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Biomedical subjects

W Schramm

Publications and source records attributed to W Schramm.

At least 181 records · Page 10Linked to original sources

Combined toxic effects of tetracycline and ethinyl estradiol on liver function of mice.

The combined effects of ethinyl estradiol (EE) (0.5 micrograms/g s.c. once daily for 4 days) and tetracycline (TC) or doxycycline (DC) (50 micrograms/g i.v.) on liver weight and water content, serum transaminases, alkaline phosphatase, urea, triglycerides, and cholesterol as parameters of various liver functions were investigated in mice. It became apparent that depending on the parameter tested synergistic and antagonistic effects may occur, e.g., synergistic effects were observed with the serum transaminases and liver cholesterol; antagonistic effects were seen with the serum urea and serum cholesterol.

Alanine Transaminase↗

Rapid recovery of nuclear estrogen receptor and oxytocin receptor in the ovine uterus following progesterone withdrawal.

We previously showed that progesterone rapidly down regulates nuclear estrogen receptor (Re) in the estrogen-primed rodent uterus. We have now extended these studies to test the response of the Re system in sheep uterus to progesterone withdrawal. Since the estrogen-Re complex is believed to regulate hormone-dependent gene expression, it was of interest to determine whether withdrawal of progesterone under constant estrogen stimulation would lead to the recovery of nuclear Re levels and estrogen action, i.e. oxytocin receptor (ROT) synthesis. Ovariectomized ewes were primed with estradiol-17 beta and serum steroid levels were maintained by constant infusion of estradiol (0.5 microgram/h) and progesterone (500 micrograms/h) for 5 days. The animals were anesthetized with fluothane/O2, and uterine samples were excised 1 h before and 3, 6 and 12 h after progesterone withdrawal. Estradiol infusion was continued during the experiment in order to maintain estrogen levels at a steady state (14 pg/ml plasma). Re, ROT and progesterone receptor (Rp) were measured in endometrium and myometrium using standard 3H-hormone binding assays. Following progesterone withdrawal, the nuclear Re concentration increased in both uterine compartments, and the nuclear Re level was correlated significantly with the ROT concentration in the membrane fraction of both uterine tissues (endometrium, r = 0.79; myometrium, r = 0.86). Although cytosol Re rose between 6 and 12 h in the endometrium, cytosol Re levels remained unchanged in myometrium. Cytosol Rp appeared to increase in endometrium but not in myometrium. Uterine tissue sampled from a control animal before stopping the progesterone infusion revealed that the observed changes in receptor concentration following progesterone withdrawal were not due to regional differences in receptor levels. These results demonstrate that the recovery of nuclear Re in the ovine endometrium and myometrium following progesterone withdrawal represents a selective effect on Re retention in the nucleus rather than on cytosol Re availability or Re activation which was controlled by constant estrogen infusion. Thus, these results are consistent with the hypothesis that progesterone induces an Re regulatory factor which acts to down regulate nuclear Re, and that the activity of this factor diminishes rapidly after progesterone withdrawal.

Animals↗

Released granulocytic elastase: an indicator of pathobiochemical alterations in septicemia after abdominal surgery.

To discover the role of lysosomal enzyme release from polymorphonuclear (PMN) leukocytes during septicemia, plasma levels of PMN elastase were measured with a newly developed enzyme-linked immunosorbent assay for detection of the PMN elastase-alpha 1-proteinase inhibitor complex (E-alpha 1PI). Plasma samples from 41 patients were assayed continuously before and after major abdominal surgery. The patients were divided into a group without infection (group A) and two septicemia groups (survivors in group B and nonsurvivors in group C). The E-alpha 1PI levels of the 11 patients in group A without any signs of pre- or postoperative infection were in the normal range (a normal value of 86.5 +/- 25.5 ng/ml has been reported in 153 healthy subjects), except for a small increase to 208.8 +/- 25.6 ng/ml 12 hours after surgery. When septicemia was confirmed clinically in patients in groups B and C, the E-alpha 1PI levels rose on average to six times the norm in group B (649.9 +/- 116.3 ng/ml) and to more than 10 times the norm in group C (985.0 +/- 154.6 ng/ml). Peak values greater than 2,200 ng/ml could be measured in both groups. In patients in group B, the E-alpha 1PI levels returned to normal during recovery, while in those in group C they remained significantly elevated (560.5 +/- 174.7 ng/ml) until death. Correlations were demonstrated between the amount of elastase released into the circulation and the decrease in the activities of antithrombin III, coagulation factor XIII, and alpha 2-macroglobulin, as well as the increased C-reactive protein in plasma. We conclude that release of elastase and other lysosomal factors from PMN cells plays a major role in the pathobiochemical alterations during septicemia. In addition, significantly elevated E-alpha 1PI levels in the postoperative course seem to be a suitable indicator for onset and persistance of sepsis as well as of the severity of this disorder in patients after major surgery.

Abdomen↗

Expansion of a minor subpopulation of peripheral blood lymphocytes (T8+/Leu 7+) in patients with haemophilia.

Immunological analysis of peripheral blood mononuclear cells (PBM) was performed in 20 patients with haemophilia A or B. One of the patients had never received clotting factor substitution in his life. Six different sources of lyophilized clotting factor were used for the other patients, but every given patient received factor from one source, exclusively. None of the patients exhibited lymphadenopathy and only one suffered from local bacterial infection. Mononuclear cell counts were within the normal range and mitogen stimulation with phythaemagglutinin (PHA) and concanavalin A (Con A) was found normal in all but two patients. Ratios of helper and suppressor cells (T4/T8) were below 1.0 in 10 of the patients. Some of these patients had a relative increase of T8+ cells and at the same time of Leu 7+ (natural killer (NK)/suppressor) cells. Double-marker analysis revealed that the subpopulation of cells expressing both the T8 and the Leu 7 antigen, which on the average accounted for 2.1% of the mononuclear cells in controls, was increased 4.5 fold (9.1%) in haemophilia patients. One patient exhibited 37.8% T8+/Leu 7+ double-marker cells. VEP13+ cells (active NK cells) were decreased below the normal range in 11 of the patients. Abnormal values for lymphocyte subsets were found in every treatment group. The patient who had never received any clotting factor exhibited normal values in all respects. In an additional set of patients, those with increased percentage of T8+/Leu 7+ cells exhibited decreased NK cell activity indicating that the T8+/Leu 7+ cells are not active NK cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

The structure of steroids and their diffusion through blood vessel walls in a counter-current system.

Several substances including prostaglandin F2 alpha, progesterone and 85-krypton have been shown to be transferred from the venous side to the arterial side of the circulation in the ovarian vascular pedicle. Experiments were therefore carried out to study the transfer of three pairs of steroids (progesterone and 20 alpha-dihydroprogesterone, C-21; androstenedione and testosterone, C-19; and estrone and estradiol-17 beta, C-18) in which each member of a pair differed by one hydroxyl group. Each pair of steroids, one labeled with 3H and the other with 14C, were infused in sequence for 30 minutes into a side branch of an ovarian vein near the hilus of the ovary with a rest period of 90 minutes between infusions. An increase in radioactivity in ovarian arterial plasma compared to the radioactivity in an equal volume of aortic plasma sampled simultaneously was used as the index for a direct transfer of steroids from the ovarian vein to the adjacent ovarian artery. All six steroids showed such a transfer which began 3 to 6 minutes after the start of each infusion and decreased rapidly after the infusion was stopped. The results of this study also showed that a larger quantity of the less polar (ketonic) form of each steroid pair examined was transferred than its hydroxyl counterpart.

Androgens↗

Effect of four primary prostaglandins and relaxin on blood flow in the ovine endometrium and myometrium.

The effect of the prostaglandins (PG) D2, E2, F2 alpha and I2 (infusions of 250 ng/min for 10 min into the uterine artery) and relaxin (1 microgram/min) on uterine contractions and on the myometrial and endometrial blood flow to the uterus of ovariectomized, estrogen-primed ewes was investigated. The 85Kr clearance method was used to measure blood flow. PGD2 and PGI2 increased both myometrial and endometrial capillary blood flow, whereas PGE2 and relaxin did not. PGF2 alpha reduced the myometrial blood flow only at a significance level of P less than 0.1 but induced no significant changes in the endometrial flow. PGE2, PGF2 alpha and, notably, PGD2 caused a uterine hypertonus. PGI2 and relaxin did not affect the uterine motility. There is a parallel effect of the investigated substances on the blood flow of myometrium and endometrium but PGD2 induces contractions of the smooth muscle cells in the myometrium while relaxing comparative cells in blood vessels.

Animals↗

Effect of exogenous ovine placental lactogen on luteolysis induced by prostaglandin F-2 alpha in sheep.

The ability of ovine placental lactogen (oPL) to stimulate progesterone secretion by the ovary as well as its ability to protect the corpus luteum against the luteolytic action of PGF-2 alpha was investigated. When oPL was infused alone into the ovary for 2 h on Day 12 of an induced cycle at rates of 0.6, 6.0, 30.0 or 60.0 micrograms/h there was no significant increase in progesterone secretion by the autotransplanted ovary in 7 sheep. An extension of the infusion of oPL did not prevent luteal regression during the administration of PGF-2 alpha given either continuously (10 micrograms/h for 6 h, 5 sheep) or as 5 pulses each lasting 1 h and of increasing concentration in 25 h (2 sheep). We conclude that oPL does not (a) stimulate progesterone secretion when infused directly into the arterial supply of the ovary or (b) have any direct protective effect against the luteolytic action of PGF-2 alpha on the ovine CL.

Animals↗

[Postpartum streptococcal gangrene].

A case of acute hemolytic streptococcal gangrene is presented. Typical signs of this disease are local pain, erythema, edema, formation of blisters, and gangrene. Malaise and fever are more unspecific. The special clinical feature of this postpartum case is discussed and compared with the literature. The therapy comprised extended incision of the vulva, application of antimicrobial agents, and exchange transfusion.

Acute Disease↗

Corpus luteum regression induced by ultra-low pulses of prostaglandin F2 alpha.

In view of the pulsatile nature of PGF2 alpha secretion from the ovine uterus at the time of luteolysis, experiments were designed to examine the effect of pulsed infusions of PGF2 alpha on luteal function and to re-examine the minimal effective levels of PGF2 alpha required to induce luteolysis. To mimic physiological conditions, hour-long infusions of PGF2 alpha in increasing concentrations were given either 4 times in 19 h or 5 times in 25 h into the arterial supply of the autotransplanted ovary in conscious sheep on day 12 of an induced cycle. Blood flow and progesterone secretion rate from the ovary were used to monitor directly the luteolytic effect of administered PGF2 alpha. The concentration of LH in peripheral plasma was measured throughout each infusion experiment and the presence of a preovulatory peak of LH was used as an indicator of the permanence of luteal regression. Four pulses of PGF2 alpha in 19 h caused complete corpus luteum regression in only 1 of 4 animals whereas the addition of a fifth pulse (5 pulses in 25 h) caused permanent regression in 4 out of 4 animals. Infusion of 5 hour-long pulses of saline or PGF2 alpha at a rate less than 0.04 microgram/h did not induce permanent suppression of progesterone secretion. The average total effective dose of PGF2 alpha required to induce luteal regression when given as 5 pulses was 1/40th of the amount currently regarded as the minimal effective one when given by constant infusion into the ovarian artery. In another series of experiments the luteolytic effect of a single hour-long pulse of 0.1 microgram/h PGF2 alpha given daily for either 3 or 4 days was investigated. A significant fall (ANOVA, F0.01) in progesterone secretion rate, which reached a nadir at 5.3 +/- 2.2 h (means +/- S.D., n = 15), was followed by a recovery of progesterone secretion rate. Permanent luteal regression did not occur with this protracted regimen, suggesting that a relatively short pulse frequency of PGF2 alpha over a minimal period of 24 h is a necessary condition for physiological regression of the corpus luteum in sheep.

Animals↗

Platelet enzyme activities in diabetes mellitus in relation to endothelial damage.

Increased platelet reactivity has been suggested in the pathogenesis of both arteriosclerosis and diabetic microangiopathy. Therefore, platelet function and platelet enzyme activities were assessed in a large group of 357 diabetics (256 patients with IDDM, aged 16-49 and 101 patients with NIDDM, aged 50-78) and 163 matched controls, and related to photographically documented retinopathy (Rd) and to peripheral vascular disease (PVD) as well as to plasma levels of von Willebrand factor (VIII R:Ag) as an indicator of endothelial damage. Patients with IDDM had increased platelet aggregation (PA, expressed as microM ADP threshold concentration) before Rd was detectable in comparison to control subjects (P less than 0.01). PA was further increased in patients with advanced Rd (P less than 0.01), whereas 20 newly diagnosed diabetics with IDDM exhibited normal PA. Patients with minimal Rd did not differ from patients without Rd. Plasma beta-thromboglobulin (reflecting platelet consumption in vivo) was enhanced significantly in patients with Rd only (P less than 0.05), as was malondialdehyde (MDA) production of platelets (as a measure of platelet endoperoxide formation). Factor VIII-related antigen in plasma was already increased in patients without Rd (P less than 0.05), yet more so in patients with Rd (P less than 0.01). Prostacyclin-stimulated adenylate cyclase activity (ACA) of platelets (as an antiaggregatory enzyme system) was twice as high in diabetics with advanced Rd compared with patients without Rd and with controls (P less than 0.01). Significant correlations were found between PA and plasma F VIII R: Hg, MDA production, and ACA of platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗

[Experiences with the substitution of antithrombin III concentrates in congenital and acquired deficiency disorders].

Antithrombin III (AT III) is the most important inhibitor for factor X and thrombin. Hence, it essentielly influences the regulation of haemostasis. In the aetiology of AT III decreases, hereditary as well as acquired deficiencies can be differentiated. With the exception of patients with hereditary AT III deficiency it is not possible to define the heavy tendency of thrombosis clearly on a biochemical basis. Acquired AT III decreases lead much often to clinical relevant problems than the congenital ones. Since 1974 we substitute AT III using AT III concentrates. The evaluation of the clinical success was often impeded due to the polypragmatic additional therapy. Well-founded and strict indications for the substitution of AT III with a therapeutical concentrate are acute macro- and microthrombosis with decreased AT III levels, e.g. in severe thromboembolic diseases and in hereditary AT III deficiencies. Concerning other clinical pictures with acquired AT III deficiency, a substitution may be indicated very reasonably, however, further studies are necessary to prove this.

Aged↗