Biomedical subjects

Jutta Gottschalk

Publications and source records attributed to Jutta Gottschalk.

4 recordsLinked to original sources

PubMed2005

Colorectal cancer metastases affect the biochemical characteristics of the human liver beta-adrenoceptor-G-protein-adenylate cyclase system.

The sympathetic-catecholamine system is involved in the regulation of hepatic metabolic pathways mainly through cAMP-linked beta2-adrenoceptors (beta2-ARs) in humans and to a lesser extent through cAMP-independent mechanisms, but no information is available about the possible biochemical changes of beta2-ARs and their signalling pathways in human colorectal cancer (CRC) and colorectal cancer hepatic metastases (CRCHM). Changes in density and distribution of beta-ARs as well as in post-receptor signalling components were studied in membranes of human liver with CRCHM, and for comparison, in membranes of nonadjacent, non-metastatic human liver (NA-NM) obtained from 13 patients, using binding and competition binding studies. Studies were also carried out using normal and cancerous human colon tissues. In CRCHM, the density of beta-ARs (B(max)) was significantly reduced, compared to NA-NM liver tissues (40.09+/-2.83 vs. 23.09+/-3.24 fmol/mg protein; P<0.001). A similar decrease in the beta-AR density was observed in the colon with primary colorectal cancer compared to healthy colon (37.6+/-2.2 vs. 23.8+/-3.5 fmol/mg protein), whereas the affinity of ICYP binding to the receptor remained unaffected. Desensitized beta-ARs were uncoupled from stimulatory G-protein (G(S)), as total density of beta-adrenoceptors in the high affinity state was significantly reduced. Concomitantly, CRCHM elicited decrease in the catalytic adenylate cyclase (AC) activity (cAMP formation) in response to isoproterenol plus GTP or forskolin or NaF. In NA-NM and CRCHM liver, the inhibition-concentration curves of ICI 118.551 showed the presence of a homogeneous population of the beta2-AR subtypes. Neither the binding patterns nor the inhibition constant (K(i)) of ICI 118.551 were altered in CRCHM. In CRCHM, the hepatic beta-AR-G-protein(s)-AC signalling system was markedly impaired, thus, these changes may well influence beta-AR-mediated functions in both organs.

Adenylyl Cyclases↗

PubMed2005

Evidence for ototopical glucocorticoid-induced decrease in hypothalamic-pituitary-adrenal axis response and liver function.

To clarify whether ototopical glucocorticoid treatment is associated with impaired hypothalamic-pituitary-adrenal axis (HPA) activity and altered hepatic metabolism, one commercially available dexamethasone-containing ointment was tested. At present, very little is known about the effects of ototopical glucocorticoid treatment on HPA and liver function. Ten beagle dogs received two daily therapeutic doses of dexamethasone (0.6 mg/ear) in the outer auditory canal for 21 d in a single-blind, placebo-controlled study. Resting cortisol concentrations were assessed before, during, and after treatment using an RIA system. Adrenal function and HPA feedback sensitivity were measured by a standard dose (250 microg) ACTH stimulation test. Serum biochemical and hematological parameters were measured, whether ototopical glucocorticoids affect hepatic function was studied, and blood cell counts were made. Ototopical dexamethasone treatment induced a marked suppression (to about 100%) of resting plasma cortisol concentrations below the placebo effect (P < 0.0001) within the first 11 d, and these remained reduced during the entire treatment period up to d 19. As well, an ACTH stimulation test found a markedly reduced rise in plasma cortisol concentrations (P = 0.0004). Concomitantly, significant increases in serum activities of alkaline phosphatase, gamma-glutamyl transferase, alanine transaminase, and aspartate transaminase were detected. Moreover, we found a significant reduction in differential leukocyte counts of eosinophils and lymphocytes, whereas neutrophils increased. Although cortisol levels and hematological parameters returned to baseline 7 d after treatment cessation, liver enzyme activities remained elevated. In conclusion, these findings suggest that after ototopical application, dexamethasone is sufficiently absorbed from the auditory canal to suppress HPA function as well as to alter metabolic and hemopoietic profiles. Thus, in long-term treatment of otitis externa or media, the systemic adverse suppression of HPA has to be considered in relation to stress exposure, whereas changes in serum enzyme activities may not be interpreted as hepathopathy.

Administration, Topical↗

PubMedDate not supplied

[The behavior of growth-influencing and steroid hormones in the blood plasma during pregnancy of Awassi sheep in Syria].

In 11 Awassi ewes of a flock of 30 animals continuous investigations were carried out on the changes of somatogenic (growth hormone-GH, prolactin-PRL, insulin-like growth factor I-IGF-I) and steroid hormones (progesterone--PG, estradiol-17 beta-E2) in blood plasma during a gestation period. Eight animals were pregnant (3 with twins), 3 non-pregnant ewes served as control animals. Pregnancy is associated with an increase in the concentrations of the steroid hormones in blood plasma, they decrease markedly already prepartal (PG) or directly at term (E2), reflecting the placental origin of both hormones. Ewes with twins have higher concentrations of both steroid hormones in their blood plasma than animals with a single fetus. During pregnancy the concentrations of IGF-I in blood plasma increase continuously and normalize rapidly after birth. The relationship between the duration of the pregnancy and the concentration of IGF-I can be described by a quadratic regression, further positive correlations exist between the concentrations of IGF-I and PG or E2 in blood plasma, but a negative correlation between IGF-I and PRL. The concentration of PRL diminishes during the gestation, which reflects increasing seasonal influences (decreasing day length and environmental temperature). The concentration of GH shows a steady level throughout the gestation period. Both hormones increase markedly at term, which represents an attendant circumstance of the birth. From all hormones investigated in blood plasma of the ewes only the concentration of IGF-I exhibits a strong positive correlation with the birth weight of their lambs. This can be taken as a first hint to the ability of IGF-I to promote directly the fetal growth.

Animals↗

PubMedDate not supplied

[The behavior of lactogenic and steroid hormones in the blood of Awassi ewes in Syria during lactation].

The concentrations of lactogenic hormones (prolactin--PRL, growth hormone--GH, insulin-like growth factor I--IGF-I) and steroid hormones (progesterone--PG, estradiol--E2) were determined by RIA in the blood plasma of 8 lactating ewes (3 with twins) and compared with that of 3 non-lactating cycling ewes of the same age. All animals live in a flock of 30 Awassi sheep under identical conditions in Syria. The lactation period (192 +/- 25 days) is divided to a suckling period (until day 63) and a hand milking period (2 fold daily) with different levels of milk production (near 2 litres/day in the former, decreasing from 0.8 to 0.1 litre/day in the latter). During the suckling period the concentrations of steroid hormones in the blood plasma are lower, these of lactogenic hormones are higher of lactating than of non-lactating ewes. During the milking period only the concentrations of E2, PRL and IGF-I in the blood plasma of lactating animals are lower than in non-lactating ewes. But, during this time more and more seasonal influences (increasing day length and temperature) overwhelm the influence of lactation on the hormone secretion. Suckling of twins is accompanied with higher levels of E2, PRL and IGF-I in the blood plasma of their mothers than suckling of single lambs. During the lactation period a strong correlation exists between milk yield and the level of GH (r = 0.85) and IGF-I (r = 0.71), a smaller correlations to the level of E2 (r = 0.49) in the blood plasma of the lactating ewes. During the suckling period the milk yield is influenced positively by PRL (r = 0.77) and GH (r = 0.68), but negatively by PG (r = -0.76). During the milking period the milk yield is determined extensively by the level of IGF-I (r = 0.89) in the blood plasma. The concentrations of the analyzed hormones in the blood plasma correlate always positively together.

Animals↗