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Joseph Abraham

Publications and source records attributed to Joseph Abraham.

5 recordsLinked to original sources
PubMed2006

Autoimmune hepatitis triggered by statins.

Although the cause of autoimmune hepatitis (AIH) is unknown, drugs are believed to be potential triggers in some patients. In isolated case reports, statins have been considered such triggers. Here we describe 3 patients in whom it is probable that statins initiated the development of AIH. Two men (aged 47 and 51) and one woman (aged 57) developed AIH after the initiation of statin therapy. They developed positive titers of antinuclear antibodies, antismooth muscle antibodies (1/40 to 1/160), and hypergammaglobulinemia. Features of all 3 patients met the criteria for AIH according to the International Autoimmune Hepatitis Panel. Liver biopsies in all 3 showed varying stages of fibrosis and plasma cell infiltration, compatible with AIH. The woman developed hepatitis due to statins on 2 separate occasions: the first in 1999, due to simvastatin, and the second in 2001 to 2002, due to atorvastatin, which was severe and persisted even after discontinuing medication. Similarly, in the 2 other cases, exposure to statins preceded development of AIH, which persisted despite discontinuing medications. All 3 patients responded well to prednisone and azathioprine or mycophenolate therapy. 3 similar previously reported cases are reviewed. We conclude that the 3 cases reported here and 3 similar previously reported cases, indicate that severe, ongoing AIH on rare occasions can be triggered by statins.

Atorvastatin↗
PubMed2004

The effects of temperature reduction on gene expression and oxidative stress in skeletal muscle from adult zebrafish.

Longevity is inversely proportional to ambient temperature in ectothermic organisms such as fish. However, the mechanism by which reducing temperature over a physiological range increases life span is not known and available data are derived primarily from invertebrates. With a rodent-like longevity and abundant biological resources, the zebrafish is an ideal vertebrate ectothermic model in which to investigate this phenomenon. As an initial approach, the effects of a year-long 10 degrees C reduction in water temperature on global gene expression in tail skeletal muscle from adult zebrafish were determined using an oligonucleotide microarray representing 15,512 genes. Expression levels for approximately 600 genes were up-regulated by 1.7-fold or greater by the reduction in temperature, while a similar number of transcripts were down regulated by more than 1.7-fold. Using gene ontology (GO) classifications for molecular function, two functional groups, "oxygen and reactive oxygen species metabolism" and "response to oxidative stress," were found to be overrepresented among up-regulated genes. Transcripts levels for the genes in these two categories were increased by temperature reduction (TR). However, temperature reduction did not suppress lipid peroxidation potential, protein carbonyl content, or 8-oxoguanine level. Additional studies will be required to further delineate the role of altered gene expression and oxidative stress on the longevity-promoting effects of temperature reduction.

Aging↗
PubMed2002

Genetic differences in hepatic lipid peroxidation potential and iron levels in mice.

Oxidative damage to macromolecules, including lipids, has been hypothesized as a mechanism of aging. One end product of lipid peroxidation, malondialdehyde (MDA), is often quantified as a measure of oxidative damage to lipids. We used a commercial colorimetric assay for MDA (Bioxytech LPO-586, Oxis International, Portland, OR) to measure lipid peroxidation potential in liver tissue from young (2 month) male mice from recombinant inbred (RI) mouse strains from the C57BL/6J (B6)xDBA/2J (D2) series (BXD). The LPO-586 assay (LPO) reliably detected significant differences (P<0.0001) in lipid peroxidation potential between the B6 and D2 parental strains, and yielded a more than two-fold variation across the BXD RI strains. In both B6 and D2 mice, LPO results were greater in old (23 month) mice, with a larger age-related increase in the D2 strain. As the level of iron can influence lipid peroxidation, we also measured hepatic non-heme iron levels in the same strains. Although iron level exhibited a slightly negative overall correlation (r(2)=0.119) with LPO results among the entire group of BXD RI strains, a sub-group with lower LPO values were highly correlated (r(2)=0.704). LPO results were also positively correlated with iron levels from a group of 8 other inbred mouse strains (r(2)=0.563). The BXD RI LPO data were statistically analyzed to nominate quantitaive trait loci (QTL). A single marker, Zfp4, which maps to 55.2 cM on chromosome 8, achieved a significance level of P<0.0006. At least two potentially relevant candidate genes reside close to this chromosomal position. Hepatic lipid peroxidation potential appears to be a strain related trait in mice that is amenable to QTL analysis.

Aging↗