Indometh acin-antihistamine combination for gastric ulceration control

An anti-inflammatory and analgesic composition containing indomethacin and an H2 histamine receptor antagonist in an amount sufficient to reduce gastric distress caused by the indomethacin was developed. Usable antagonists are metiamide and cimetidine

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

Hormonal regulation of fluid and electrolyte metabolism in zero-g and bedrest

The study of man in spaceflight has consistently indicated changes in fluid and electrolyte balance. Sodium (Na), Potassium (K), and Calcium (Ca) excretion are increased, accompanied by changes in the levels and responsiveness of adrenal hormones and the sympathetic nervous system (SNS). These hormones and neurohumors are critical to the regulation of blood pressure, blood flow, and blood volume. The primary objectives of the research conducted under this task have been to use -6 deg head down bedrest (BR) as the analog to spaceflight, to determine the long term changes in these systems, their relationship to orthostatic tolerance, and to develop and test suitable countermeasures

Realising offsite construction in the civil engineering and infrastructure sector

Offsite construction solutions have gained significant prominence over recent years. Much of the interest however, has been focussed on the building sector, in particular housing. The Civil Engineering and Infrastructure sector (CE&I) has comparatively seen little growth in this aspect. Specific exemplars for some high-profile projects, such as the Heathrow Airport control tower, do exist, but there have been far less applications of the new and emerging technologies and approaches that have been influential in the building sector recently. In addition, Offsite itself is not a well-defined supply sector, but rather a conglomeration of various, largely material or technology-based supply networks. This makes it difficult to realise new opportunities, especially in different sectors of the construction industry. This thesis is the culmination of a four-year Engineering Doctorate (EngD) research programme investigating the components that affect the realisation of offsite in the CE&I sector. It commences with an introduction to the research and its aims and objectives, and moves on to present the methodological considerations. During the four Work Packages (WP) conducted, a total of 78 individuals participated and contributed to workshop and interviews, together with an extensive critical review of literature. All primary and secondary data was examined with appropriate methods, such as a comparative case study and an emergent thematic analysis, upon which a series of conclusions and subsequently recommendations were drawn. The findings clearly identify that CE&I is more risk averse, and defines offsite differently, to the building sector. Each CE&I sub-sector has specific drivers and barriers to offsite, and due to the relative longevity of CE&I projects (both procurement, design, and construction) makes it difficult to benchmark and quantify offsite and its benefits. Large programmes of works rather than small projects are key to realising offsite as they provide confidence to the supply chain of long term investment. In addition, clients are pivotal for driving offsite as they can influence the industry s focus; nevertheless, investment cycles in infrastructure clients hinders offsite realisation. For holistic offsite implementation organisation need to have a top-down strategy. Therefore offsite requirements should be embedded within the project delivery governance processes. Its realisation is linked directly to recruitment, training and research and development plans. Building information modelling (BIM) now plays a key part in offsite realisation in CE&I as from 2016 it will be compulsory for all centrally-funded government works. BIM however, does not directly increase the offsite implementation, but it can help enable offsite due to the ability to define the design earlier in the project lifecycle. In addition, BIM encourages the use of software that can help identify the repetition of components, therefore increasing the potential for economies to scale. Finally, with the use of such software, delivery teams can simulate the construction sequence and therefore further help to enable offsite by reducing logistical challenges

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

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

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

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

Continuous exposure to gravity may not be necessary to prevent the deconditioning effects of microgravity. It is not known, however, what the minimum gravity (G) exposure reguirements are, whether they vary for different physiological systems, or whether passive Gz (gravity in the head-to-toe vector) or activity in a G field is more effective in preventing deconditioning. It is also not known what the optimal characteristics of the G stimulus should be in terms of amplitude, duration, and frequency. To begin to address these questions, a 4-day -6 deg head-down bed rest (HDBR) study was conducted. Nine males (aged 30-50 yr) were subjected, over a period of seven months, to four different +1 Gz exposure protocols (periodic standing or controlled walking each for a total of 2 or 4 hr/day in individual 15-min doses), plus a control (0 Gz) of continuous HDBR. The study consisted of one ambulatory control day, 4 full days of -6 deg HDBR, and a recovery day when subjects were released at the end of HDBR after completion of tests. A battery of tests was selected and standardized in order to evaluate the known early responses to HDBR. Dependent variables of interest included orthostatic tolerance (30 min at 60 deg head-up tilt) and hemodynamics during head-up tilt, peak oxygen consumption (VO2(sub peak)) plasma volume (PV), and urinary calcium (Ca). The results were as follows: 4 hr standing completely prevented and 2 hr walking partially prevented post-HDBR orthostatic intolerance. Walking at 3 mi/hr for 4 hr/day provided no additional benefit. Intermittent walking attenuated, but did not prevent, the decrease in VO2(sub peak). Both 4 hr conditions showed less PV loss by the end of HDBR; both 2 hr conditions were without effect. Both 2 and 4 hr walking essentially prevented urinary Ca excretion and were more effective than standing. It is concluded that different physiological systems benefit differentially from passive +1 Gz or activity in +1 Gz, and the intensity of the stimulus may be an important contributing factor

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