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Biomedical subjects

G Jahnke

Publications and source records attributed to G Jahnke.

13 recordsLinked to original sources
PubMed2002

Interference by toxic metal ions with zinc-dependent proteins involved in maintaining genomic stability.

Metal ions are essential components of biological systems; nevertheless, even essential elements may have toxic or carcinogenic properties. Thus, besides As(III) and Cd(II), also Ni(II) and Co(II) have been shown previously to disturb different types of DNA repair systems at low, non-cytotoxic concentrations. Since some metals exert high affinities for SH groups, we investigated whether zinc finger structures in DNA-binding motifs of DNA repair proteins are potential targets for toxic metal ions. The bacterial formamidopyrimidine-DNA glycosylase (Fpg protein) involved in base excision repair was inhibited by Cd(II), Cu(II) and Hg(II) with increasing efficiencies, whereas Co(II), As(III), Pb(II) and Ni(II) had no effect. Furthermore, Cd(II) still disturbed enzyme function when bound to metallothionein. Strong inhibition was also observed in the presence of phenylselenyl chloride, followed by selenocystine, while selenomethionine was not inhibitory. Regarding the mammalian XPA protein involved in the recognition of DNA lesions during nucleotide excision repair, its DNA-binding capacity was diminished by Cd(II), Cu(II), Ni(II) and Co(II), while Hg(II), Pb(II) and As(III) were ineffective. Finally, the H(2)O(2)-induced activation of the poly(ADP-ribose)polymerase (PARP) involved in DNA strand break detection and apoptosis was greatly reduced by Cd(II), Co(II), Ni(II) and As(III). Similarly, the disruption of correct p53 folding and DNA binding by Cd(II), Ni(II) and Co(II) has been shown by other authors. Therefore, zinc-dependent proteins involved in DNA repair and cell-cycle control may represent sensitive targets for some toxic metals such as Cd(II), Ni(II), Co(II) and Cu(II), as well as for some selenium compounds. Relevant mechanisms of inhibition appear to be the displacement of zinc by other transition metals as well as redox reactions leading to thiol/disulfide interchange.

Cations, Divalent↗
PubMed1999

Maternal and developmental toxicity evaluation of melatonin administered orally to pregnant Sprague-Dawley rats.

Melatonin (MEL) is a widely used, over-the-counter sleep aid, and it has putative contraceptive, antioxidant, antiaging, and anticancer effects. The developmental toxicity potential for repeated oral doses of MEL had not previously been evaluated. In the present studies, time-mated, Sprague-Dawley-derived (CD) rats were administered MEL or vehicle by gavage on gestation days (gd) 6-19. MEL-treated groups received 1-, 10-, 100-, 150-, or 200-mg/kg body weight/day in the screening study (15 rats/group), and 50, 100, or 200 mg/kg/day in the definitive study (25 rats/group). In both studies, maternal food/water consumption, body weight, and clinical signs were monitored at regular intervals throughout gestation. At termination (gd 20, both studies), maternal liver and gravid uterine weights, number of ovarian corpora lutea, conceptus survival, fetal sex, and fetal body weight were evaluated. Fetal morphological examination included external structures (both studies) as well as visceral and skeletal structures (definitive study). In the screening study, maternal serum levels of 17beta-estradiol, progesterone, prolactin, and luteinizing hormone were determined by radioimmunoassay, and mammary tissue was fixed, stained, and evaluated for percent glandular area within the fat pad. No maternal morbidity/mortality was found in either study. In the screening study, aversion to treatment (> or =100 mg/kg/day) and reduced maternal weight gain (> or =150 mg/kg/day) were noted, but reproductive/endocrine parameters and fetal development were not affected. In the definitive study, aversion to treatment was noted at > or =50 mg/kg/day, and mild sedation, reduced maternal food intake, and reduced body weight gain were found during initial treatment with 200 mg/kg/day. MEL had no effect on prenatal survival, fetal body weight, or incidences of fetal malformations/variations. Thus, in the definitive study, the maternal toxicity NOAEL and LOAEL were 100 and 200 mg/kg/day, respectively, and the developmental toxicity NOAEL was > or =200 mg/kg/day.

Animals↗
PubMed1989

Hyaluronate binding to intact corneas and cultured endothelial cells.

Sodium hyaluronate (HA) protects the corneal endothelium during cataract surgery. Recently, HA receptors have been found on liver endothelial cells that play an important role in HA catabolism. It is unknown if similar receptors are present on the corneal endothelium. In this study we have used two different methods to follow the interaction of HA with corneal endothelial cells: (1) binding of 3H-HA to cells or intact corneas was determined in the presence or absence of unlabelled glycosaminoglycans after solubilization with KOH, and (2) the HA-binding region of bovine cartilage proteoglycan was used as a histochemical probe and visualized by an avidin-biotin method. 3H-HA bound both to intact rat corneas pretreated with Streptomyces hyaluronidase and to cultured monkey corneal endothelial cells. The fraction-bound 3H-HA increased with time and was saturable. Cultured endothelial cells were estimated to have 1700-2100 binding sites per cell with a binding constant of 5.6-8.5 X 10(9) liters/mol. Furthermore, unlabelled HA displaced the tritiated in a dose-dependent manner and the displacing efficiency was dependent on molecular weight. The histochemical method disclosed that HA forms a continuous layer on the endothelium. If Healon was injected into the anterior chamber, the thickness and staining intensity of this layer increased conspicuously.

Animals↗
PubMed1980

Studies of the neural mechanisms by which hypothyroidism decreases prolactin secretion in the rat.

These studies report that chronic hypothyroidism in the rat is accompanied by decreased serum prolactin. An investigation of those mechanisms by which hypothyroidism decreases prolactin secretion revealed the following findings: (1) activation of tyrosine hydroxylase in the median eminence (ME) and increase in the turnover-rate of dopamine (DA) in the ME; (2) a decreased content and in vitro release of prolactin by pituitaries from hypothyroid rats; (3) decreased [3H]spiroperidol binding to pituitary homogenates obtained from hypothyroid rats, and (4) normal increase of serum prolactin following administration of haloperidol. Comparison of the effects of hypothyroidism on dopaminergic terminals of the striatum with those of the ME was made and the following tentative conclusions proposed. Hypothyroidism presumably increases the release of DA into the pituitary portal system. A deficiency of thyroid hormone desensitizes the pituitary lactrotrope to inhibition by DA, decreases the total pituitary prolactin content and presumable also reduces the peripheral catabolism of prolactin. The overall net effect of hypothyroidism is, therefore, a decrease in serum prolactin levels which can increase normally following haloperidol. The mechanism by which a deficiency of thyroid hormone alters the function of the tuberoinfundibular and striatal dopaminergic systems is unknown.

Animals↗
PubMed1980

Decreased serum 3,5,3'-triiodothyronine and thyroxine levels accompanying acute and chronic ritalin treatment of developing rats.

Basal serum levels of T3, T4, and TSH and the serum TSH increment after TRH are reported for rats chronically or acutely treated with ritalin. Serum levels of T3 and T4 are significantly reduced in rats chronically treated with ritalin twice daily for 21 days. Female rats appear to be more susceptible than males to the suppressive action of ritalin. Ritalin appears to accelerate the circulatory clearance of serum T3 and T4. Basal serum levels of TSH demonstrate graded elevations after sequentially higher doses of ritalin and, in most cases, hypophyseal responsivity (delta TSH) to TRH challenge appears to be marginally enhanced by chronic ritalin treatment. Thyroidal responsiveness is not adversely affected by chronic ritalin treatment. Serum T3 and T4 levels return to normal levels after chronic ritalin treatment is discontinued; however, the maturational rise of the basal serum level of TSH is permanently depressed in 35 and 100 mg/kg BW ritalin-treated males. Acute administration of ritalin (35 or 100 mg/k BW) results in a significant reduction of the serum levels of T3 and T4 within 5 h and depressed levels persist for 18 days.

Aging↗
PubMed1978

Cholecystokinin inhibits tail pinch-induced eating in rats.

Peripheral administration of the COOH-terminal octapeptide of cholecystokinin in doses from 1 to 100 micrograms per kilogram of body weight (0.25 to 25.0 micrograms per rat) significantly antagonized tail pinch-induced eating in rats, an animal model for stress-induced human hyperphagia. Centrally administered cholecystokinin was effective only in high doses (3 micrograms into the cerebral ventricle). The finding that the minimal effective dose of cholecystokinin in suppressing stress-induced appetitive behavior is smaller after peripheral than central administration suggests that the peptide is acting on peripheral, as opposed to central nervous system, substrates.

Animals↗