The American journal of physiology
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This study attempted to ascertain whether the ischemic damage to neurons and monoamine overload in brain that occur during rat heatstroke can be attenuated by heat shock protein (HSP) 72 induction. Effects of heatstroke on mean arterial pressure (MAP), cerebral blood flow (CBF), brain dopamine (DA) and serotonin (5-HT) release, and neural damage score were assayed in rats 0, 16, or 48 h after heat shock (42 degrees C for 15 min) or chemical stress (5 mg/kg sodium arsenite ip). Brain HSP 72 in rats after heat shock or chemical stress was detected by Western blot, and brain monoamine was determined by a microdialysis probe combined with high-performance liquid chromatography. ⋯ Prior heat shock or chemical stress conferred significant protection against heatstroke-induced hyperthermia, arterial hypotension, cerebral ischemia, cerebral DA and 5-HT overload, and neural damage and correlated with expression of HSP 72 in brain at 16 h. However, at 48 h, when HSP 72 expression returned to basal values, the above responses that occurred during the onset of heatstroke were indistinguishable between the two groups (0 h vs. 48 h). These results lead to the hypothesis that the brain can be preconditioned by thermal or chemical injury, that this preconditioning will induce HSP 72, and that HSP 72 induction will correlate quite well with anatomic, histochemical, and hemodynamic protection in rat heatstroke.
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We have measured plasma volume expansion (Evans blue and hematocrit changes) and hemodynamic responses in conscious hemorrhaged and normovolemic splenectomized sheep after a 30-min infusion of either 20 ml/kg of diaspirin cross-linked hemoglobin (DCLHb), 20 ml/kg of human albumin (Alb), or 60 ml/kg of a solution of Ringer lactate (RL). All regimens expanded blood volume and increased blood pressure and cardiac output after hemorrhage. However, only 15 +/- 3% of the infused volume of RL was evident as intravascular expansion 10-min postinfusion, compared with 67 +/- 16% and 139 +/- 139% for Alb and DCLHb, respectively. ⋯ The better volume expansion with DCLHb may be due to greater mobilization of endogenous interstitial protein or reduced transcapillary loss as total intravascular endogenous plasma protein increased after infusion of DCLHb, whereas there was an apparent loss of endogenous intravascular protein after infusions of Alb and RL. Vasoconstriction by DCLHb is one mechanism that could lower blood-to-tissue transport of fluid and protein. In addition to its oxygen-carrying capacity and vasoactivity, DCLHb is associated with volume expansion properties out of proportion to its colloid osmotic pressure.
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Fever is a phylogenetically ancient response that is associated with improved survival in acute infections. In endothermic animals, fever is induced by a set of pyrogenic cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, and IL-6] that are also essential for survival in acute infections. ⋯ TNF-alpha levels were increased predominantly in liver, IL-1beta levels were higher in lung, and IL-6 levels were widely increased in multiple organs in the warmer mice. This demonstrates that the thermal component of fever may directly contribute to shaping the host response by regulating the timing, magnitude, and tissue distribution of cytokine generation during the acute-phase response.
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Using the conditionally immortalized human cell line tsFHI, we have investigated the role of cyclin-dependent kinase inhibitors (CKIs) in intestinal epithelial cell differentiation. Expression of cyclins, cyclin-dependent kinases (Cdk), and CKIs was examined under conditions promoting growth, growth arrest, or expression of differentiated traits. Formation of complexes among cell cycle regulatory proteins and their kinase activities were also investigated. ⋯ With differentiation, p21 and p27 were strongly induced, but with different kinetics: the p21 increase was rapid but transient and the p27 increase was delayed but sustained. Our results suggest that the function of p16 is primarily to inhibit cyclin D-associated kinases, making tsFHI cells dependent on cyclin E-Cdk2 for pRb phosphorylation and G1/S progression. Furthermore, they indicate that p21 is the main CKI involved in irreversible growth arrest during the early stages of cell differentiation in association with D-type cyclins, cyclin E, and Cdk2, whereas p27 may induce or stabilize expression of differentiated traits acting independently of cyclin-Cdk function.
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Brain swelling after acute hyponatremia in prepubescent rats, in contrast to adults, has recently been associated with an increase in brain sodium and a high mortality that could be prevented by preadministration of testosterone. To reexamine the effect of acute hyponatremia in young brain, we measured brain water and solute content in prepubescent rats after induction of hyponatremia over 4 h with water and arginine vasopressin. An 18% decrease in plasma sodium was associated with a 13% increase in brain water and a decrease in brain sodium and glutamate contents. ⋯ Brain sodium and potassium contents were significantly reduced in comparison to normonatremia in testosterone-pretreated but not estrogen-pretreated animals. However, there was no difference between estrogen-pretreated and testosterone-pretreated groups in mortality or in brain contents of water, electrolytes, or major organic osmolytes. In conclusion, we found that brain adaptation to acute hyponatremia in prepubescent rats is similar to that observed in adults.