Search PubMed⌕ Search

Biomedical subjects

H V Tuczek

Publications and source records attributed to H V Tuczek.

At least 37 records · Page 2Linked to original sources

Renal function was not impaired by treatment with 5-aminosalicylic acid in rats and man.

In rat experiments and a clinical trial we have examined the suspected nephrotoxic potential of 5-aminosalicylic acid (5-ASA), the biological active metabolite of sulfasalazine (SZ). Male Wistar rats were treated orally for 4 weeks daily with 30 and 200 mg 5-ASA/kg and 75 and 500 mg SZ/kg. The two renal marker enzymes N-acetyl-beta-D-glucosaminidase (NAG; EC 3.2.1.30), alanineaminopeptidase (AAP; EC 3.4.11.2) and creatinine were monitored in urine. At the end of the experiment rats were sacrificed, the removed kidneys histologically examined and drugs, their metabolites and creatinine measured in plasma and urine. In 9 patients treated chronically for their Crohn's disease with 3 X 0.5 g 5-ASA daily in form of suppositories and an oral preparation urinary excretions of NAG, AAP and serum creatinine were also monitored before and during therapy. Neither the animal experiments nor the observations in patients gave any evidence of nephrotoxic lesions induced by 5-ASA. Thus, our data show that in the doses applied, 5-ASA was devoid of altering renal excretion in rats and man.

Aminosalicylic Acids↗

Investigations concerning the correlation between liver cell proliferation, production of alpha-fetoprotein, and DNA-synthesis of lymphocytes in the spleen of NMRI-mice. An autoradiographic and immunohistochemical study.

To obtain more information concerning the correlation between liver cell proliferation, production of alpha-Fetoprotein (AFP) and DNA-synthesis of lymphocytes in the central and peripheral parts of periarteriolar lymphatic sheaths ( PALS ) of the spleen, these parameters were monitored in intervals of 12h after CCl4-poisoning of NMRI-mice using autoradiographic and immunohistochemical methods. The results indicate that synthesis of AFP is not linked closely to proliferation of hepatocytes because in contrast to DNA-synthesis the production of AFP was only detectable in a very small subpopulation of liver parenchymal cells reaching a peak before the majority of hepatocytes was found to enter the S-phase of the cell cycle. Beyond this, in vivo no general suppressive effect of AFP on proliferation of lymphocytes in preferably T-dependent areas of the spleen could be detected since the 3H-TdR-labeling index in these compartments increased, reaching a peak 48h after the maximum of hepatocytes producing AFP had occurred.

Animals↗

Synthesis of alpha-fetoprotein (AFP) and cell proliferation in regenerating livers of NMRI mice after partial hepatectomy. An immunohistochemical and autoradiographic study with 3H-thymidine.

To get more information concerning the relation between cell proliferation and the synthesis of alpha-fetoprotein (AFP), liver regeneration and AFP production was followed simultaneously in short intervals in NMRI mice after two-thirds hepatectomy using autoradiographic and immunohistochemical methods. The results indicate that AFP synthesis is not linked closely to cell proliferation in the sense that each proliferating hepatocyte synthesizes AFP during a definite phase of the cell cycle. However, AFP production, as measured by the index of anti-AFP positive hepatocytes, occurs in a very small population of parenchymal cells when the bulk of the hepatocytes has just passed the S-phase and is considered to be in the G2-, M or early G1-phase of the cell cycle when the cells are still in an undifferentiate state.

Animals↗

Synchronization of hepatocellular DNA synthesis in regenerating rat liver by continuous infusion of hydroxyurea.

Hydroxyurea (HU) inhibited DNA synthesis in the livers of partially hepatectomized rats. After an i.v. infusion of HU begun in the late G1 phase and continued for periods of up to 30 hr, all hepatocytes scheduled to embark on DNA synthesis in a characteristic intralobular sequence during this time interval accumulated at the G1-S boundary. The effective dose was 1.25 mmoles/kg/hr, preceded by a single injection of 1.69 mmoles/kg. Serum levels of HU rose slightly during continuous infusion and decreased after termination, with a half-life of about 80 min. Liver weight increased during HU infusion. The G1-S blockade was rapidly reversed in the liver after the end of HU infusion. The specific activity of DNA increased to a maximum between 3 and 5 hr. [3H]Thymidine labeling indices reached about 80%. Intralobular distribution of labeled hepatocytes was congruent to the pattern seen in partially hepatectomized rats after a continuous [3H]thymidine infusion of equal duration. The beginning of DNA synthesis in nonparenchymal cells was delayed, as compared with hepatocytes. Vincristine infusion for 12 hr after release from the HU block arrested about 40% of the hepatocytes in mitosis, indicating that a large fraction of cells progressed through the cycle after the prolonged HU block. Partially resected rat liver appeared to be rather resistant to the unfavorable consequences of "unbalanced growth" during the protracted inhibition of DNA synthesis, providing a useful model for synchronization of DNA synthesis in a differentiated resting organ triggered into active growth.

Animals↗

Analysis of cell cycle compartments of hepatocytes after partial hepatecomy.

An analysis of cell kinetic parameters as a function of intralobular localization of hepatocytes was performed using autoradiographic methods to obtain a basis for a quantitative description of cell cycle compartments after partial hepatectomy. The influx into the S compartment revealed a maximum in a lobular zone not immediately adjacent to the portal tract, with a decrease towards the perivenous and periportal area of the lobule. The maximum influx was found in the intermediate zone at 34 hr and a lower one in the perivenous parts of the lobule at 40 hr. The influx pattern at 56 hr was similar to the situation at 18 hr. The fraction of labelled mitoses in the whole liver and in subunits of the lobule disclosed a constant duration of S whereas the duration of G2 + M was prolonged from the periportal to the perivenous zone. A graphical model of kinetic events after partial hepatectomy is proposed, which describes the sizes of the various cell cycle compartments; the model successfully predicted the results of a continuous labelling experiment.

Animals↗

[Cell kinetic studies on the interference between proliferative and functional metabolism in regenerating rat liver after application of phenobarbital (author's transl)].

To investigate the correlation between fuction and proliferation, cell kinetic studies were carried out in regenerating liver of phenobarbital (PB) treated rats. Male adult Wistar rats received i.p. injections of 90 mgPB/kg body weight daily for five days (group A). Rats of group B received additional injections of PB at a reduced dose (30mg/kg) every 12 hrs after partial hepatectomy, starting immediately after the operation. 60 min after a single injection of 3-H-TdR at different intervals after surgery, specific activity of DNA, 3=H=TdR labeling index, and mitotic index were determined. Intralobular distribution of DNA-synthesizing hepatocytes was analyzed in 22 h regenerating liver. Stimulation of fuctional activities by PB results in a transitional synchronization of the start of DNA synthesis in liver parenchymal cells after partial hepatectomy. The labeling indices of group A and B increase to 36% and 30%, respectistribution of DNA-synthesizing hepatocytes revealed that higher levels of synchronization are limited to periportal zones of the liver lobule which provide optimal conditions of G1-S transition. PB treatment apparently does not influence duration of S,G2 or M under these conditions. The results stress the possibility that transitional synchronization of DNA synthesis by functional load might simulate stimulation of growth in a proliferating population.

Animals↗