Reaction Kinetics Modeling of eHsp70 Induced by Norepinephrine in Response to Exercise Stress.

Exercise elicits a systemic adaptation reaction, involving both neuroendocrine and cellular/paracrine stress responses, exemplified by the sympathoadrenergic activity and the release of cellular Hsp70 into the circulation. Regular sports training is known to result in increased fitness. In this study, we characterized the plasma norepinephrine and Hsp70 levels and modeled their relationship in response to exercise stress by bicycle ergometer in 12 trained judoka athletes and in 10 healthy controls. Resting norepinephrine was similar in both groups, whereas Hsp70 was significantly higher in controls compared to athletes. Intense exercise load induced both norepinephrine and Hsp70 elevation. However, both norepinephrine and Hsp70 were significantly lower in athletes compared to the control group. A reaction kinetic model was developed that provided a quantitative description of norepinephrine-facilitated extracellular Hsp70 release, congruent with the experimental data. Our study indicates that exercise-induced norepinephrine and extracellular Hsp70 may be coordinated responses to physiological stress, which are robustly affected by regular sports activity.

A cellular defense memory imprinted by early life toxic stress.

Stress exposure early in life is implicated in various behavioural and somatic diseases. Experiences during the critical perinatal period form permanent, imprinted memories promoting adult survival. Although imprinting is widely recognized to dictate behaviour, whether it actuates specific transcriptional responses at the cellular level is unknown. Here we report that in response to early life stresses, Caenorhabditis elegans nematodes form an imprinted cellular defense memory. We show that exposing newly-born worms to toxic antimycin A and paraquat, respectively, stimulates the expression of toxin-specific cytoprotective reporters. Toxin exposure also induces avoidance of the toxin-containing bacterial lawn. In contrast, adult worms do not exhibit aversive behaviour towards stress-associated bacterial sensory cues. However, the mere re-encounter with the same cues reactivates the previously induced cytoprotective reporters. Learned adult defenses require memory formation during the L1 larval stage and do not appear to confer increased protection against the toxin. Thus, exposure of C. elegans to toxic stresses in the critical period elicits adaptive behavioural and cytoprotective responses, which do not form imprinted aversive behaviour, but imprint a cytoprotective memory. Our findings identify a novel form of imprinting and suggest that imprinted molecular defenses might underlie various pathophysiological alterations related to early life stress.

One-Day Use of Preoperative Topical Nonsteroidal Anti-Inflammatory Drug Prevents Intraoperative Prostaglandin Level Elevation During Femtosecond Laser-Assisted Cataract Surgery.

PURPOSE: To determine if pretreatment with topical nonsteroidal anti-inflammatory drug (NSAID) prior to femtosecond laser-assisted cataract surgery (FLACS) prevents intraoperative prostaglandin level elevation as a potential risk factor of postoperative complications. PATIENTS AND METHODS: Thirty-six patients with clinically significant cataract and without any concomitant general or ophthalmic disease were enrolled into the three age-matched groups of the study. The mean age of the patients was 62.3 ± 13.1 years. The first group of patients underwent traditional phacoemulsification (Control group), on the second group of patients FLACS was performed, and the third group of patients received topical 0.1% nepafenac pretreatment for 1one day prior to FLACS. Before the phacoemulsification part of the cataract surgery, approximately 110 µL of aqueous humor was collected in all groups. Total prostaglandin concentrations of the collected aqueous humor samples were evaluated by enzyme immunoassay (EIA). RESULTS: The mean of the total prostaglandin concentrations of the aqueous humor samples was 208.8 ± 140.5 pg/mL in patients in the control group, 1449.1 ± 1019.7 pg/mL in the FLACS group (p > 0.001), and 92.2 ± 51.7 pg/mL in the group pretreated with topical NSAID before the FLACS (p > 0.001 compared to FLACS; p > 0.01 compared to control), respectively. CONCLUSIONS: FLACS surgery increases intracameral prostaglandin concentration. However, using preoperative 1-day-long nonsteroid anti-inflammatory drops prior to FLACS, this intraoperative increase diminishes. Our study raises the possibility that NSAID pretreatment may be routinely administered before FLACS cataract surgeries to achieve a further decrease in the potential complications of increased total prostaglandin concentration during FLACS surgeries.