Biomedical subjects

Ephrem Engidawork

Publications and source records attributed to Ephrem Engidawork.

8 recordsLinked to original sources

PubMed2006

Toxicological study on Glinus lotoides: a traditionally used taenicidal herb in Ethiopia.

Seeds of Glinus lotoides L. (Molluginaceae) are used traditionally in the treatment of tapeworm infestation in Ethiopia. Previous studies on its anthelmintic activities confirmed its traditional claims, but data on safety profile were lacking. To this effect, single and repeated dose oral toxicities of the methanolic extracts of seeds of Glinus lotoides were conducted in rats. Doses of 0, 1000 and 5000 mg/kg of crude extract of Glinus lotoides were employed in single dose toxicity studies, while doses of 0, 250, 500, and 1000 mg/kg were used in repeated toxicity studies. In the single dose toxicity test, oral administration of 5000 mg/kg of Glinus lotoides produced mortality in two females and one male on day 4. No significant differences in body and organ weights were observed between controls and treated surviving animals. Moreover, both gross and microscopic examinations of organs did not show detectable differences between controls and treated animals of both sexes. In repeated dose toxicity studies, no mortality was observed when varying doses of the extracts were administered per day for a period of 28 days. There were no significant differences in body weight, absolute and relative organ weights between controls and treated animals of both sexes. Hematological analysis showed no differences in most parameters examined. In the biochemistry parameter analysis, no significant change occurred. Pathologically, neither gross abnormalities nor histopathological changes were observed. These finding suggest that none of the organs appeared to be target and the data could provide satisfactory preclinical evidence of safety to launch clinical trial on standardized formulation of plant extracts.

Administration, Oral↗

PubMed2006

Comparative proteomic analysis of nucleic acid-binding proteins in ten human tumor cell lines.

Failure in regulation of genes involved in growth and division of cells may result in pathological conditions, particularly cancer. Regulation is exerted at various levels of the transcriptional and post-transcriptional processes involving mainly nucleic acid-binding proteins. Here, we systematically explored the proteome of ten different cell lines in search for proteins potentially serving as molecular markers and/or targets for monitoring prognostic outcome and clinical therapies. High-throughput analysis, two-dimensional electrophoresis coupled to matrix-assisted laser desorption/ionization mass spectrometry, identified 72 nucleotide-binding proteins and their interacting partners, which were differentially expressed in the cell lines investigated. Out of the 72 identified proteins, 33 of them were specifically expressed in a single cell line (for e.g., replication protein A 32 kDa, transcription intermediary factor 1, heterogeneous ribonucleoproteins). Moreover, tumor-related proteins including breast carcinoma amplified sequence 2, zinc finger proteins, chromobox protein homologs were identified in individual cell lines. The present findings demonstrate that rich protein information can be obtained by means of proteomic analysis for better understanding of oncogenesis and pathogenesis in a global way, which in turn represents the basis for the rational designs of diagnostic and therapeutic methods.

Biomarkers, Tumor↗

PubMed2006

Protein chemical identification and characterization of the human variants of far upstream element binding protein in medulloblastoma DAOY cell line.

The assembly of trans-acting proteins on sequence-specific DNA cis-elements is crucial in the regulation of eukaryotic gene expression. Far upstream element binding proteins (FAB) are proteins that regulate the expression of the c-myc oncogene by binding to the far upstream element of the c-myc gene. The present study unambiguously identified the two human variants of FAB (FAB1, FAB2) in the medulloblastoma DAOY cell line and characterized their structure for the first time by tandem mass spectrometry independent of antibody availability and specificity. The study also tentatively assigned the third variant (FAB3) at the level of mass spectrometry, although tandem mass spectrometric analysis failed to corroborate the result. These findings open up an exciting possibility for discerning the cellular roles of FAB in tumor biology.

Amino Acid Sequence↗

PubMed2003

Aberrant expression of peroxiredoxin subtypes in neurodegenerative disorders.

An increasing body of evidence indicates that oxidative stress and damage play a role in the pathogenesis of a number of diseases associated with neurodegeneration, including Down syndrome (DS), Alzheimer's disease (AD) and Pick's disease (PD). Although oxidative stress is a common element in these diseases, specific clinico-pathological phenotypes have been described for each disorder. Development of these phenotypes might be linked, among others, to differences in antioxidant response. The present study is designed to investigate expression of peroxiredoxins (Prxs), the newly characterized family of highly conserved antioxidant enzymes, and other antioxidant enzymes in frontal cortex and cerebellum of DS, AD and PD patients using the technique of proteomics. Levels of Prx I, Mn superoxide dismutase (SOD2) and glutathione-S-transferase omega1 in DS, AD and PD were not significantly different from that of controls in both brain regions investigated. In contrast, Prx II was significantly increased (P<0.05) in frontal cortex of DS, AD and PD, whereas Prx III was decreased in frontal cortex of DS (P<0.01) and PD (P<0.001). Interestingly, Prx VI displayed a significant increase (P<0.05) only in PD frontal cortex. The present data indicate that differential regulation of antioxidant enzymes exist in DS, AD and PD, suggestive of the diversity as well as distinct functional roles of these proteins. Moreover, while up-regulation of Prx II appears to provide evidence for the existence of compensatory response in increased cell loss, up-regulation of Prx VI may be used to discriminate PD from AD as well as DS.

Aged↗

PubMed2003

Expression of hypothetical proteins in human fetal brain: increased expression of hypothetical protein 28.5kDa in Down syndrome, a clue for its tentative role.

Major advances have been made in annotation of sequences of the human genome, although elucidating the functions of these newly discovered genes remains to be a strong challenge. In an effort to give insight into how triplication of chromosome 21 leads to mental retardation in Down syndrome, we have constructed a two-dimensional protein map from control and Down syndrome fetal brain and identified hypothetical proteins with no known functions. Subsequent quantitative analysis of these proteins revealed no apparent change in expression of hypothetical proteins DKZp564P0562.1 (fragment), 16.6, 21.4, 39.5, and 40kDa as well as putative 55kDa protein between controls and Down syndrome fetuses. By contrast, hypothetical protein 28.5kDa was significantly elevated (P<0.05) in fetal Down syndrome. This finding offers an important clue that a hypothetical protein might be involved in the pathomechanisms of brain abnormality in Down syndrome.

Brain↗

PubMed2003

Molecular changes in fetal Down syndrome brain.

Trisomy of human chromosome 21 is a major cause of mental retardation and other phenotypic abnormalities collectively known as Down syndrome. Down syndrome is associated with developmental failure followed by processes of neurodegeneration that are known to supervene later in life. Despite a widespread interest in Down syndrome, the cause of developmental failure is unclear. The brain of a child with Down syndrome develops differently from that of a normal one, although characteristic morphological differences have not been noted in prenatal life. On the other hand, a review of the existing literature indicates that there are a series of biochemical alterations occurring in fetal Down syndrome brain that could serve as substrate for morphological changes. We propose that these biochemical alterations represent and/or precede morphological changes. This review attempts to dissect these molecular changes and to explain how they may lead to mental retardation.

Apoptosis↗

PubMed2003

Perinatal asphyxia exerts lifelong effects on neuronal responsiveness to stress in specific brain regions in the rat.

BACKGROUND: Perinatal asphyxia (PA) causes irreversible damage to the brain of newborns and can produce neurologic and behavioral changes later in life. To identify neuronal substrates underlying the effects of PA, we investigated whether and how neuronal responsiveness to an established stress challenge is affected. METHODS: We used Fos expression as a marker of neuronal activation and examined the pattern of Fos expression in response to acute swim stress in 24-month-old rats exposed to a 20-minute PA insult. RESULTS: Swim stress produced a similar pattern of Fos expression in control and asphyxiated rats in 34 brain areas. Asphyxiated rats displayed a higher number of stress-induced Fos-positive cells in the nucleus of the solitary tract, parabrachial nucleus, periaqueductal gray, paraventricular hypothalamic nucleus, nucleus accumbens, caudate-putamen, and prelimbic cortex. No differences in the Fos response to stress were observed in other regions, including the locus ceruleus, amygdala, hippocampus, or septum. CONCLUSION: These data provide functional anatomic evidence that PA has lifelong effects on neuronal communication and leads to an abnormal, augmented neuronal responsiveness to stress in specific brain areas, particularly in the main telencephalic target regions of the mesencephalic dopamine projections, as well as in a functionally related set of brain regions associated with autonomic and neuroendocrine regulation.

Animals↗

PubMed2002

The brain in Down syndrome (TRISOMY 21).

Down syndrome (DS) is the most common genetic birth defect associated with mental retardation. The mechanism(s) underlying the neuropathology of DS is not completely understood. Different hypotheses have been advanced to explain this mystery, including the gene dosage effect, the amplified developmental instability, and the molecular misreading concept. Overexpression of genes residing in chromosome 21 has been assumed to be a central point in the neuropathology of DS, although reports disagreeing with this notion have also been published. In addition, an accumulating body of evidence indicates that genes located on other chromosomes are also involved in the process. DS thus appears to be a disease process involving numerous gene products and this interaction and interplay in the final analysis determines the outcome of the disease. In this regard, transcription factors, reactive oxygen species and apoptosis related proteins are viewed as potential candidates that play a significant role in the disease process. Therapeutic modalities that target these factors including antioxidants and caspase inhibitors might have some benefit in alleviating the symptoms of DS.

Apoptosis↗