Naloxone inhibits and morphine potentiates. The adrenal steroidogenic response to ACTH

The adrenal actions were stereospecific since neither the positve stereoisomer of morphine, nor that of naloxone, had any effect on the adrenal response to exogenous adrenocorticotrophic hormone (ACTH). The administration of human beta endorphin to phyophysectomized rats had no effect on the adrenal corticosterone concentration nor did it alter the response of the adrenal gland to ACTH. These results indicate that morphine can potentiate the action of ACTH on the adrenal by a direct, stereospecific, dose dependent mechanism that is prevented by naloxone pretreatment and which may involve competition for ACTH receptors on the corticosterone secreting cells of the adrenal cortex

Stress antagonizes morphine-induced analgesia in rats

Exposure to restraint stress resulted in antagonism of the analgesic effect of administered morphine in adult male rats. This antagonism of morphine-induced analgesia by restraint stress was not affected by adrenalectomy one day prior to testing, suggesting that stress-induced secretion of corticosteroids is not critical to this antagonism. In addition, parenteral administration of exogenous adrenocorticotropin (ACTH) mimicked the effect of stress in antagonizing morphine's analgesic efficacy. The hypothesis that ACTH is an endogenous opiate antagonist involved in modulating pain sensitivity is supported

Artificial gravity: How much, how often, how long?

The argument is not overwhelming for the need to provide a continuous 1G environment using tethers or other means of spinning a spacecraft in order to maintain crew health in planetary exploration. Even on Earth, we spend a maximum of 16 hours in 1G (upright). Sporadic evidence over the years has suggested that somewhere between 30-minutes and 4-hours of 1G may suffice to prevent the deconditioning effects of bedrest (orthostatic intolerance and the rise in calcium excretion). However, it is not known what the minimum requirements are, whether they vary for different physiological systems and whether passive zero gravity or the enhancement of the effects of activity conducted in an increased G field are more effective. It is similarly not known what the optimal duration and frequency of the G stimulus is, and how time of day might alter its effectiveness. Since acceleration level and duration appear to be physiologically interactive, it seems feasible to hypothesize that periodic acceleration exposures to greater than 1G levels provided by some on-board centrifuge, would suffice and should be explored

ACTH-like peptides increase pain sensitivity and antagonize opiate analgesia

The role of the pituitary and of ACTH in pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 C. Hypophysectomy reduced pain sensitivity, and this effect was reversed by the intracerebroventricular (ICV) injection of the opiate antagonist naloxone. Similarly, the analgesia produced by a dose of morphine was antagonized by the administration of ACTH or alpha-MSH. The peripheral injection of ACTH or alpha-MSH in normal rats did not increase pain sensitivity. However, ACTH administered ICV increased pain sensivity within 10 min. The results indicate that the pituitary is the source of an endogenous opiate antagonist and hyperalgesic factor and that this factor is ACTH or an ACTH-like peptide. This activity resides in the N-terminal portion of the ACTH molecule since ACTH sub 4-10 is not active in this respect, nor does this activity require a free N-terminal serine since alpha-MSH appears to be almost as potent as the ACTH sub 1-24 peptide. It is concluded that ACTH-like peptides of pituitary origin act as endogenous hyperalgesic and opiate antagonistic factors

Endocrine and fluid metabolism in males and females of different ages after bedrest, acceleration and lower body negative pressure

Space shuttle flight simulations were conducted to determine the effects of weightlessness, lower body negative pressure (LBNP), and acceleration of fluid and electrolyte excretion and the hormones that control it. Measurements were made on male and female subjects of different ages before and after bedrest. After admission to a controlled environment, groups of 6 to 14 subjects in the age ranges 25 to 35, 35 to 45, 45 to 55 to 65 years were exposed to +3 G sub z for 15 minutes (G1) and to LBNP (LBNP1) on different days. On 3 days during this prebedrest period, no tests were conducted. Six days of bedrest followed, and the G sub z (G2) and LBNP (LBNP2) tests were run again. Hormones, electrolytes, and other parameters were measured in 24-hour urine pools throughout the experiment. During bedrest, cortisol and aldosterone excretion increased. Urine volume decreased, and specific gravity and osmolality increased. Urinary electrolytes were statistically unchanged from levels during the non-stress control period. During G2, cortisol increased significantly over its control and bedrest levels. Urine volume, sodium, and chloride were significantly lower; specific gravity and osmolality were higher during the control period or bedrest. The retention of fluids and electrolytes after +G sub z may at least partially explain decreased urine volume and increased osmolality observed during bedrest in this study. There were some who indicated that space flight would not affect the fluid and electrolyte metabolism of females or older males any more severely than it has affected that of male astronauts

Circadian, endocrine, and metabolic effects of prolonged bedrest: Two 56-day bedrest studies

Two bedrest studies of 56 days each have been conducted to evaluate the effects of prolonged bedrest on circadian synchrony and endocrine and metabolic function. Measurements included the pituitary-adrenal, thyroid, parathyroid, insulin-glucose-growth hormones, catecholamine excretion, body temperature, and heart rate. The results indicated that a rigorous regimen of exercise did not prevent the endocrine and metabolic effects of prolonged bedrest. Changes in circadian, endocrine, and metabolic functions in bedrest appear to be due to changes in hydrostatic pressure and lack of postural cues rather than to inactivity, confinement, or the bleeding schedule. Prolonged bedrest, particularly beyond 24 days, resulted in rhythm desynchronization in spite of well regulated light/dark cycles, temperature, humidity, activity, and meal times and meal composition and in increased lability of all endocrine parameter measured. It also resulted in an apparent insensitivity of the glucose response to insulin, of cortisol secretion to ACTH, and of growth hormone secretion to hypoglycemia

Periodic upright posture negates the suppression of neuroendocrine response to head down bedrest

Head down bedrest (HDT) decreases plasma neurohormone levels, attaining a nadir within four hours. The present study evaluates the effect of periodic standing or exercises (+G(z)) on this acute suppression of plasma neurohormones. Methods: Nine male subjects (mean plus or minus SE age 37 plus or minus 2 yr; height 182 plus or minus 2 cm; weight 83 plus or minus 3 kg) were admitted to the Human Research Facility on three occasions separated by one month. Subjects were assigned to head down tilt (minus 6 degrees) or 15-minutes of standing or moderate exercise at the end of each hour. Initially during an ambulatory period, subjects were placed in a supine position for 45-min and a control blood sample obtained. The next day following 4 hours of HDT with or without standing or exercise a blood sample was taken 45-min (3 3/4 hours into HDT) after the preceding stand or exercise. Blood was withdrawn and all plasma samples frozen for determination of neurohormone levels within the same assay. Plasma aldosterone, Plasma Renin Activity (PRA) vasopressin (AVP) and cortisol levels were measured by radioimmunoassay. Norepinephrine (NE) and epinephrine (E) levels were measured by electrochemical detection following HPLC. Values were compared by ANOVA, P less than 0.05. Results: Control levels following 45-min supine were not different between treatments. HDT suppressed plasma aldosterone (13.9 plus or minus 3.7 to 6.6 plus or minus 0.7 ng/dl) and NE levels (299 plus or minus 35 to 217 plus or minus 23 pg/dl), E (69 plus or minus 15 to 65 plus or minus 21 pg/ml), and PRA (0.64 plus or minus 0.13 to 0.58 plus or minus 0.17 ngAl/m/hr) were not significantly altered. Standing or exercise negated the decrease in aldosterone and NE levels due to HDT. Conclusions: Periodic upright posture (+G(z)) with or without exercise for 15-min out of each hour negates the acute suppression of aldosterone and NE associated with HDT

GeneViTo: Visualizing gene-product functional and structural features in genomic datasets

BACKGROUND: The availability of increasing amounts of sequence data from completely sequenced genomes boosts the development of new computational methods for automated genome annotation and comparative genomics. Therefore, there is a need for tools that facilitate the visualization of raw data and results produced by bioinformatics analysis, providing new means for interactive genome exploration. Visual inspection can be used as a basis to assess the quality of various analysis algorithms and to aid in-depth genomic studies. RESULTS: GeneViTo is a JAVA-based computer application that serves as a workbench for genome-wide analysis through visual interaction. The application deals with various experimental information concerning both DNA and protein sequences (derived from public sequence databases or proprietary data sources) and meta-data obtained by various prediction algorithms, classification schemes or user-defined features. Interaction with a Graphical User Interface (GUI) allows easy extraction of genomic and proteomic data referring to the sequence itself, sequence features, or general structural and functional features. Emphasis is laid on the potential comparison between annotation and prediction data in order to offer a supplement to the provided information, especially in cases of "poor" annotation, or an evaluation of available predictions. Moreover, desired information can be output in high quality JPEG image files for further elaboration and scientific use. A compilation of properly formatted GeneViTo input data for demonstration is available to interested readers for two completely sequenced prokaryotes, Chlamydia trachomatis and Methanococcus jannaschii. CONCLUSIONS: GeneViTo offers an inspectional view of genomic functional elements, concerning data stemming both from database annotation and analysis tools for an overall analysis of existing genomes. The application is compatible with Linux or Windows ME-2000-XP operating systems, provided that the appropriate Java Runtime Environment is already installed in the system