Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic thymidine kinase (TK) and ornithine decarboxylase (ODC) activities were used to quantify the regenerative response to injury with galactosamine. After massive damage with 1000 mg/kg galactosamine, TK activity (DNA synthesis) peaked between 62 and 120 hours. This peak of activity was depressed as much as 91% by six subcoma doses of dimethyl disulfide (DMDS) given between 24 hours and 64 hours after galactosamine administration. Similar doses of octanoic acid (OA) had no effect, and doses of NH4Cl had no effect except at 120 hours. The first peak of ODC activity (initiation of cell growth) at 45 hours was depressed about 60% by six subcoma doses of NH4Cl or DMDS injected between 27 hours and 42 hours. OA again had no effect. After 400 mg/kg galactosamine, a narrow but high peak of TK activity occurred at 62 hours. This peak of activity was depressed more than 50% by six subcoma doses of NH4Cl, OA, or DMDS given between 24 hours and 54 hours. The first peak of ODC activity at 36 hours was similarly reduced by more than 50% by similar doses of each of the toxins given between 24 hours and 34 hours. The overt neurologic effects of the toxins were dissipated within 1 hour of each injection. The depressive effect of NH4Cl and OA on TK and ODC activities during regeneration after massive centrolobular injury with acetaminophen was more consistently present and more extensive than that seen after injury with galactosamine.
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PMID:Effect of hepatic failure toxins on regenerative enzymes in the liver after injury with galactosamine in the rat. 270 58

Hepatic regenerative enzyme (thymidine kinase and ornithine decarboxylase) activities were significantly depressed by subcoma doses of the hepatic failure toxins (NH4+, octanoic acid, and dimethyl disulfide) after selective injury with allyl alcohol. The inhibitory effect of NH4+ was greater than that of dimethyl disulfide, even though the neurologic effects of dimethyl disulfide were approximately comparable with those of the NH4+. There appeared to be a delay in the full expression of the depressive effects of octanoic acid and dimethyl disulfide. The resistance to these two toxins, particularly dimethyl disulfide, may reflect the resistance to injury of the oxidative processes prominent in periportal hepatocyte mitochondria. In comparison with pericentral injury or two-lobe hepatectomy, periportal injury seemed equally susceptible to regenerative enzyme inhibition by NH4+ but less susceptible to the effect of octanoic acid and dimethyl disulfide.
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PMID:Hepatic failure toxins depress liver regenerative enzymes after periportal injury with allyl alcohol in the rat. 337 15

Four injections of subcoma doses of ammonium acetate, octanoic acid or dimethyl disulfide during the first 24 hr after two-lobe hepatectomy in normal rats markedly depressed DNA synthesis as reflected by liver thymidine kinase activity or the incorporation of tritiated thymidine into hepatic DNA. Recovery from the depressant effects of the three toxins took 16 to 28 hr. Similar doses of the same toxins injected hourly for 3 or 5 hr after the two-lobe hepatectomy had similar depressant effects on the early peak of ornithine decarboxylase activity measured at 4 or 6 hr. Recovery occurred within 3 hr perhaps because of the very short half-life of ornithine decarboxylase and its rapid regeneration time. These observations may have implications for the lack of regeneration observed in many patients with fulminant hepatic failure who have accumulated sufficient ammonia, methanethiol and fatty acids over periods of days or weeks to become encephalopathic.
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PMID:Ammonia, octanoate and a mercaptan depress regeneration of normal rat liver after partial hepatectomy. 396 63

After massive liver injury with acetaminophen, subcoma doses of hepatic failure toxins (NH+4, dimethyl disulfide [----methanethiol], octanoic acid) depressed liver thymidine kinase (TK) activity by 78%, 85%, and 90%, respectively, and ornithine decarboxylase (ODC) activity by 40%, 83%, and 78%, respectively. Twenty-four hours after the last dose of the toxins the depressant effects were still evident. The doses of dimethyl disulfide and octanoic acid required for these depressant effects on TK activity were less than half those required for similar effects previously reported after two-lobe hepatectomy of normal rat liver. The dose of NH+4 required was not reduced. None of the toxins depressed ODC activity after the hepatectomy, in contrast to their depressant effects after acetaminophen. Thus doses of the hepatic failure toxins that were about one fourth to one half those needed to induce coma in normal rats inhibited activity of regenerative enzymes after acute massive liver injury with acetaminophen. The effects were persistent for at least 24 hours. These observations may have relevance to the lack of regeneration observed commonly after fulminant hepatic failure in humans.
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PMID:Effect of hepatic failure toxins on liver thymidine kinase activity and ornithine decarboxylase activity after massive necrosis with acetaminophen in the rat. 405 69