Pregnenolone protects the PC-12 cell line against amyloid beta peptide toxicity but its sulfate ester does not.

Pregnenolone (P), the main precursor of the steroids, and its sulfate ester, pregnenolone sulfate (PS), are the major neurosteroids produced in the neural tissue. Many neuroendocrinological studies stressed the neuroprotective role of neurosteroids although it has been suggested that the inhibition of P and PS synthesis can delay neuronal cell death. The potential roles of P and PS in vital neuronal functions and in amyloid beta peptide (Abeta) toxicity are not clearly identified. This work aims to investigate the effects of P and PS on cell viability and Abeta peptide toxicity in a concentration and exposure time-dependent manner in rat PC-12 cells. The cells were treated with 20muM Abeta peptide 25-35 and variable concentrations of P and PS ranging from 0.5muM to 100muM. To examine the effects of steroid treatment on Abeta peptide toxicity, 0.5muM (low) and 50muM (high) neurosteroids were used. The cell viability and lactate dehydrogenase release of cells were evaluated after 24, 48 and 72h. Morphological changes of cells were also examined. The treatment with higher than 1muM concentrations of P and PS significantly decreased the cell viability comparing to untreated cells. At lower concentrations, P and PS had no toxic actions until 72h. The Abeta treatment resulted in a significant decrease in cell viability comparing to untreated cells. P showed a dose-dependent protective effect against Abeta peptide in PC-12 cells. But its sulfate ester did not have the same effect on Abeta peptide toxicity, even it significantly decreased cell viability in Abeta-treated cells. Consequently, the discrepant effects of P and PS on Abeta peptide toxicity may provide insight on the pathogenesis of Alzheimer's disease.

Effects of transdermal estrogen replacement therapy on plasma levels of nitric oxide and plasma lipids in postmenopausal women.

OBJECTIVE: Our purpose was to assess the effects of transdermal estrogen replacement therapy (TERT) on plasma levels of nitric oxide (NO) and plasma lipids in postmenopausal women. MATERIALS AND METHODS: The study designed as a randomized, double-blind, placebo-controlled trial, involved 43 postmenopausal healthy women who had previously undergone hysterectomy. Women received either transdermal 100 microg 17beta-estradiol (Climara forte TTS) or placebo once a week for 3 months. Plasma levels of NO metabolites, estradiol (E2), total cholesterol (TC), triglicerides (TG), low-density lipoproteins (LDL), high-density lipoproteins (HDL), HDL2 and HDL3 were measured in blood samples of all women which were collected before, after 24 h and after 3 months of therapy. RESULTS: We found significantly increased NO levels 24 h after therapy in TERT group. Moreover significantly higher NO levels were determined at 3rd month of therapy. Serum HDL and HDL2 levels of ERT group were significantly increased at 3rd month of therapy. Alteration of serum levels of HDL3, LDL and TC were not significantly different in groups. TG levels were significantly decreased in TERT group. DISCUSSION: NO-related mechanism may help to explain the cardio-protective effect of TERT in the postmenopausal period. TERT seems to have favorable effects on plasma lipids in surgical menopausal women.

Serum tumor necrosis factor-alpha, glutamate and lactate changes in two different stages of mechanical intestinal obstruction.

BACKGROUND/AIMS: Mechanical intestinal obstruction is a difficult-to-diagnose surgical emergency, especially in the early stage. Clinical and radiological evaluation are the main methods for the diagnosis. Metabolic, inflammatory and ischemic changes occur during intestinal obstruction. No specific biochemical parameters related to diagnosis and severity of intestinal obstruction have been found. In this experimental study, we investigated serum tumor necrosis factor a L-glutamate and L-lactate levels as biochemical markers which reflect physiopathological processes in two different stages of intestinal obstruction. METHODS: Mechanical obstruction was created in Wistar rats with distal ileal ligation. Animals were divided into five groups (Control, Sham-12, Sham-24, Intestinal obstruction 12 and intestinal obstruction-24) and each group consisted of 10 rats. Blood samples were taken 12 and 24 hours after Sham and intestinal obstruction operations. Tumor necrosis factor a levels were measured by ELISA. Serum L-glutamate and L-lactate levels were measured by colorimetric method. RESULTS: Glutamate levels were significantly high especially in the early stage, whereas tumor necrosis factor a increase was significant only in late stage of intestinal obstruction. Serum lactate levels were similar among the groups. CONCLUSION: Serum glutamate levels may have a potential role as a biochemical parameter contributing to diagnosis, especially in the early stages of intestinal obstruction.

Effect of granulocyte-colony-stimulating factor on serum lactate dehydrogenase levels and isoenzymes in a rabbit model.

We investigated the effect of granulocyte-colony-stimulating factor (G-CSF) alone (G-CSF group, n = 7) or after cyclophosphamide (CY) administration (CY+G-CSF group, n = 7) on serum lactate dehydrogenase (LDH) levels and LDH isoenzymes in a rabbit model. In the G-CSF group, an elevation of LDH (all isoenzymes) which was parallel to a sharp increase in leukocyte counts was noted on the first day of G-CSF administration. Despite the increased leukocyte counts on day 5, LDH levels were decreased. In the CY+G-CSF group, the peak elevation of LDH levels, which was prominent in isoenzymes LDH3, LDH4 and LDH5, occurred on day 5 of G-CSF administration and corresponded to the peak levels of leukocytes. In both groups, there was no correlation between LDH levels and leukocyte counts. Our data suggest that an elevation of LDH during the administration of G-CSF may be related to the differentiation of myeloid progenitors.