Am J Gastroenterol 2002 May;97(5):1272-3
[Medline record in process]
Publication Types:
PMID: 12014750, UI: 22008908
Order this document
Gastroenterol Clin Biol 2002 Jan;26(1):103-4
PMID: 11938056, UI: 21935197
MMWR Morb Mortal Wkly Rep 2002 Apr 19;51(15):325-9
An estimated 76 million persons contract foodborne illnesses each year in the United States. CDC's Emerging Infections Program Foodborne Diseases Active Surveillance Network (FoodNet) collects data about 10 foodborne diseases in nine U.S. sites to quantify and monitor foodborne illnesses. This report describes preliminary surveillance data for 2001 and compares them with 1996-2000 data. The data show a decrease in the major bacterial foodborne illnesses, indicating progress toward meeting the national health objectives of reducing the incidence of foodborne diseases by 2010. However, the data do not show a sustained decline in some infections, indicating that increased efforts are needed to reduce further the incidence of foodborne illnesses.
PMID: 11990237, UI: 21985609
MMWR Morb Mortal Wkly Rep 2002 Apr 19;51(15):321-3
Since January 1, 2002, human illness after eating pufferfish caught in waters near Titusville, Florida, has been reported (Figure 1). The illnesses were manifested by neurologic symptoms consistent with exposure to paralytic shellfish toxins. Laboratory analysis in early April confirmed the presence of saxitoxin in uneaten pufferfish. This report presents selected case examples and summarizes all cases reported to the Toxic Exposure Surveillance System of the American Association of Poison Control Centers (TESS).
PMID: 11990235, UI: 21985607
N Engl J Med 2002 May 16;346(20):1591-2
PMID: 12015405, UI: 22010387
Toxicol Sci 2002 Jun;67(2):322-8
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 4301 W. Markham St. (Mailslot 638), Little Rock, Arkansas 72205. Department of Pathology, University of Texas Health Science Center, Houston, Texas.
Acetaminophen (AAP) overdose can cause severe liver injury and liver failure in experimental animals and humans. Recently, several authors proposed that apoptosis might be a major mechanism of cell death after AAP treatment. To address this controversial issue, we evaluated a detailed time course of liver injury after AAP (300 mg/kg) in fasted C3Heb/FeJ mice. Apoptotic hepatocytes were quantified in H&E-stained liver sections using morphologic criteria (cell shrinkage, chromatin condensation and margination, and apoptotic bodies). The number of apoptotic hepatocytes remained at baseline (0.2 +/- 0.1 cells/10 high-power fields [HPF]) up to 2 h after AAP administration. However, between 3 and 24 h, apoptotic cell death increased significantly, e.g., 6.3 +/- 0.8 cells/10 HPF at 6 h. Despite the increase in the number of hepatocytes meeting the morphological criteria of apoptosis, this cell fraction remained well below 1% of all parenchymal cells. No evidence for caspase-3 processing or increase in enzyme activity was detected at any time. These results were compared to the overall percent of necrotic cells in liver sections. Confluent areas of centrilobular necrosis were estimated to involve 40-60% of all hepatocytes between 3 and 24 h after AAP administration. These numbers correlated with the increase in plasma alanine aminotransferase activities, which reached a peak level of 5900 +/- 1350 U/l at 24 h. A similar result was obtained with higher doses of AAP and with the use of fed animals. Thus, oncotic necrosis and not apoptosis is the principal mechanism of liver-cell death after AAP overdose in vivo.
PMID: 12011492, UI: 22008311
Toxicol Sci 2002 Jan;65(1):151-9
Department of Pharmacology and Toxicology, Center for Toxicology, The University of Arizona, P.O. Box 210207, Tucson, Arizona 85721-0207, USA.
A number of reports document that Fischer 344 (F344) rats are more susceptible to chemically induced liver injury than Sprague-Dawley (SD) rats. Cadmium (CdCl2), a hepatotoxicant that does not require bioactivation, was used to better define the biological events that are responsible for the differences in liver injury between F344 and SD rats. CdCl2 (3 mg/kg) produced hepatotoxicity in both rat strains, but the hepatic injury was 18-fold greater in F344 rats as assessed by plasma alanine aminotransferase (ALT) activity. This difference in toxicity was not observed when isolated hepatocytes were incubated with CdCl2 in vitro, indicating that other cell types contribute to Cd-induced hepatotoxicity in vivo. Indeed, the sieve plates of hepatic endothelial cells (EC) in F344 rats were damaged to a greater degree than EC in SD rats. Additionally, Kupffer cell (KC) inhibition reduced hepatotoxicity in both strains, suggesting that this cell type is involved in the progression of CdCl2-induced hepatotoxicity. Moreover, enhanced synthesis of heat shock protein 72 occurred earlier in the SD rat. Maximal levels of hepatic metallothionein (MT), a protein associated with cadmium tolerance, were greater in SD rats. These protective factors may limit CdCl2-induced hepatocellular injury in SD compared with F344 rats by reducing KC activation and the subsequent inflammatory response that allows for the progression of hepatic injury.
PMID: 11752694, UI: 21625472
Toxicol Sci 2002 Jan;65(1):135-50
AstraZeneca, Alderley Park, Macclesfield SK10 4TG, Cheshire, United Kingdom.
Overdose of acetaminophen (APAP) causes severe centrilobular hepatic necrosis in humans and experimental animals. Here, to explore its mechanism, we administered APAP at subtoxic (150 mg/kg ip) and toxic (500 mg/kg ip) doses to overnight fasted mice. Animals were sacrificed at different time points from 15 min to 4 h postinjection. We assessed liver toxicity by plasma ALT activity and by electron microscopy. Using nylon filter arrays and RTQPCR, we performed genomics analysis in liver. We ran proteomics on liver mitochondrial subfractions using the newly developed quantitative fluorescent 2D-DIGE method (Amersham Pharmacia Biotech UK Limited). As soon as 15 min postinjection, centrilobular hepatocyte mitochondria were already slightly enlarged and GSH total content dropped by a third at top dose. GM-CSF mRNA, which is a granulocyte specific gene likely coming from resident Kupffer cells, was also induced to its maximum of 3-fold at both doses. Chaperone proteins Hsp10 and Hsp60 were readily decreased by half in mitochondria at both doses, most likely by leaking into cytoplasm. Although APAP is known as an apoptotic trigger, no apoptosis was observed at any time point. Most of the protein changes in mitochondria were present at 15 min postinjection, thus preceding most of the gene regulations. The decrease of ATP synthase subunits and beta-oxidation pathway proteins indicated a loss of energy production. As the morphology of mitochondria was also affected very early at top dose, we concluded that APAP toxicity was a direct action of its known reactive metabolite NAPQI, rather than a consequence of gene regulation. However, the latter will either worsen the toxicity or lead toward cell recovery depending on the cellular damage level.
PMID: 11752693, UI: 21625471
the above reports in Macintosh PC UNIX Text HTML format documents on this page through Loansome Doc