The decomposition of azibenzil in the presence of oxygen

The ozonolysis of acetylenes is thought to proceed through the formation of ∝-carbonyl carbonyl oxide intermediates. This reaction has been shown to parallel the effect of molecular oxygen on ketocarbenes. Azibenzil, a diazo-ketone, will decompose to a ketocarbene by the action of heat, light or catalyst. The ketocarbene may decompose by two pathways: Wolff rearrangement and non-rearrangement. The Wolff rearrangement route will produce methyldiphenylacetate (upon addition of methanol), benzophenone, tetraphenylglycolide and possibly other high molecular weight polymeric species. The non-rearrangement pathway will presumably produce ∝-carbonyl carbonyl oxides which will decompose under varying circumstances to produce benzyl, benzoic anhydride, benzophenone, tetraphenylglycolide and other similar polymers. Evidence suggests that the thermal oxygenation of azibenzil proceeds principally via the rearrangement pathway; however, the production of triplet state ∝-carbonyl carbonyl oxides is indicated. The catalyzed reaction also undergoes rearrangement; however, due to the ability of the catalyst to promote intersystem crossing, singlet and triplet state acyl carbonyl oxides are formed. The singlet configuration of this species appears to be responsible for the formation of the benzoic anhydride and of some benzyl. The triplet state can decompose by an alternate method and generate benzophenone, tetraphenylglycolide, polymers and again some benzil

Development of Gradient Compression Garments for Protection Against Post Flight Orthostatic Intolerance

Orthostatic intolerance after space flight is still an issue for astronaut health. No in-flight countermeasure has been 100% effective to date. NASA currently uses an inflatable anti-gravity suit (AGS) during reentry, but this device is uncomfortable and loses effectiveness upon egress from the Shuttle. The Russian Space Agency currently uses a mechanical counter-pressure garment (Kentavr) that is difficult to adjust alone, and prolonged use may result in painful swelling at points where the garment is not continuous (feet, knees, and groin). To improve comfort, reduce upmass and stowage requirements, and control fabrication and maintenance costs, we have been evaluating a variety of gradient compression, mechanical counter-pressure garments, constructed from spandex and nylon, as a possible replacement for the current AGS. We have examined comfort and cardiovascular responses to knee-high garments in normovolemic subjects; thigh-high garments in hypovolemic subjects and in astronauts after space flight; and 1-piece, breast-high garments in hypovolemic subjects. These gradient compression garments provide 55 mmHg of compression over the ankle, decreasing linearly to ~35 mmHg at the knee. In thigh-high versions the compression continues to decrease to ~20 mmHg at the top of the leg, and for breast-high versions, to ~15 mmHg over the abdomen. Measures of efficacy include increased tilt survival time, elevated blood pressure and stroke volume, and lower heart-rate response to orthostatic stress. Results from these studies indicate that the greater the magnitude of compression and the greater the area of coverage, the more effective the compression garment becomes. Therefore, we are currently testing a 3-piece breast-high compression garment on astronauts after short-duration flight. We chose a 3-piece garment consisting of thigh-high stockings and shorts, because it is easy to don and comfortable to wear, and should provide the same level of protection as the 1-piece breast-high garments evaluated in hypovolemic test subjects

Custom Gradient Compression Stockings May Prevent Orthostatic Intolerance in Astronauts After Space Flight

Orthostatic intolerance after space flight is still an issue for astronauts as no in-flight countermeasure has been 100% effective. NASA astronauts currently wear an inflatable anti-gravity suit (AGS) during re-entry, but this device is uncomfortable and loses effectiveness upon egress from the Shuttle. We recently determined that thigh-high, gradient compression stockings were comfortable and effective after space flight, though to a lesser degree than the AGS. We also recently showed that addition of splanchnic compression to this thigh-high compression stocking paradigm improved orthostatic tolerance to a level similar to the AGS, in a ground based model. Purpose: The purpose of this study was to evaluate a new, three-piece breast-high gradient compression garment as a countermeasure to post-space flight orthostatic intolerance. Methods: Eight U.S. astronauts have volunteered for this experiment and were individually fitted for a three-piece, breast-high compression garment to provide 55 mmHg compression at the ankle which decreased to approximately 20 mmHg at the top of the leg and provides ~15 mmHg over the abdomen. Orthostatic testing occurred 30 days pre-flight (w/o garment) and ~2 hours after flight (w/ garment) on landing day. Blood pressure (BP), Heart Rate (HR) and Stroke Volume (SV) were acquired for 2 minutes while the subject lay prone and then for 3.5 minutes after the subject stands up. To date, two astronauts have completed pre- and post-space flight testing. Data are mean SD. Results: BP [pre (prone to stand): 137+/-1.6 to 129+/-2.5; post: 130+/-2.4 to 122+/-1.6 mmHg] and SV [pre (prone to stand): 61+/-1.6 to 38+/-0.2; post: 58+/-6.4 to 37+/-6.0 ml] decreased with standing, but no differences were seen post-flight w/ compression garments compared to pre-flight w/o garments. HR [pre (prone to stand): 66+/-1.6 to 74+/-3.0, post: 67+/-5.6 to 78+/-6.8 bpm] increased with standing, but no differences were seen pre- to post-flight. Conclusion: After space flight, blood pressure and stroke volume are normally decreased and heart rate is usually elevated to compensate. In this small group of subjects, breast-high gradient compression stockings seem to have prevented these negative effects of spaceflight

NIRS-Derived Tissue Oxygen Saturation and Hydrogen Ion Concentration Following Bed Rest

Long-term bed rest (BR), a model of spaceflight, results in a decrease in aerobic capacity and altered submaximal exercise responses. The strongest BR-induced effects on exercise appear to be centrally-mediated, but longer BR durations may result in peripheral adaptations (e.g., decreased mitochondrial and capillary density) which are likely to influence exercise responses. PURPOSE: To measure tissue oxygen saturation (SO2) and hydrogen ion concentration ([H+]) in the vastus lateralis (VL) using near infrared spectroscopy (NIRS) during cycle ergometry before and after . 30 d of BR. METHODS: Eight subjects performed a graded exercise test on a cycle ergometer to volitional fatigue 7 d before (pre-BR) and at the end or 1 day after BR (post-BR). NIRS spectra were collected from a sensor adhered to the skin overlying the VL. Oxygen consumption (VO2) was measured by open circuit spirometry. Blood volume (BV) was measured before and after BR using the carbon monoxide rebreathing technique. Changes in pre- and post-BR SO2 and [H+] data were compared using mixed model analyses. BV and peak exercise data were compared using paired t-tests. RESULTS: BV (pre-BR: 4.3+/-0.3, post-BR: 3.7+/-0.2 L, mean+/-SE, p=.01) and peak VO2 (pre-BR: 1.98+/-0.24, post-BR: 1.48 +/-0.21 L/min, p<.01) were reduced after BR. As expected, SO2 decreased with exercise before and after BR. However, SO2 was lower post compared with pre-BR throughout exercise, including at peak exercise (pre-BR: 50+/-3, post-BR: 43+/-4%, p=.01). After BR, [H+] was higher at the start of exercise and did not increase at the same rate as pre-BR. Peak [H+] was not different from pre to post-BR (pre-BR: 36+/-2; post-BR: 38+/-2 nmol/L). CONCLUSIONS: Lower SO2 during exercise suggests that oxygen extraction in the VL is higher after BR, perhaps due to lower circulating blood volume. The higher [H+] after BR suggests a greater reliance upon glycolysis during submaximal exercise, although [H+] at peak exercise was unchanged. Taken together, these data suggest that longer duration BR induces a number of changes that result in peripheral adaptations which contribute to cardiovascular and muscular deconditioning as measured by NIRS-derived SO2 and [H+] in the VL and may contribute to lower post-BR exercise tolerance. Supported by the National Space Biomedical Research Institute through NASA NCC 9-5

Gradient Compression Stockings may Prevent Recovery after Bed Rest Deconditioning

Introduction: Astronauts continue to wear a compression garment during and immediately after landing to prevent orthostatic intolerance (OI). We recently developed a custom-fitted, 3-piece garment that consists of thigh-high stockings with biker-style shorts that provides continuous, gradient compression: 55 mmHg at the ankle that decreases to approximately 20 mmHg at the top of the leg and 15 mmHg over the abdomen. This garment has been shown to be effective in preventing symptoms of OI during a short stand test after Space Shuttle missions, but symptoms may persist for several days after a long-duration mission in some astronauts. The purpose of this study was to confirm the effectiveness of wearing these elastic, gradient compression garments during orthostatic testing after 2 weeks of 6 degree head-down tilt bed rest as a model of spaceflight and to determine whether they would impact recovery after bed rest. Methods: Eight (5 treatment, 3 control) of 16 subjects have completed this study to-date. All subjects wore the 3-piece garment from waking until tilt testing (~3 h) as a simulation of the timeline for astronauts on landing day (BR+0). Control subjects removed the garment after the tilt test. Treatment subjects wore the garment for the remainder of the day and wore lower compression thigh-high only garments on the day after bed rest (BR+1). Blood pressure, heart rate, and stroke volume responses to a 15-min 80 degree head-up tilt test were determined before 2 weeks of 6 degree head-down tilt, and on BR+0 and BR+1. Plasma volume (PV) was measured before each of these test sessions. Data are mean SE. Results: Compression garments prevented signs of OI on BR+0; all subjects in both groups completed the full 15-min test. Heart rate responses to tilt were lower on BR+0 than all other test days. Control subjects demonstrated a marginal PV decrease after bed rest, but showed typical recovery the day after bed rest (BR+0: 2.32 plus or minus 0.15 L to BR+1: 2.79 plus or minus 0.15 L). Treatment subjects did not recover PV the day after bed rest (BR+0: 2.61 plus or minus 0.23 L to BR+1: 2.61 plus or minus 0.23 L). Conclusion: Abdomen-high compression garments, which are effective in preventing post-bed rest orthostatic intolerance, may slow recovery of PV. Modified garments with reduced compression may be necessary to prevent prolonging recovery

Circadian deep sequencing reveals stress-response genes that adopt robust rhythmic expression during aging

Disruption of the circadian clock, which directs rhythmic expression of numerous output genes, accelerates aging. To enquire how the circadian system protects aging organisms, here we compare circadian transcriptomes in heads of young and old Drosophila melanogaster. The core clock and most output genes remained robustly rhythmic in old flies, while others lost rhythmicity with age, resulting in constitutive over- or under-expression. Unexpectedly, we identify a subset of genes that adopted increased or de novo rhythmicity during aging, enriched for stress-response functions. These genes, termed late-life cyclers, were also rhythmically induced in young flies by constant exposure to exogenous oxidative stress, and this upregulation is CLOCK-dependent. We also identify age-onset rhythmicity in several putative primary piRNA transcripts overlapping antisense transposons. Our results suggest that, as organisms age, the circadian system shifts greater regulatory priority to the mitigation of accumulating cellular stress

Alternative Compression Garments

Orthostatic intolerance after spaceflight is still an issue for astronauts as no in-flight countermeasure has been 100% effective. Future anti-gravity suits (AGS) may be similar to the Shuttle era inflatable AGS or may be a mechanical compression device like the Russian Kentavr. We have evaluated the above garments as well as elastic, gradient compression garments of varying magnitude and determined that breast-high elastic compression garments may be a suitable replacement to the current AGS. This new garment should be more comfortable than the AGS, easy to don and doff, and as effective a countermeasure to orthostatic intolerance. Furthermore, these new compression garments could be worn for several days after space flight as necessary if symptoms persisted. We conducted two studies to evaluate elastic, gradient compression garments. The purpose of these studies was to evaluate the comfort and efficacy of an alternative compression garment (ACG) immediately after actual space flight and 6 degree head-down tilt bed rest as a model of space flight, and to determine if they would impact recovery if worn for up to three days after bed rest