Michael E. Soulsby

The Antiseptic Efficacy of Chlorxylenol-Containing vs. Chlorhexidine Gluconate-Containing Surgical Scrub Preparations

The studies described here evaluate the efficacy of the chlorxylenol-containing surgical scrub formulations against the chlorhexidine gluconate-containing formulations using the Glove Juice Test, as recommended by the FDAs panel to develop guidelines for the study of antiseptic agents. Similar reports from the literature evaluating the relative efficacies of the iodophor-containing and the hexachlorophene-containing formulations are cited. Results fail to detect any significant differences in the efficacy of these two preparations, each significantly reducing the bacterial flora on the hands as indicated by immediate post-wash colony counts, and each demonstrating the continuing ability to significantly reduce bacterial growth with continued regular use.

Pressure Hyperalgesia in Hind Limb Suspended Rats

INTRODUCTION Spaceflight and simulated microgravity often associate with pain and prediabetes. Streptozotocin (STZ)-induced moderate insulinopenia rat models of prediabetes result in pressure hyperalgesia. The current study was designed to determine whether or not simulated microgravity induced by hind limb suspension (HLS) in rats lead to insulinopenia and pressure hyperalgesia. METHODS Adult male rats were divided into HLS (N = 20) and control, non-suspended (N = 16) groups, respectively. Bodyweight and hind limb pressure-pain withdrawal threshold (PPT) were measured at regular 2-5 d intervals for 7 d before and 12-13 d after HLS. RESULTS Bodyweights and PPT of control and HLS animals measured on the day of suspension were not different. During the experiment, control rats gained 61 +/- 5 g, but maintained their PPT at the baseline level. Suspended rats gained 26 +/- 3 g of weight during the same time period and their PPT declined from 105 +/- 6 g to 84 +/- 6 g. Neither blood glucose nor pancreatic islet density and area were affected by HLS. However, the random plasma insulin of HLS rats was significantly lower than that of control animals (1.6 +/- 0.2 vs. 2.7 +/- 0.2 ng ml(-1)). DISCUSSION The observed relationship between insulin and PPT levels in the HLS rats was similar to that observed in rats with STZ-induced insulinopenia. These data suggest that moderate insulinopenia may affect the rats sensitivity to deep pressure directly, without affecting glucose homeostasis. In addition, our data suggest that HLS rats may develop peripheral neuropathy.

Oxidant/Anti-Oxidant Status in Rats Exposed to Simulated Weightlessness by Hind-Limb Unloading and Reloading

Hindlimb suspension or better known as hind-limb unloading (HLU) of rats is a validated model representing weightlessness, simulating microgravity. This is accomplished by removal of weight-bearing loads from hindquarters pro- ducing a cephalic fluid shift. The current study examines whether exposure to microgravity by hind-limb unloading will activate oxidant/antioxidant defense system. Tissue levels of malondialdehyde (MDA), total glutathione (GSH+GS-SG) and superoxide dismutase (SOD) were measured in harvested tissues following HLU and reloading. To rule out any vari- ability in normal dietary oxidant intake, all animals received in their diet Purina rat chow containing 9.6% soy meal (4.8% soy protein). Results show that tissues harvested from rats following 2 weeks of unloading had significantly elevated MDA levels ranging from 0.3 - 0.8� M/mg protein when compared to paired loaded controls (0.2 - 0.4μM/mg protein, p < 0.5). Tissues from rats reloaded for 2 weeks following unloading decreased MDA levels from their peak values (p<0.05). GSH levels increased up to 350 � M depending on tissues as a result of unloading, and two weeks of reloading decreased GSH levels to 250 � M from their peak levels. SOD levels increased in all harvested organs in unloaded group ranging from 0.8 - 4.0� M with continued increase after two weeks of reloading, p < 0.05). Our data indicate that oxidative stress is induced during unloading as evidenced by increased tissue MDA levels. The response involves an increase in GSH and SOD levels, but two weeks of reloading decreased MDA and GSH levels, while further increasing SOD levels, implying the tissue adaptation to induced oxidative stress.

Animal model of simulated microgravity: a comparative study of hindlimb unloading via tail versus pelvic suspension

The aim of this study was to compare physiological effects of hindlimb suspension (HLS) in tail‐ and pelvic‐HLS rat models to determine if severe stretch in the tail‐HLS rats lumbosacral skeleton may contribute to the changes traditionally attributed to simulated microgravity and musculoskeletal disuse in the tail‐HLS model. Adult male Sprague‐Dawley rats divided into suspended and control‐nonsuspended groups were subjected to two separate methods of suspension and maintained with regular food and water for 2 weeks. Body weights, food and water consumption, soleus muscle weight, tibial bone mineral density, random plasma insulin, and hindlimb pain on pressure threshold (PPT) were measured. X‐ray analysis demonstrated severe lordosis in tail‐ but not pelvic‐HLS animals. However, growth retardation, food consumption, and soleus muscle weight and tibial bone density (decreased relative to control) did not differ between two HLS models. Furthermore, HLS rats developed similar levels of insulinopenia and mechanical hyperalgesia (decreased PPT) in both tail‐ and pelvic‐HLS groups. In the rat‐to‐rat comparisons, the growth retardation and the decreased PPT observed in HLS‐rats was most associated with insulinopenia. In conclusion, these data suggest that HLS results in mild prediabetic state with some signs of pressure hyperalgesia, but lumbosacral skeleton stretch plays little role, if any, in these pathological changes.

Studies of Hard and Soft Tissue Elemental Compositions in Mice and Rats Subjected to Simulated Microgravity

Microgravity has profound effects on skeletal as well as other body systems. To investigate the effect of microgravity, we have used a NASA validated Hind‐limb suspension (HLS) animal model of simulated weightlessness. Groups of mice and rats were subjected to hind limb suspension between 1 and 14 days while the control groups were maintained without suspension for the same duration. To study the effect of diet, some groups of animals were fed on a special diet with defined composition. At term, the animals were sacrificed and the tibia, femur, and skull bones were collected. In addition, soft tissues from pancreas and muscles were also collected. All of the bones and tissues samples were analyzed for elemental analysis using Energy Dispersive Spectroscopy (EDS) equipped on a Scanning Electron Microscope (SEM). In the EDS, 10–20 keV electrons bombarded the samples and a Si (Li) detector measured K‐, L‐ and M‐shell x‐rays. Independently, X‐Ray Fluorescence (XRF) provided the data for comparison and normalization. Flame software, with Fuzzy Logic, was used to form elemental ratios. Elemental analysis of bone samples indicated a variation in the compositional ratios of calcium, potassium, oxygen and carbon in the leg bones and skulls of the HLS versus control specimens. These variations showed dependence on sample position in the bone.

Vessel dilator is associated with survival after acute myocardial infarction

To assess whether infarct size, ischemic area and/or survival correlates with circulating atrial natriuretic peptides (long acting sodium stimulator, vessel dilator, or atrial natriuretic factor), these peptides were measured in a canine model of acute myocardial infarction. Elevations in the circulating concentrations of atrial natriuretic factor, vessel dilator, and long acting sodium stimulator were significant (P < 0.05) within 6 min of coronary occlusion of the left anterior descending coronary artery. The percentage of ischemic myocardium ranged from 20 to 67% with a mean of 37 +/- 17%. The area of infarction ranged from 1 to 13% with the infarcted area of non-survivors being twice that of survivors. Both the ischemic and infarcted areas correlated (P < 0.05) with the circulating concentrations of these atrial natriuretic peptides. Survival correlated also with the circulating plasma concentrations of vessel dilator, atrial natriuretic factor and long acting sodium stimulator (P < 0.05). When these circulating concentrations were evaluated, however, by determining their area under their respective concentrations curves and expressing each as the log area under plasma concentration-time curve (area under the curve) per kg of weight (Y = 58.48X-23.62; r = 0.825; P = 0.0009), vessel dilator was the only atrial natriuretic peptide that correlated with survival.

Effects of Dietary Soy Protein on Hematological and Tissue Oxidant/Anti- Oxidant Levels in Rats Exposed to Simulated Microgravity

Effects of a soy protein diet on oxidant and anti-oxidant levels in selected rodent tissues were investigated under simulated microgravity. Methods: Adult Male Rats were maintained either on a regular Purina Rat chow or on a 9.6% soy protein diet and allowed to remain in either non-suspended (control) or hind-limb-suspended (HLS) state via their tails at a 30 degree angle for 14 days. Body weights, food and water intakes were monitored daily during the entire study period. Hematological parameters, oxidant and. antioxidant levels in the brain, liver and pancreatic tissues were measured. Results: At term, the body weights of the hind limb suspended animals were found significantly decreased when compared with the non-suspended controls, p<0.05. There was no significant change in blood hematocrit and hemoglobin levels. After HLS, malondialdehyde (MDA) levels of brain tissues were marginally increased in the Purina chow group as compared to a significant increase in the soy suspended group (p<0.05). Similar observations were noted with liver and pancreatic tissues. In response to HLS, glutathione levels in brain and pancreatic tissues were increased in the Purina chow group (p<0.05) while in soy group, glutathione (GT) levels in both of these tissues were found relatively lower. Superoxide dismutase (SOD) levels were increased in all three tissues after HLS regardless of the dietary conditions. Conclusions: Data suggest that HLS induced a differential tissue specific oxidative response regardless of the dietary differences. Dietary soy protein lowered the oxidant levels under basal state but their effects were not sustained under HLS conditions significantly.

Young's modulus and SEM analysis of leg bones exposed to simulated microgravity by hind limb suspension (HLS)

The aim of this study was to determine composition of the leg bone tissue of rats that were exposed to simulated microgravity by Hind-Limb Suspension (HLS) by tail for one week. The leg bones were cross sectioned, cleaned of soft tissues, dried and sputter coated, and then placed horizontally on the stage of a Scanning Electron Microscope (SEM) for analysis. Interaction of a 17.5 keV electron beam, incident from the vertical direction on the sample, generated images using two detectors. X-rays emitted from the sample during electron bombardment were measured with an Energy Dispersive Spectroscopy (EDS) feature of SEM using a liquid-nitrogen cooled Si(Li) detector with a resolution of 144 eV at 5.9 keV (25Mn Kα x-ray). Kα- x-rays from carbon, oxygen, phosphorus and calcium formed the major peaks in the spectrum. Relative percentages of these elements were determined using a software that could also correct for ZAF factors namely Z(atomic number), A(X-ray absorption) and F(characteristic fluorescence). The ...

PANCREATIC HISTOLOGY AND ASSOCIATED BIOCHEMICAL CHANGES IN RATS ON HIND‐LIMB SUSPENSION

The pancreas plays an important role in regulating many of the key endocrine hormones and digestive enzymes that are required for nutrition and survival of the organism. This study examines the pancreatic histology and associated biochemical changes in rats on hind limb suspension (HLS) after exposure to simulated microgravity. Results show that MDA and glutathione levels were significantly increased in the suspended (HLS) groups as compared to the control group. Plasma insulin levels averaged 2.43±0.32 ng/ml in the control animals and decreased significantly to 1.47±0.24 ng/ml in the suspended group. Histopathology revealed increased vacuolation, pyknosis, membrane thickening, increase of zymogen granules and increase in islets (both in size and number) in the suspended group as compared to the control group.

ANALYSIS OF 20 KEV ELECTRON INDUCED X‐RAY PRODUCTION IN SKULL, FEMUR/TIBIA BONES OF RATS

Hind‐limb suspension (HLS) of rats is a NASA validated model of simulated weightlessness. This study examines the effects of microgravity on the skeletal system of rats to assess whether or not exposure of rats to HLS for one week will induce alteration of structural features in selected bones. Four groups of rats were used: two unsuspended controls and two suspended groups. Body weight, food, and water intake were monitored daily before and after suspension. X‐rays were measured by a liquid nitrogen cooled Si(li) detector on a Scanning Electron Microscope (SEM) that provided the 20 keV electron beam. X‐ray data were collected from square cross sections between 100 μm2 and 104 μm2. The bones were measured for elemental levels of calcium, phosphorus, oxygen and carbon from both control and HLS rats. The average body weight of all HLS groups decreased compared to their respective unsuspended controls. Food and water intake was also lower in both suspended groups. A correlation among HLS and control samples ...