High levels of C-reactive protein with low total cholesterol concentrations additively predict all-cause mortality in patients with coronary artery disease.

BACKGROUND: This study aimed to investigate independent and additive predictive effects of raised C-reactive protein (CRP) levels and decreased total cholesterol levels on mortality in patients with chronic coronary artery disease (CAD). Low total cholesterol (TC) levels are associated with worsened survival in chronic and acute diseases. Elevated CRP level is an important predictor of vascular events and mortality in patients with CAD. Potential inhibition of immune activation by circulating lipoproteins could be a link between cholesterol and inflammatory markers. MATERIALS AND METHODS: A group of 387 patients (median age 59 years) with CAD and with or without severe heart failure (HF) were followed for a median of 5.06 years. Serum total cholesterol and CRP concentrations were measured at enrollment. RESULTS: The relationship between lipoproteins, CRP and survival was explored. High CRP concentrations were in significant association with severity of HF and predicted worsened survival in patients with CAD (hazard ratio 5.214, 95% CI 1.762-15.427). The association between CRP levels and mortality was independent of potential confounding factors such as age, body-mass index, severity of HF, smoking habits, hypertension and TC levels. The prediction of mortality by low TC levels was significant (hazard ratio 2.932, 95% CI 1.021-8.422). Furthermore, patients with increased CRP and decreased TC (additive predictive effect) phenotype had 11.714-times higher risk (95% CI 2.619-52.385) of being nonsurvivors than patients with low CRP/high TC. CONCLUSIONS: High CRP levels and low TC concentrations are independent and additive predictors of mortality in patients with CAD. Our data indicate that joint analysis of circulating lipoproteins and inflammatory biomarkers may improve prediction of survival in patients with CAD.

Effects of ACTH 1-24 on hydrolysis of beta-casomorphin-4-nitroanilide in brain homogenates in vivo and in vitro.

Administration of ACTH 1-24 to 3-10 days old rats produced a significant decrease in hydrolysis of beta-casomorphin-4-nitroanilide (beta-CM-4NA) in the cytosolic fraction of brain homogenate in the first three hours after injection. Corticosterone treatment did not modify the hydrolysis of the substrate. ACTH 1-24 but not ACTH 4-10, Met-enkephalin or Leuenkephalin given to the brain homogenate resulted in a dose-dependent decrease in liberation of 4NA from beta-CM-4NA. Kinetic data suggest competitive inhibition of ACTH molecule on hydrolysis of beta-CMA-4NA. The ACTH treatment, however, did not influence the hydrolysis of Pro-Gly-4NA or Pro-Pro-4NA in the brain homogenate in vitro.

Changes of enzyme activity in T-cells during induced maternal behaviour in rats.

Continuous exposure to foster pups elicits specific behavioural patterns in adult naive female or male rats. The first exposure induces active avoidance of young. By day 2 or 3 adults show neutral behaviour. Next day complete maternal behaviour begins to develop; e.g. retrieving of pups, nursing and crouching. The avoidance reaction activates stress mechanisms, and the developed maternal behaviour is associated with moderate prolactin release. The question is raised whether pup-induced catecholamine and prolactin release is able to alter enzyme activity in T-cells. Using Arg-Pro-; Leu-Pro; and Pro-Pro-4-nitroanilide as substrates the activity of a marker enzyme dipeptidyl peptidase IV, DP IV, EC. 3.4.14.5., was measured in T-cell suspension prepared from the thymi of adrenalectomized female and male Wistar rats. We found that changes of DP IV activity during the pup-induced avoidance phase could be prevented by propranolol pretreatment indicating the role of catecholamines in this phenomenon. Prolactin released during artificial maternal behaviour in female rats resulted in an elevation of DP IV activity which failed to develop, if they were given daily injections of bromocriptine or apomorphine. It is concluded that pup-exposure is the most physiological way to influence hormonal mechanisms and immune functions, which are highly responsive to sensory stimuli.

[Significance of the determination of estrogen and progesterone receptors in trophoblast diseases]. / Die Bedeutung der Bestimmung von Estrogen- und Progesteronrezeptoren bei Trophoblasterkrankungen.

Binding capacity (Bmax) and affinity (Kd) of cytoplasmatic estradiol and progesteron receptors were determined in trophoblastic tissue and in decidual endometrium by the authors. Results in normal and pathological endometrium and in mature placenta tissue were compared. Both estrogen and progesteron receptors were proved to exist in the decidual endometrium nearest to the molar tissue. Their binding parameters are similar to those in normal endometrium. No progesterone receptors were found in the molar tissue. Binding capacity of estrogens were found to be similar to that of the normal mature placenta. The lack of progesterone receptors might be an etiological factor in the pathogenesis of trophoblast diseases.

Dipeptidyl peptidase IV (DP IV) and superoxide dismutase activity in thymus-derived lymphocytes: effects of inhibitory peptides and Zn2+ in vitro.

DP IV and superoxide dismutase (SOD) activity in thymus-derived lymphocytes of rats was assayed in vitro. The DP IV activity was measured fluorimetrically by hydrolysis of Leu-Pro-AMC, and the SOD activity by the inhibition of autooxidation of L-adrenaline. In order of their competitive inhibitory potency the following peptides were tested against DP IV and SOD activity: Ile-Pro-Ile (diprotin A), Val-Pro-Leu (diprotin B), Ile-Pro, Leu-Pro, Val-Pro, Tyr-D--Ala-Ala-Pro, Phe-Pro, Tyr-Pro, Ala-Ala-Pro and Gly-Pro. The peptides, in the order of their potency against DP IV, were effective to inhibit the SOD activity in T lymphocytes. Zn2+ ions exerted an inhibition on both DP IV and SOD activity in a near equimolar concentration. The involvement of Zn2+ as well as the peptides liberated by hydrolysis of polypeptides in regulation of cell-mediated immune responses has been discussed.

Changes of dipeptidyl peptidase (DP IV) activity in the T lymphocytes of rats following administration of ACTH, dexamethasone and opiates.

The aim of the work was to study the effect of glucocorticoids, opiates and stressful stimuli on dipeptidyl peptidase IV (DP IV, EC 3.4.14.5) activity of T lymphocytes prepared from the thymus of intact and adrenalectomized rats. Four week old male rats of Wistar strain were used. The in vivo administration of ACTH, dexamethasone and morphine treatment resulted in an increase of DP IV activity in the cell suspension. In adrenalectomized rats ACTH treatment failed to modify the enzyme activity, however, pain or emotional stress resulted in an elevated DP IV activity. Morphine and D-Met2-Pro5-enkephalinamide resulted in a dose dependent activation of DP IV in T cells, an effect which could be modified by naloxone pretreatment. Our findings show that DP IV mechanisms in T cells are highly sensitive to exogenous and endogenous steroids, opiates and biologically active substances released in response to stress in rats.

Comparative analysis of enzyme activity in human colostrum, milk, and serum.

Changes of enzyme activity in the colostrum, milk, and serum samples of 14 mothers were followed. For the enzyme assay, the colostrum and the milk samples were diluted, 1:10 and 1:5, respectively. The activity of the following enzymes were measured: lactate dehydrogenase (LDH); gammaglutamyl transpeptidase (GGT); aspartate aminotransferase (ASAT); alanine aminotransferase (ALAT); cholinesterase; alkaline, and acid phosphatase. Milk, LDH, ASAT, and ALAT activities did not change during the first four days of lactation, yet were significantly higher than the corresponding activities of serum. The activity of GGT and alkaline and acid phosphatase in milk showed a marked decrease by day 4 postpartum; however, the GGT stayed much higher than that of serum, while the activity of the other two enzymes decreased to the level of the serum. By contrast, as compared to the colostrum, the cholinesterase activity in the breast milk showed a significant increase.

Superoxide dismutase activity in thymus cell suspension: effects of methionine-enkephalin and morphine.

Superoxide dismutase activity of rat thymus-derived cells was studied by the inhibition of L-adrenaline auto-oxidation oxidation in vitro. The incubation of cells in the presence of methionine-enkephalin (Met-Enk) or morphine (2-20.10(-7) M and 2-8.10(-6) M, respectively) was performed in Krebs-bicarbonate buffer at 37 degrees C for 180 min. After a lag period of 30 to 60 min of incubation, both Met-Enk and morphine decreased the inhibitory activity of cell suspension on the adrenaline autooxidation. Naloxone blocked the effects of opioids in near equimolar concentrations. The observations suggest the interaction of opioids on superoxide anion production of T cell lymphocytes.