Biomedical subjects

Mark A Sochaski

Publications and source records attributed to Mark A Sochaski.

3 recordsLinked to original sources

PubMed2006

Fatal bromethalin poisoning.

Bromethalin is a neurotoxin found in some rodenticides. A delusional 21-year-old male presented to a hospital with altered mental status the day after ingesting a bromethalin-based rodenticide. He died 7 days after his self-reported exposure to c. 17 mg bromethalin (equivalent to 0.33 mg bromethalin/kg). His clinicopathologic course was characterized by altered mental status, obtundation, increased cerebrospinal fluid pressure, cerebral edema, death, and diffuse histologic vacuolization of the white matter in the central nervous system seen on microscopic examination at autopsy. The presence of a demethylated form of bromethalin in the patient's liver and brain was confirmed by gas chromatography with mass spectrometry. Clinical signs and lesions observed in this patient are similar to those seen in animals poisoned with bromethalin. This case illustrates the potential for bromethalin ingestion to result in fatal human poisoning.

Adult↗

PubMed2005

Kinetics of genistein and its conjugated metabolites in pregnant Sprague-Dawley rats following single and repeated genistein administration.

Diets high in soy-based products are well known for their estrogenic activity. Genistein, the predominant phytoestrogen present in soy, is known to interact with estrogen receptors (ER) alpha and beta and elicits reproductive effects in developing rodents. In the rat, genistein is metabolized predominantly to glucuronide and sulfate conjugates, neither of which is capable of activating ER. Therefore, it is critical to understand the delivery of free and conjugated genistein across the placenta to the fetus following maternal genistein exposure such that the potential fetal exposure to free genistein can be assessed. Genistein (4 or 40 mg/kg) was administered to pregnant Sprague-Dawley rats by oral gavage daily from gestation day (GD) 5 through 19 or on GD 19 alone. Maternal and GD 19 fetal tissues were collected 0.5, 1, 2, 4, 6, 8, 12, and 24 h following administration of the final dose on GD 19. Concentrations of genistein, genistein glucuronide, and genistein sulfate were quantitated by LC-MS/MS. In maternal plasma, genistein glucuronide was the predominant metabolite. In the fetal plasma, genistein glucuronide and genistein sulfate were the primary metabolites. Genistein levels in maternal and fetal plasma were much lower than its conjugates. The concentration of genistein in placental tissue was higher than either conjugate. Fetal concentrations of unconjugated genistein following administration of 40 mg/kg were above the EC50 for ERbeta activation. Repeated administration of 40 mg/kg genistein resulted in minor changes in genistein kinetics in the pregnant rat compared to single administration of the same dose. These data suggest that conjugated forms of genistein are not transported across the placenta. High placental concentrations of genistein indicate the placenta is a potential target organ for genistein action during gestation.

Administration, Oral↗

PubMed2002

Lipid peroxidation and protein modification in a mouse model of chronic iron overload.

Iron-storage diseases are believed to cause organ damage through generation of reactive oxygen species. Using a murine model of iron overload, we found that hepatic iron stores increased logarithmically during 3 weeks of chronic intraperitoneal administration of iron dextran, while hepatic glutathione peroxidase activity declined linearly by approximately 50% during the same period. Plasma concentrations of aliphatic aldehydes increased by 2- to 3-fold, and plasma malondialdehyde (MDA) by 6-fold. Modification of total liver protein by products of lipid peroxidation, including MDA-lysine, 4-hydroxynonenal-lysine, and N(epsilon)-(carboxymethyl)lysine (CML), increased by approximately 3-fold, while levels of the protein oxidation marker, methionine sulfoxide (MetSO), were unchanged. Skin collagen was resistant to modification until the third week, when 2- to 3-fold increases in both CML and MetSO were observed. Our results document that iron overload increases lipid peroxidation, with concomitant increases in reactive aldehydes in plasma and chemical modification of tissue proteins. CML was a sensitive indicator of hepatocellular oxidative stress, compared to MetSO, while extensive modification of extracellular skin collagen was not observed until the late stages of iron overload and oxidative stress. These observations provide direct evidence for the contribution of reactive oxygen species, lipid peroxidation, and reactive carbonyl intermediates to the pathogenesis of iron-overload diseases.

Aldehydes↗