Studies on human uterine cervix and rat uterus using S-, X- and Q-band electron-spin-resonance spectroscopy.

In previous studies we have reported on the detection of a strong e.s.r. signal in samples of normal human cervix; the signal is much reduced or absent in samples of invasive cancer of the cervix. In order to identify the species responsible for the strong signal, we have used X-, S- and Q-band e.s.r. spectroscopy. The major signal that is detectable in ground-up samples of cervix preserved at -196 degrees C has features consistent with the presence of a peroxy free radical. Good agreement with the experimental findings was obtained by computer simulation, using values for the g-tensor of gx = 2.002, gy = 2.005 and gz = 2.036. The peroxy radical is produced on grinding the normal cervix samples to a powder under liquid N2, and appears to be formed by modification of a pre-existing oxygen-containing complex. Control experiments eliminated the possibility that the strong signals seen in frozen powders prepared from normal cervix were artefacts only of the grinding procedure. Experiments with rats in vivo and with cervix samples in vitro are consistent with the conclusion that the peroxy radical is formed by disturbing the cyclo-oxygenase system that is involved in prostaglandin synthesis.     

The value of decreasing the duration of the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection

Finding medications or vaccines that may decrease the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could potentially reduce transmission in the broader population. We developed a computational model of the U.S. simulating the spread of SARS-CoV-2 and the potential clinical and economic impact of reducing the infectious period duration. Simulation experiments found that reducing the average infectious period duration could avert a median of 442,852 [treating 25% of symptomatic cases, reducing by 0.5 days, reproductive number (R₀) 3.5, and starting treatment when 15% of the population has been exposed] to 44.4 million SARS-CoV-2 cases (treating 75% of all infected cases, reducing by 3.5 days, R₀ 2.0). With R₀ 2.5, reducing the average infectious period duration by 0.5 days for 25% of symptomatic cases averted 1.4 million cases and 99,398 hospitalizations; increasing to 75% of symptomatic cases averted 2.8 million cases. At $500/person, treating 25% of symptomatic cases saved $209.5 billion (societal perspective). Further reducing the average infectious period duration by 3.5 days averted 7.4 million cases (treating 25% of symptomatic cases). Expanding treatment to 75% of all infected cases, including asymptomatic infections (R₀ 2.5), averted 35.9 million cases and 4 million hospitalizations, saving $48.8 billion (societal perspective and starting treatment after 5% of the population has been exposed). Our study quantifies the potential effects of reducing the SARS-CoV-2 infectious period duration.     

Atrial natriuretic hormone secretion in patients with renal failure

To study the effects of volume overload and renal failure on plasma levels of immunoreactive atrial natriuretic hormone (IR-ANH), we measured levels of this hormone in normal subjects, in patients with advanced chronic renal failure (CRF) with and without clinically evident volume overload, and in patients with end-stage renal disease (ESRD) treated with chronic hemodialysis. The levels were 13 +/- 2 pmol/l in normal volunteers, 77 +/- 24 pmol/l in patients with CRF without volume overload, and 219 +/- 50 pmol/l in patients with CRF and clinically evident volume overload (analysis of variance, p less than 0.001, alpha = 0.05 compared to normals). In patients with ESRD, the levels of IR-ANH were 145 +/- 46 pmol/l before dialysis and decreased to 87 +/- 31 after dialysis (p less than 0.025). No correlation was found between the decrease in IR-ANH levels and the decrease in weight during dialysis. A significant positive correlation was found between the IR-ANH levels and blood urea nitrogen in patients with CRF (r = 0.658, p less than 0.01). Volume overload appears to be the most important stimulatory factor for ANH secretion in renal failure patients but other mechanisms, especially a decrease in metabolic clearance, may also contribute to elevated plasma levels. The increased secretion of ANH in patients with renal failure may be an important adaptive response to volume overload and hypertension.     

Pendular mechanics and the kinematics and energetics of brachiating locomotion

Because brachiating locomotion is characterized by a pattern of swinging movements, brachiation has often been analogized to pendular motion, and aspects of the mechanics of pendular systems have been used to provide insight into both energetic and structural design aspects of this locomotor mode. However, there are several limitations to this approach. First, the motions of brachiating animals only approximate pendular motion, and therefore the energetics of these two systems are only roughly comparable. Second, the kinematic similarity between brachiation and pendular motion will be maximal at only one velocity, and the correspondence will be even less at greater or lesser speeds. Third, all forms of terrestrial locomotion that involve the use of limbs incorporate elements of pendular systems, and therefore brachiation is not unusual in this respect. Finally, it has been suggested that the mechanics of pendular motion will constrain the maximum attainable body size of brachiating animals and that this mechanical situation explains the lack of brachiating primates of greater than 30-kg body size; the present analysis provides evidence that the constraints on body size are far less strict than previously indicated and that extrinsic factors such as the geometry of the forest environment are more likely to dictate maximum body size for brachiators.     

The critical relationship between free radicals and degrees of ischemia: evidence for tissue intolerance of marginal perfusion

Skin-flap ischemia has been associated with the presence of free radicals. In this study, two enzyme systems involved in free-radical metabolism were used to compare a distal skin flap to a skin graft. Forty-two rats were divided into several test groups. A 10 X 3 cm dorsal rat flap was used, and tissue biopsies for xanthine oxidase and malonyldialdehyde (MDA) were obtained 2.5, 5.5, and 8.5 cm from the base of the flap at the hours given. In group I (control), the flap was outlined but not elevated, and biopsies were obtained. In group II, the flap was elevated, and biopsies were obtained at 6 hours. In group III, the flap was elevated, the distal 4 X 3 cm was amputated and replaced as a full-thickness skin graft, and biopsies were obtained at 6 hours. In group IV, the flap was elevated, and biopsies were obtained at 12 hours. In group V, the flap was treated as in group III, and biopsies were obtained at 12 hours. In group VI, the flap was elevated, and biopsies were obtained at 24 hours. In group VII, the flap was treated as in group III, and biopsies were obtained at 24 hours. Results: Xanthine oxidase was significantly higher in all distal biopsies compared to proximal biopsies. Xanthine oxidase also increased with time. Malonyldialdehyde increased over time as well as with distance from the flap base. Distal flap biopsies at 24 hours had greatly increased levels of malonyldialdehyde compared to skin grafts (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Kinetics of enzyme-mediated reduction of lipid soluble nitroxide spin labels by living cells

Nitroxide spin labels can be reduced to the corresponding hydroxylamines in cells. The selective action of inhibitors, and thermal and chemical inactivation demonstrate that the reduction of nitroxides in cells is an enzymatic or enzyme-mediated process. The kinetics of reduction of doxylstearates are affected by the position of the doxyl moiety along the stearic acid chain. The doxyl moiety of 5-doxylstearate is close to the membrane surface, and its reduction is first order with respect to the nitroxide, whereas the doxyl moieties of 10- and 12-doxylstearate are in the membrane hydrocarbon region and their reduction is a zero-order process. The reduction of 16-doxylstearate which usually has a mixture of first- and zero-order kinetics becomes zero order with addition of an extracellular broadening agent, potassium trioxalatochromiate(III). These results suggest that the rate of reduction of doxyl moieties is controlled by their accessibility to reducing equivalents, i.e., the rate-limiting step for the reduction of the doxyl moiety deep in the membrane is the diffusion of reducing equivalents within or into the membrane. The reduction of doxylstearates in cells is inhibited by rotenone but not antimycin A, cyanide, propyl gallate or SKF-525A. It appears that the reduction of doxylstearates takes place at the level of the ubiquinone in the respiratory chain in mitochondria in these cells.     

Suppression of defective-sporulation phenotypes by mutations in the major sigma factor gene (rpoD) of Bacillus subtilis

Summary Mutations (crsA47 and crsA4) in the major sigma factor gene (rpoD) of Bacillus subtilis RNA polymerase have been found to be powerful intergenic suppressors of spoOB, spoOE, spoOF, spoOK and spoIIG mutations. The crsA47 suppressor restores sporulation of spoOE, spoOF, spoOK and spoIIG mutants to levels near those of wild type bacteria and substantially improves the sporulation of a spoOB strain. The crsA mutations are shown to prevent the induction by aliphatic alcohols of SpoO phenocopies in wild type B. subtilis cells.     

Adrenalectomy of Rats Results in Hypomyelination of the Central Nervous System

The effect of adrenalectomy on CNS myelin accumulation was investigated to determine whether glucocorticoids play a role in regulating myelination. When 14-day-old rats were adrenalectomized and sacrificed 7-8 days later, the amount of bulk-isolated myelin in whole brain, as expressed per gram wet weight of brain or per milligram DNA-phosphate, was reduced to about 75% that of sham-operated controls. Both brain weight and DNA content were unchanged by adrenalectomy. Examination of individual brain regions also revealed decreased amounts of myelin in adrenalectomized animals. Brain glycerol 3-phosphate dehydrogenase specific activity was reduced in adrenalectomized animals to 40-60% that of controls, and serum corticosterone levels were less than 0.6% of control levels. The amount of cerebral myelin in animals adrenalectomized on day 21 and sacrificed 9 days later was not significantly reduced. This suggests a possible role of glucocorticoids during the early period of rapid myelination.