisms of protein oxidation in neuronal loss should provide further insight into the importance of free radical oxidative stress in these neurodegenerative disorders.

Aging↗
PubMed2001

Different mechanisms of oxidative stress and neurotoxicity for Alzheimer's A beta(1--42) and A beta(25--35).

Oxidative stress induced by amyloid beta-peptide (A beta) has been implicated in the neurodegeneration observed in Alzheimer's disease (AD) brain. However, the mechanism by which the predominant form of A beta found in AD brains, A beta(1--42), causes oxidative stress and neurotoxicity remains unknown. Numerous laboratories have used the smaller 11-amino acid fragment of the full-length peptide, A beta(25--35), as a convenient alternative in AD investigations since the smaller peptide mimics several of the toxicological and oxidative stress properties of the native full-length peptide. Our observation that the truncated peptide is more rapidly toxic and causes more oxidative damage than the parent A beta(1--42) led us to investigate the cause for this enhanced toxicity of A beta(25--35) in order to gain insight into the mechanism of action of these peptides. These studies reveal that two different mechanisms may be operative in the two peptides; however, the single methionine residue in the peptides appears to play a crucial role in both mechanisms. That methionine is C-terminal in A beta(25--35) seems to be the cause for its exaggerated effects. When the next amino acid in the sequence of A beta(1--42) (valine) is appended to A beta(25--35), the resultant peptide, A beta(25--36), in which methionine is no longer C-terminal, is neither toxic to cultured neurons nor does it cause oxidative damage. Additionally, oxidizing the sulfur of methionine to a sulfoxide abrogates the damaging effects of both A beta(25--35) and A beta(1--42). The putative mechanistic role of methionine in the observed properties of A beta peptides is discussed in the context of the obtained results as is the role of A beta(1--42)-induced oxidative stress in the neurodegeneration found in AD brain.

Alzheimer Disease↗
PubMed2001

5-Aminosalicylic acid protection against oxidative damage to synaptosomal membranes by alkoxyl radicals in vitro.

The antioxidant properties of 5-aminosalicylic acid in vitro were evaluated in a synaptosomal membrane system prepared from gerbil cortical synaptosomes using EPR spin labeling and spectroscopic techniques. MAL-6 (2,2,6,6-tetramethyl-4-maleimidopiperidin-1-oxyl) and 5-NS (5-nitroxide stearate) spin labels were used to assess changes in protein oxidation and membrane lipid fluidity, respectively. Synaptosomal membranes were subjected to oxidative stress by incubation with 1 mM azo-bis(isobutyronitrile) (AIBN) or 1 mM 2,2'-azobis(amidino propane) dihydrochloride (AAPH) at 37 degrees C for 30 minutes. The EPR analyses of the samples showed significant oxidation of synaptosomal proteins and a decrease in membrane fluidity. 5-Aminosalicylic acid also was evaluated by means of FRAP (the ferric reducing ability of plasma) test as a potential antioxidant. 5-Aminosalicylic acid also showed protection against the oxidation in gerbil cortical synaptosomes system caused by AIBN and AAPH. These results are consistent with the notion of antioxidant protection against free radical induced oxidative stress in synaptosomal membrane system by this agent.

Alcohols↗
PubMed1999

The influence of age and extensive intraductal component histology upon breast lumpectomy margin assessment as a predictor of residual tumor.

PURPOSE: Young age and extensive intraductal component (EIC) histology have been shown to be associated with increased local recurrence in women treated with breast conservation therapy. This study was conducted to determine if the status of the lumpectomy specimen margin consistently predicted for residual tumor burden risk irrespective of these variables. METHODS AND MATERIALS: As part of an institutional prospective approach for breast conservation therapy (BCT), 265 cases with AJCC Stage I/II carcinoma with an initial excision margin that was < or =2 mm or indeterminate were subjected to reexcision. The probability of residual tumor (+RE) was evaluated with respect to tumor size, histopathologic subtype (invasive ductal carcinoma, invasive ductal carcinoma with an EIC, and invasive lobular carcinoma), relative closeness of the measured margin, and the extent of margin positivity graded as focal, minimal, moderate, or extensive. The amount of residual tumor was graded as microscopic, small, medium, or large. All variables were analyzed for patient age < or =45 or >45 years. RESULTS: There was no significant difference in the incidence of a +RE according to age < or =45 versus >45 years when the margin was >0 < or =2 mm. Of the patients aged < or =45 years, the incidence of a +RE with a margin that was positive as compared to >0 < or =2 mm was 71% vs. 23%, respectively (p = 0.002). For women >45 years old, the difference in the incidence of +RE comparing margins that were positive or >0 < or =2 mm was not significant at 50% vs. 40%, respectively (p = 0.23). For all cases in aggregate, age < or =45 years was associated with a greater incidence of +RE as compared to patients aged >45 years with the discrepant incidence of a +RE by age strata most pronounced for focally positive margins (60% vs. 18%;p< or =0.05). In a logistic regression analysis, age (per year, as a continuous variable) and an EIC histology were significantly associated with the probability of a +RE (odds ratio [OR] = 0.80, p = 0.05 and OR = 1.9, p = 0.01, respectively). Tumor size was not significant (p = 0.23). In patients with an EIC histology, margin status is generally less predictive for differences in the incidence of a +RE. Further, the overall magnitude of difference in the incidence of a +RE related to age appears to be minimized when an EIC histology is present. In contrast, for cases classified as having non-EIC histology, there is a near-linear relationship for both age strata with respect to margin status and the incidence of a +RE. When histology is classified as non-EIC, age < or =45 years is consistently associated with a greater risk of residual tumor for all margin status categories. When the extent of margin positivity was graded as focal or minimal, residual tumor was semiquantitatively estimated as a medium/large amount in 33% versus 26% of cases aged < or =45 or >45 years, respectively (p = 0.62). CONCLUSION: For positive lumpectomy specimen margins, younger age is associated with an increased residual tumor risk. An EIC histology appears to be associated with an elevated risk of residual tumor irrespective of age and may undermine the predictive utility of margin status. Therefore, age and an EIC histology should be factored into risk assessments for residual tumor that rely upon margin assessment.

Adult↗
PubMed1999

Methionine residue 35 is important in amyloid beta-peptide-associated free radical oxidative stress.

Amyloid beta-peptide (Abeta), the central constituent of senile plaques in Alzheimer's disease (AD) brain, has been shown to be a source of free radical oxidative stress that may lead to neurodegeneration. In the current study Abeta(1-40), found in AD brain, and the amyloid fragment Abeta(25-35) were used in conjunction with electron paramagnetic resonance spin trapping techniques to demonstrate that these peptides mediate free radical production. The methionine residue in these peptides is believed to play an important role in their neurotoxicity. Substitution of methionine by structurally similar norleucine in both Abeta(1-40) and Abeta(25-35), and the substitution of methionine by valine, or the removal of the methionine in Abeta(25-35), abrogates free radical production and protein oxidation of and toxicity to hippocampal neurons. These results are discussed with relevance to the hypothesis that neurodegeneration in Alzheimer's disease may be due in part to Abeta-associated free radical oxidative stress that involves methionine, and to the use of spin trapping methods to infer mechanistic information about Abeta.

Alzheimer Disease↗