Preventive effect of rosiglitazone on liver injury in a mouse model of decompression sickness.

BACKGROUND AND AIMS: Severe decompression sickness (DCS) is a multi-organ injury. This study investigated the preventive effects of rosiglitazone on liver injury following rapid decompression in mice and examined the underlying mechanisms. METHODS: Mice were randomly divided into four groups: a control group, vehicle group, and rosiglitazone (5 and 10 mg·kg⁻¹) groups, the latter three being exposed to a pressure of 911 kPa. Haematoxylin and eosin staining, plasma levels of alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase and blood cell counts were used to evaluate liver injury at 30 min after rapid decompression. The expression of endothelial and inducible nitric oxide synthase (iNOS) and its phosphorylation were measured to uncover the underlying molecular mechanisms. RESULTS: A significant increase in plasma ALT, red blood cells and platelets, and a decrease in neutrophils were observed in the vehicle group. Furthermore, the expression of iNOS, E-selectin and the total level of NO in hepatic tissue, and soluble E-selectin in the plasma were significantly elevated in the vehicle group. Rosiglitazone pre-treatment prevented the increases in ALT (and AST), soluble E-selectin concentration, red blood cells and platelet counts. Moreover, rosiglitazone reduced over-expression of iNOS and the NO level, prevented the fall in neutrophil count and promoted the phosphorylation of iNOS in the liver. CONCLUSIONS: Pre-treatment with rosiglitazone ameliorated liver injury from severe DCS. This preventive effect may be partly mediated by stimulating endothelial NO production, improving endothelial function and limiting inflammatory processes.

Effects of high potassium chloride supplementation on water intake and bodyweight gains in pregnant and lactating mice.

Thirty-one ICR pregnant mice were assigned to a control or a potassium chloride (KCl) diet group to clarify the effects of KCl supplementation on water intake, bodyweight gains and serum components in pregnant and lactating mice, and 5% KCl was supplemented in KCl diets from 6.5 days post coitus to 1 or 14 days after parturition. Feed intake was not affected by treatment, but supplemental KCl decreased bodyweight gains of lactating mice and their neonatal mice. Water intake and urine volume of KCl supplemented mice were significantly higher than those of control mice during pregnancy and supplemental KCl decreased serum urea N in pregnant mice. Supplemental KCl increased water intake drastically in lactating mice immediately after parturition and increased serum K at 14 days after parturition. Histological alteration using hematoxylin-eosin was not found in the kidney of each mouse at 1 or 14 days after parturition. These results indicate that high KCl supplementation accelerates water intake in lactating mice and prevents bodyweight gains of maternal and neonatal mice during lactation.

Baseline and stress-induced plasma corticosterone concentrations of mice selectively bred for high voluntary wheel running.

The hypothalamic-pituitary-adrenal (HPA) axis is important in regulating energy metabolism and in mediating responses to stressors, including increasing energy availability during physical exercise. In addition, glucocorticoids act directly on the central nervous system and influence behavior, including locomotor activity. To explore potential changes in the HPA axis as animals evolve higher voluntary activity levels, we characterized plasma corticosterone (CORT) concentrations and adrenal mass in four replicate lines of house mice that had been selectively bred for high voluntary wheel running (HR lines) for 34 generations and in four nonselected control (C) lines. We determined CORT concentrations under baseline conditions and immediately after exposure to a novel stressor (40 min of physical restraint) in mice that were housed without access to wheels. Resting daytime CORT concentrations were approximately twice as high in HR as in C mice for both sexes. Physical restraint increased CORT to similar concentrations in HR and C mice; consequently, the proportional response to restraint was smaller in HR than in C animals. Adrenal mass did not significantly differ between HR and C mice. Females had significantly higher baseline and postrestraint CORT concentrations and significantly larger adrenal glands than males in both HR and C lines. Replicate lines showed significant variation in body mass, length, baseline CORT concentrations, and postrestraint CORT concentrations in one or both sexes. Among lines, both body mass and length were significantly negatively correlated with baseline CORT concentrations, suggesting that CORT suppresses growth. Our results suggest that selection for increased locomotor activity has caused correlated changes in the HPA axis, resulting in higher baseline CORT concentrations and, possibly, reduced stress responsiveness and a lower growth rate.

Use of the i-STAT portable clinical analyzer in mice.

The use of portable chemistry analyzers is an attractive option for obtaining clinical pathology panels in mice, because these analyzers require only small volumes of whole blood. However, in studies with other animals, portable analyzers do not always agree with results obtained using standard laboratory equipment. The authors evaluated the use of the i-STAT handheld portable clinical analyzer compared to the use of standard nonportable laboratory instruments in mice. As shown with other species, the i-STAT results did not always agree with standard laboratory instruments; however, the i-STAT does show reliability for certain chemistry assays.

Mixed disulphide formation in myoglobin of mouse (Mus musculus).

The myoglobin, isolated from murine skeletal muscles by chromatofocusing, showed the three components, one major and two minor, with different electrophoretic mobilities. The major component with the isoelectric point (pI) of 7.55 had one reactive SH/mole, while the others with pI of 7.32 and 7.16 showed none, which could be rendered fully reactive by treating the proteins with beta-mercaptoethanol. The three components were the same in their molecular weight (18 kDa), amino-acid composition with one Cys residue and oxygenation properties. By a sensitive high-performance liquid chromatography method, the occurrence of cysteine or glutathione mixed disulphide was verified in the two minor components. We conclude from these results and incubation experiments with low-molecular-weight thiols that the two minors were derived from the major by a mixed disulphide formation with either cysteine or glutathione of the cysteinyl SH at the 66th sequence.

Comparison of plasma endotoxin levels in germ-free, SPF and conventional laboratory animals (mice and rats).

Plasma endotoxin levels were examined in laboratory mice and rats sustained under germ-free (GF), SPF and conventional (CV) conditions. The values were 1.72 (GF mouse), 2.67 (SPF mouse), 2.44 (CV mouse), 2.05 (GF rat), 2.56 (SPF rat), and 3.13 pg/ml (CV rat). The GF animals showed the lowest levels, followed by SPF and CV animals, in that order. When SPF animals were transferred into the conventional condition (conventionalization), the plasma endotoxin levels changed slightly, but not significantly. The present study demonstrates that the levels of plasma endotoxin in healthy laboratory animals are relatively stable and are not affected by microbiological conditions.

Cyclosporin A is a hormonal immunomodulator. II. Mouse study.

The present study investigated the effects of hydrocortisone (HCA) and cyclosporin A (CS) on the wet weights of various target tissues and on the plasma levels of 6 steroids and cholesterol (CH) in Swiss mice of both sexes. The effects of CS on the weights of the spleen and forestomach, as viewed from their steroid dependencies in weight change, were different for each tissue and for each sex: CS effect on the male spleen was characterized as a mixture of a major androgenic element and a minor corticosteroid-like element, whereas that on the female spleen was scored as purely androgenic. Similarly, CS effects on the male and female forestomachs were interpreted respectively as estrogenic and androgenic in nature. Both the sole use of HCA (CS-free treatment) and the combined use of HCA and CS (CS-aided treatment) increased plasma testosterone (T) and plasma CH at the expense of other plasma steroids, though minor differences were detectable between the two treatments as regards the deviation profiles of 6 steroids and cholesterol with mice of both sexes. Plasma hydrocortisone (F) in males and plasma estradiol (E2) in females were consistently resistant to the depressing effects of the 2 immunosuppressants. In conclusion, the effect of CS on the mouse immune system, as judged from the response of the spleen, was to create a state of hyperandrogenism in favor of the production of immune unresponsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Optimized recirculation survival of mouse carrier erythrocytes.

Carrier mouse erythrocytes prepared by a hypotonic dialysis technique and reinjected into mice have a 24 hour survival of approximately 50%. Twenty-four hour survival can be improved substantially to 74% by removing the more fragile erythrocytes by a hypotonic wash treatment. The mean cell volume of the carriers prepared by this modification is significantly (p less than 0.01) different from cells prepared by the standard method with a isotonic wash treatment. Carriers prepared by the hypotonic treatment wash modification exhibit a different 50% hemolytic value (15% difference) from isotonically prepared carriers, and normal erythrocytes. Carrier-erythrocytes removed from mice 24 hour post-injection exhibit an osmotic profile that is independent of the treatment. Carriers were also prepared by another modification of the encapsulation procedure and held in a permeable state overnight before resealing and annealing. Carriers prepared in this manner showed a much lower 24 hour survival (13%).

Repetitive blood sampling in unrestrained and unstressed mice using a chronic indwelling right atrial catheterization apparatus.

A re-usable mobile catheterization apparatus was developed that permits multiple blood samples to be obtained from nonrestrained and unanesthetized mice. The collection end of the catheter is located outside the cage allowing the mouse to remain completely undisturbed prior to and during blood collection. The apparatus was used in adult mice surgically fitted under pentobarbital anesthesia with right atrial silastic catheters. Sample volume and collection frequency are easily controlled without subjecting the animal to repetitive trauma. Low plasma corticosterone concentrations confirmed the nonstressful quality of the technique. Full catheter patency in mice averaged 21.5 days. The tethering apparatus design was easily upscaled to accommodate use in adult rats.

Sex differences in the serum concentrations of testosterone in mice and hamsters during their critical periods of neural sexual differentiation.

Male and female mice and hamsters were decapitated 1-5 days after birth and serum concentrations of testosterone determined by radioimmunoassay. In the two species studied, serum levels of testosterone in male pups were significantly (P less than 0.05) higher than those obtained in female neonates. This lends support to the hypothesis that circulating levels of testosterone play an important role in the process of neural sexual differentiation in rodents. Moreover, the sex differences in serum concentrations of testosterone in neonatal rodents together with the detectable levels of testosterone in female neonates may suggest that androgenization is a dose-dependent phenomenon. Alternatively, they may indicate that a minimum concentration of the steroid must be present for androgenization to occur during the critical period of neural sexual differentiation and that this 'threshold' is exceeded in male but not in female rodents.