The estimation of possibility of using order-disorder transition phenomena in Ni, Cu and Au nanoclusters for advancing the efficiency of information recording processes.

The opportunity of transition metals nanoclusters' usage as a data bits in memory devices for the recording transition "order-disorder" has been analyzed. Therefore, with the help of the molecular dynamics method on the basis of TB-SMA potential the simulation of metal nanoparticles (D = 1.6-5.0 nm) crystallization processes have been studied. Influence of various conditions of crystallization on formation of internal structure in metal nanoclusters is investigated. The stability boundaries of various crystalline isomers are analyzed. The obtained dependences are compared with the corresponding data obtained for gold, copper and nickel nanoparticles having similar sizes. Nickel and copper clusters are shown to exhibit common features in the formation of their structural properties, whereas gold clusters demonstrate much more complex behavior. The limiting size of nanoparticles is determined, for which a structural "order-disorder" transition necessary for the data recording is still possible.

p21(WAF1) gene promoter is epigenetically silenced by CTIP2 and SUV39H1.

Mainly regulated at the transcriptional level, the cellular cyclin-dependent kinase inhibitor, CDKN1A/p21(WAF1) (p21), is a major cell cycle regulator of the response to DNA damage, senescence and tumor suppression. Here, we report that COUP-TF-interacting protein 2 (CTIP2), recruited to the p21 gene promoter, silenced p21 gene transcription through interactions with histone deacetylases and methyltransferases. Importantly, treatment with the specific SUV39H1 inhibitor, chaetocin, repressed histone H3 lysine 9 trimethylation at the p21 gene promoter, stimulated p21 gene expression and induced cell cycle arrest. In addition, CTIP2 and SUV39H1 were recruited to the silenced p21 gene promoter to cooperatively inhibit p21 gene transcription. Induction of p21(WAF1) gene upon human immunodeficiency virus 1 (HIV-1) infection benefits viral expression in macrophages. Here, we report that CTIP2 further abolishes Vpr-mediated stimulation of p21, thereby indirectly contributing to HIV-1 latency. Altogether, our results suggest that CTIP2 is a constitutive p21 gene suppressor that cooperates with SUV39H1 and histone methylation to silence the p21 gene transcription.

Peri-operative glucocorticoid replacement therapy in transsphenoidal pituitary adenoma surgery: a prospective controlled study.

BACKGROUND: We set out to prospectively study the peri-operative changes of the hypothalamic-pituitary-adrenal axis (HPA), and to test the hypothesis that the peri-operative corticoid replacement regimen used at the authors' institution in patients with impaired HPA undergoing transsphenoidal pituitary adenoma surgery is adequate. METHOD: Thirty seven patients (21 females, 16 males, mean age 50.6 years) underwent transsphenoidal pituitary adenoma surgery (mean tumour diameter 20.6 mm, 13 tumours hormone-secreting). The HPA functions of these patients were classified as impaired (group A, n = 15) or preserved (group B, n = 22) according to the results of a pre-operative corticotrophin releasing-hormone test (CRHT). Eleven patients (9 female, 2 male, mean age 53.6 years) without pituitary adenomas and with a preserved HPA (as assessed by medical history and morning serum cortisol (MSC) measurements), undergoing decompressive surgery for degenerative lumbar disc disease, were also studied (group C). On the day of surgery, the patients of group A received 100 mg hydrocortisone (HC) replacement therapy, which was thereafter gradually tapered off in a standardised fashion. The patients of groups B and C were not treated with corticoids. Pre-operative, intra-operative and post-operative variables of these three patient groups were compared. FINDINGS: The urinary free cortisol excretion (UFC) in group A declined from 6732 +/- 7683 microg/d on the day of surgery to 305 +/- 358 microg/d on the 10(th) post-operative day. In group B, the respective UFC values were 12,851 +/- 16,278 microg/d and 223 +/- 235 microg/d. In both of these groups, the mean UFC did not fall into the normal range during the first ten post-operative days. On none of the post-operative days, was there a significant difference between the UFC of groups A and B. The UFC values of group C dropped from 177 +/- 157 microg/d on the day of surgery to 87 +/- 61 microg/d on post-operative day six, reaching the normal range from the 2(nd) post-operative day onwards. All UFC values of group C were significantly lower than those of group A and B. None of the evaluated clinical, laboratory and MRI parameters, as disclosed by uni- and multivariate analysis, showed any significant influence on the peri-operative UFC values. CONCLUSIONS: The peri-operative UFC of pituitary adenoma patients with preserved HPA was very high, as compared to patients with degenerative lumbar disc disease. The present study showed for the first time, that the proposed regimen of peri-operative corticoid replacement therapy used in patients with pituitary adenomas and impaired HPA raised cortisol levels to match the physiological increase of UFC in patients with pituitary adenoma surgery and preserved HPA. However, although statistically not significant, the UFC of patients with pituitary adenomas and preserved HPA seemed considerably higher on the day of surgery than in patients with pituitary adenomas and HPA impairment. Although there is no evidence to make it mandatory, administration of 150 mg instead of 100 mg HC substitution on the day of pituitary adenoma surgery in patients with HPA impairment may be prudent.

Dose distribution in hydrocortisone replacement therapy has a significant influence on urine free cortisol excretion.

We investigated the influence of dose distribution in hydrocortisone replacement therapy on urine free cortisol excretion. To this end, we measured 24-hour urine free cortisol (24-h UFC) in 13 patients with hypocortisolism. The patients took 25 mg hydrocortisone/day according to the following schedules: either a single 25 mg hydrocortisone dose at 8:00 a.m., or 15 mg hydrocortisone at 8:00 a.m. and 10 mg hydrocortisone at 2:00 p.m., or 5 mg hydrocortisone at 8:00 a.m., 10:00 a.m., 2:00 p.m., 6:00 p.m. and 10:00 p.m. 24-h UFC decreased significantly with increasing division of the daily 25 mg hydrocortisone dose. When taking 25 mg hydrocortisone in a single morning dose, the mean 24-h UFC was 649 +/- 52 nmol/day (mean +/- SEM). When the daily dose was divided into doses of 15 mg and 10 mg hydrocortisone, 24-h UFC was reduced by 28 % to 466 +/- 39 nmol/day (p < 0.002). After division into five doses of 5 mg, 24-h UFC was reduced by 42.8 % to 371 +/- 36 nmol/day (p < 0.001) compared to the single 25 mg dose. These data demonstrate that consideration of the dose distribution in hydrocortisone replacement therapy when analysing 24-h UFC is of clinical importance.

Endocrinological outcome following first time transsphenoidal surgery for GH-, ACTH-, and PRL-secreting pituitary adenomas.

BACKGROUND: To study remission rates and pituitary functions following transsphenoidal surgery of newly diagnosed GH-, ACTH-, and PRL-secreting pituitary adenomas. METHODS: Out of a series of 329 newly diagnosed pituitary adenomas, 131 (39.8%) were hormone (67 GH-, 27 ACTH-, 37 PRL-) secreting. PRL-secreting adenomas were subjected to surgery because they failed to respond to previous medical treatment therapy. The data on secreting adenomas, regarding the results of standardised endocrinological testing, MRI findings and water metabolism disturbances, were extracted retrospectively from the pituitary data-base of the hospital. The mean follow-up was 3.7 years. RESULTS: The overall remission rate for PRL-secreting adenomas (27%) was significantly lower than for GH- (71.6%) and ACTH-secreting (81.5%) ones. Remission rates correlated negatively with the magnitude of preoperative hormone excess (not in Cushing's disease), tumour size (not in prolactinoma) and invasiveness. Generally, the improvement of the adenopituitary functions was statistically significant during the first three postoperative months, and thereafter remained unchanged. Diabetes insipidus persisting for more than three months occurred with similar frequency in the three patient groups (in 9.4% of GH-, in 6.7% of ACTH-, and in 10% of PRL-secreting adenomas). Tumour regrowth occurred more often in PRL-(20%) than in ACTH- (9.1%) and GH- (0%) secreting tumours. CONCLUSIONS: In GH- and ACTH-secreting pituitary adenomas, remission rates were significantly higher and recurrence rates lower than in PRL-secreting adenomas, which had failed to respond to previous medical therapy. The overall postoperative adenopituitary function was improved in all patient groups. Diabetes insipidus occurred with similar frequency in all patient groups. When reporting on results of surgery for secreting pituitary adenomas, not only remission and recurrence rates, but also the results of the pituitary function should be included.

Expression of the 17beta-hydroxysteroid dehydrogenase type 5 mRNA in the human brain.

An enzyme-mediated metabolism of androgens and estrogens including 17beta-HSD activity in the brain of vertebrates was discovered approximately 30 years ago. Mainly 5alpha-reductase and aromatase have been studied in detail. Recently we could demonstrate reductive and oxidative 17beta-HSD activity as well as considerable mRNA expression of the 17beta-HSD types 3 and 4 in the human brain. In the present study, we report on 17beta-HSD type 5 mRNA expression in brain tissue of women and men. Data analysis did not reveal sex specific differences, but we determined a significantly higher mRNA concentration in the subcortical white matter (SC) than in the cerebral cortex (CX). Investigation of reductive 17beta-HSD in vitro activity with 2 microM androstenedione as the substrate revealed no sex specific differences. Testosterone formation was significantly higher in SC than in CX. Moreover, enzyme activity was significantly higher in brain tissue of adults compared to that of children.