Biomedical subjects

R Dozeman

Publications and source records attributed to R Dozeman.

5 recordsLinked to original sources

PubMed1989

Effect of hepatic failure toxins on regenerative enzymes in the liver after injury with galactosamine in the rat.

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.

Acetaminophen↗

PubMed1988

Hepatic regenerative enzyme activity after diffuse injury with galactosamine: relationship to histologic alterations.

Massive liver injury with 1000 mg/kg D-galactosamine was followed by a broad peak of thymidine kinase (TK) activity over 62 to 120 hours. The highest mean value was a 29-fold increase in activity. Three peaks of ornithine decarboxylase (ODC) activity were observed over the same time span. The first peak occurred at 45 hours, showing a sevenfold to eightfold increase in activity. Histologic evidence of necrosis peaked at 12 to 24 hours and was prominent over 54 hours. Periportal inflammation in response to the cellular injury was prominent from 12 to 96 hours and peaked at 45 to 62 hours. The curve of mitoses peaked at the same time as that of TK activity but was only 68% as extensive. The first peak of ODC activity occurred before there was any significant presence of mitoses or of TK activity. A smaller dose of 400 mg/kg resulted in a narrow peak of TK activity at 62 hours that was a 37-fold increase in activity. The total TK response was 43% of that seen after the larger dose, about in proportion to the dose given. The first ODC peak, representing the earliest evidence of regeneration, was earlier and more prominent after the 400 mg/kg dose. On the basis of areas under the curves, the amounts of necrosis and of periportal inflammation after 400 mg/kg were 36% of those seen after 1000 mg/kg. Corresponding figures for other response curves were 29% for mitoses, 33% for serum SGPT, and 71% for total ODC activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

PubMed1985

Acetaminophen liver injury: sequential changes in two biochemical indices of regeneration and their relationship to histologic alterations.

Massive liver injury was produced in fasting male Sprague-Dawley rats weighing 200 +/- 25 gm each by gastric administration of 1400 mg/kg acetaminophen. The time sequence of changes in liver ornithine decarboxylase (ODC) activity, which reflects the earliest phases of cell multiplication, liver thymidine kinase (TK) activity, which reflects DNA synthesis, and liver histology (necrosis, mitosis, and repair processes) was recorded. ODC showed the usual biphasic response. By 12 hours, it reached its first peak, a six- to eightfold increase. At this time there was no histologic evidence of necrosis, and serum malate dehydrogenase (MDH), sorbitol dehydrogenase (SDH), and alanine aminotransferase (SGPT) were normal. During the next 12 hours ODC decreased by 60% to 70% and cellular necrosis became evident, and reached a peak at 24 to 36 hours, as did serum MDH, SDH, and SGPT. The serum enzymes fell precipitously at 48 hours, but the histologic evidence of necrosis subsided gradually over 60 hours. The secondary ODC peak, a fourfold increase, coincided with rising activity of TK, which increased 25- to 35-fold over 54 to 72 hours, and then subsided. At 54 hours, when DNA synthesis had already peaked, there was no histologic evidence of repair other than mitoses. However, within the next 6 hours, evidences of repair became prominent, and remained so for another 36 hours before subsiding. Thus, with acetaminophen injury, the initial phases in preparation for cell multiplication occurred before histologic evidence of injury was apparent, and DNA synthesis peaked before other evidence of tissue repair became evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗

PubMed1985

Effect of hepatic failure toxins on liver thymidine kinase activity and ornithine decarboxylase activity after massive necrosis with acetaminophen in the rat.

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.

Acetaminophen↗

PubMed1983

Hyperthyroidism appearing as hyperemesis gravidarum.

Vomiting is a poorly recognized manifestation of hyperthyroidism. During pregnancy, this appearance can be indistinguishable from hyperemesis gravidarum. Two patients with intractable hyperemesis gravidarum were found to have hyperthyroidism. Their symptoms resolved when thyroid functions returned to normal. Given the ease of laboratory confirmation, excellent therapy, and the seriousness of delay in diagnosis, thyrotoxicosis should be considered in patients with unusual or severe hyperemesis gravidarum.

Adult↗