Occurrence of osteopenia among adolescent girls with oligo/amenorrhea.

The occurrence of reduced bone mineral density (BMD) among adolescent girls with oligomenorrhea or secondary amenorrhea, due to 'pure' dysfunction of the hypothalamo-pituitary-ovarian (HPO) axis (without anorexia nervosa, excessive sport or ballet, slimming diet, etc.) was examined. The study group consisted of 19 adolescent girls (age 16-18 years) with oligo/amenorrhea. Clinical (height, weight, age at menarche, duration of amenorrhea, body mass index (BMI)), hormonal (follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, testosterone, prolactin), and ion (calcium, sodium, potassium, phosphate, chloride) parameters and the BMD of the lumbar spine were investigated. Correlations between BMD and other parameters were also examined. Twenty healthy volunteers (same age and regular cycles) served as controls. Three girls had osteoporosis, with a BMD below -2 standard deviations (SD). Ten showed osteopenia, with a BMD value between -1 and -2 SD. Only six of the study group had a normal BMD within +/- 1 SD. A positive correlation was observed between the BMD and the BMI (r = 0.73; p < 0.05). All the controls had normal hormonal, ion and BMD parameters. 'Pure' dysfunction of the HPO axis in adolescents, causing oligomenorrhea or secondary amenorrhea, might result in reduced BMD and, consequently, lower peak bone mass. Treatment of menstrual cycle disorders is necessary for the prevention of osteoporosis.

Drugs acting on calcium channels modulate the diuretic and micturition effects of dexmedetomidine in rats.

The purpose of this study was to assess the effects of calcium channel antagonist, verapamil, and agonist, Bay K 8644, on the alpha 2-adrenoceptor agonist, dexmedetomidine-induced (300 micrograms kg-1 subcutaneously) diuresis and overflow incontinence, in rats. Ultrasonography study revealed that verapamil (2.5 mg kg-1 subcutaneously) or Bay K 8644 (0.5 mg kg-1 intraperitoneally) coadministrations delayed dexmedetomidine-induced bladder filling and significantly prolonged the latency of urination (P < 0.05). Bay K 8644 decreased relative bladder volume and stopped continuous urination from dexmedetomidine, whereas verapamil had neither effect. However, none of the drugs eliminated the overflow incontinence. Dexmedetomidine alone increased the hourly and total (for 4 hours) urine volume. Bay K 8644 (0.5 or 1 mg kg-1) dose-dependently decreased the diuretic effect of dexmedetomidine (P < 0.01). Verapamil (0.5, 1 or 2.5 mg kg-1) dose-dependently decreased urine volume in the first hour (P < 0.01), and thereafter potentiated the diuretic effect of dexmedetomidine. Simultaneous determinations of mean arterial blood pressure (MAP) and urine output after dexmedetomidine and the highest dose of verapamil coadministration demonstrated a significant correlation between these variables (r = 0.537; P < 0.001). MAP of 100 mmHg or less was associated with a urine output significantly lower (P < 0.001) than that at higher pressures. Thus, hypotension during the first hour after dexmedetomidine-verapamil may explain the transient reduction in urination during this period. We conclude that modulation of calcium channel affects dexmedetomidine actions on both urine formation and micturition. Since both alpha 2-adrenoceptor agonists and calcium channel blockers have frequently been used for antihypertensive therapy and as adjuvant drugs during anesthesia, these interactions may have some practical importance.

Structural basis for the extreme thermostability of D-glyceraldehyde-3-phosphate dehydrogenase from Thermotoga maritima: analysis based on homology modelling.

D-Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from a hyperthermophilic eubacterium, Thermotoga maritima, is remarkably heat stable (Tm = 109 degrees C). In this work, we have applied homology modelling to predict the 3-D structure of Th.maritima GAPDH to reveal the structural basis of thermostability. Three known GAPDH structures were used as reference proteins. First, the rough model of one subunit was constructed using the identified structurally conserved and variable regions of the reference proteins. The holoenzyme was assembled from four subunits and the NAD molecules. The structure was refined by energy minimization and molecular dynamics simulated annealing. No errors were detected in the refined model using the 3-D profile method. The model was compared with the structure of Bacillus stearothermophilus GAPDH to identify structural details underlying the increased thermostability. In all, 12 extra ion pairs per subunit were found at the protein surface. This seems to be the most important factor responsible for thermostability. Differences in the non-specific interactions, including hydration effects, were also found. Minor changes were detected in the secondary structure. The model predicts that a slight increase in alpha-helical propensities and helix-dipole interactions also contribute to increased stability, but to a lesser degree.