Effects of short- and long-term dexamethasone treatment on growth and growth hormone (GH)-releasing hormone (GRH)-GH-insulin-like growth factor-I axis in conscious rats

Although the inhibitory effects of a chronic excess of glucocorticoids (GC) on body growth and GH secretion are well established, the mechanisms involved remain unclear. In this study, we examined the chronic effects of a high dose of dexamethasone (DEX) on spontaneous GH secretion and insulin-like growth factor (IGF)-I in conscious rats. The animals were given daily i.p. injections of DEX (200 microg/day) for either one or four weeks. Body growth assessed by tibia length and serum IGF-I levels was significantly inhibited 1 week after treatment. By contrast, spontaneous GH secretion was not altered 1 week after the treatment. Neither hypothalamic GRH and somtatostain mRNA levels nor GH responses to GRH from single somatotropes were affected 1 week after the treatment. Four weeks after DEX treatment, body growth of the rats was noticeably suppressed. Interestingly, spontaneous GH secretion, hypothalamic GRH mRNA levels and GH responses to GRH were all inhibited 4 weeks after treatment. Pituitary GRH receptor mRNA levels were not altered 1 week after treatment, but increased after 4 weeks. These results indicate that a high dose of DEX initially impairs IGF-I production and subsequently inhibits spontaneous GH secretion in rats. Inhibition of spontaneous GH secretion resulting from chronic GC excess is due, at least in part, to the impairment of hypothalamic GRH synthesis and pituitary GH responsiveness. An increase in the pituitary GRH receptor may be caused by decreased GRH secretion.     

The significance of urinary N-acetyl-beta-D-glucosaminidase for predicting early stage diabetic nephropathy

We studied urinary N-acetyl-beta-D-glucosaminidase (NAG) in the early stage of diabetic nephropathy in 27 non-insulin-dependent diabetes mellitus (NIDDM) patients with a microalbumin level below 20 mg on 24-hour urine sample. Microalbumin and NAG excretion were measured in 24-hour urine samples collected on three separate occasions within seven days of admission. Creatinine clearance was determined simultaneously. There was a significant negative correlation between the creatinine clearance and 24-hour urinary NAG (r = -0.38, p < 0.05). Elevation of urinary NAG may indicate decreased renal function during early stage NIDDM nephropathy.     

Pharmacokinetic and bioequivalence study of two gemfibrozil preparations

A comparative pharmacokinetic study has been performed in 19 healthy male volunteers in a single-dose, randomized, two way cross-over design with two preparations of gemfibrozil (CAS 25812-30-0) capsules each of them containing 300 mg active ingredient. The test preparation was Innogem 300 mg capsule. The plasma concentration of gemfibrozil was determined by a validated HPLC-UV analytical method. The statistical comparison of individual pharmacokinetic parameters (AUC0-16, AUC0-oc Cmax, tmax) of the two capsule preparations was performed by three-way analysis of variance (ANOVA), Wilcoxon's, Westlake's, Schuirmann's and Hanck-Anderson's method as well as by the calculation of confidence intervals on the ratio of test/reference. The relative bioavailability of the test preparation with respect to the reference preparation in terms of the AUC0-oc was 104.06 +/- 21.61%. No statistically significant difference was found between the pharmacokinetic parameters, calculated from plasma concentration-time curves, indicating that the two preparations were bioequivalent.     

Bladder pseudotumor in childhood

The application of frozen and radiation sterilized allogenic bone grafts for reconstructions in orthopaedic operations is described. Analysis of results of treatment of 1125 patients was performed. It was found that use of preserved bone allows to reduce the extend and duration of surgery. Nearly total substitution of grafts may be seen in 3 to 8 months after surgery.     

Ethical, legal and medical aspects of transplantation

Tissue and organ transplantation is a very complex interdisciplinary treatment, particularly in regard to unpaired organs, and it carries numerous risks for all participants in such an action. For the purpose of minimizing the risks to the allowed level and the preservation the humanitarian goals in medicine when performing the transplantation, professional and scientific doctrines and the respect of ethical and legal principles should be strictly observed. The paper presents the basic approaches in the estimation of justification, usefulness and certain forms of responsibility in the process of transplantation. Ethical and legal postulates which support transplantation to prevent deviation, deprivation or delinquency have also been reviewed.     

Subcutaneous soft tissue tumours at the site of implanted microchips in mice

An experiment using 4279 CBA/J mice of two generations was carried out to investigate the influence of parental preconceptual exposure to X-ray radiation or to chemical carcinogens. Microchips were implanted subcutaneously in the dorsolateral back for unique identification of each animal. The animals were kept for lifespan under standard laboratory conditions. In 36 mice a circumscribed neoplasm occurred in the area of the implanted microchip. Females were significantly more frequently affected than male mice. An influence of age or different treatment on the s.c. tumour incidence in two mice generations could not be observed. Macroscopically, firm, pale white nodules up to 25 mm in diameter with the microchip in its center were found. Microscopically, soft tissue tumours such as fibrosarcoma and malignant fibrous histiocytoma were detected.     

Intelligent control of the feeding of aluminum electrolytic cells using neural networks

To be efficient, the control of alumina feeding of the electrolytic cell must be based on cell resistance, alumina concentration, and cell state. Most control schemes now in use are based on cell resistance only, and, thus, constitute an open-loop control that lacks robustness because their decision criteria are not explicitly tied to concentration nor to cell state. This results in the cell operating at nonoptimal concentrations, and cell efficiency is diminished. An optimal operation requires a knowledge of concentration and an adjustment of the decision criteria as a function of concentration. A learning vector quantization (LVQ) type of neural network was built and trained to recognize the cell state. Knowing the state of the cell and its resistance, concentration can be estimated using predetermined regression functions. The decision criteria for the control logic are then consequently adapted. A closed-loop control scheme is thus obtained. Results show that, with its control so structured, the cell can operate at or near optimal concentrations independently of its state. This flexible and intelligent character of the neural control can provide a considerable advantage as compared to the standard control.     

Immunostimulatory DNA: sequence-dependent production of potentially harmful or useful cytokines

Certain bacterial immunostimulatory (i.s.) DNA sequences containing unmethylated CpG motifs stimulate antigen-presenting cells (APC) to express a full complement of costimulatory molecules and to produce cytokines including interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha. While IL-12 is key to their T helper cell (Th)1-promoting adjuvant activity, secretion of toxic levels of TNF-alpha is harmful in that it promotes toxic shock. Given the beneficial as well as harmful consequences of i.s. DNA, we investigated the possibility of identifying DNA sequences, i.e. CpG oligodeoxynucleotides (ODN) which differentially activate IL-12 versus TNF-alpha cytokine production in APC. Here, we describe an i.s. DNA sequence with these characteristics. While its potential to induce IL-12 is preserved, its ability to trigger TNF-alpha release is strongly curtailed both in vitro and in vivo. I.s. DNA could be segregated into lethal and non-lethal in a mouse toxic shock model. The non-toxic i.s. DNA was useful as an adjuvant, thus allowing cytotoxic T cell responses to the soluble protein ovalbumin and conferring a resistant Th 1 phenotype to BALB/c mice lethally infected with Leishmania major. This i.s. CpG motif may thus be prototypic for a useful immunostimulating DNA sequence that lacks harmful side effects.