Purpose To evaluate ongoing metabolic changes during a 48-h competitive run and a 48-h recovery period, with focus on potential health risks exemplified by heart and skeletal muscle damage biomarkers and oxidative stress-related indices. Methods Blood samples were taken before the race, after 12, 24, and 48 h of running, and after 24 and 48 h of recovery from male amateur runners (N = 7, age 35–59 years, VO_2max mean ± SD 57.0 ± 4.0 ml kg⁻¹ min⁻¹, total distance covered 183–320 km). The samples were analyzed for morphology, acid–base and electrolyte balance, iron status, lipid profile, interleukin-6, high-sensitivity C-reactive protein, N-terminal pro-brain-type natriuretic peptide, high-sensitivity cardiac troponin T, non-enzymatic antioxidants, activities of selected enzymes including antioxidant enzymes, and total antioxidant status. Results The sustained ultra-endurance run caused hypocapnic alkalosis with slight hyperkalemia and hypocalcemia, but no hyponatremia. Blood biochemistry showed severe muscle but not liver damage, and an acute inflammatory response. These effects were evidenced by leukocytosis, several fold rises in interleukin-6 and high sensitivity C-reactive protein, extreme elevations in serum levels of muscle enzymes, and marked increases in cardiac biomarker levels. Most of the changes dissolved during the 48 h post-race recovery. Neither the iron pool, nor erythropoiesis, nor pro-oxidant/antioxidant balance were substantially affected. Conclusions The changes consequent on the ultra-endurance run do not pose a serious health risk in men who begin their endeavor with ultra-endurance running in mid-life. There is some circumstantial evidence that hyperventilatory hypocapnia may modulate inflammatory response by stimulating the release of interleukin-6 from working skeletal muscles.

Rationale Propensity for drug dependence shows great diversity that is related to intrinsic neurobiological factors. This diversity is important both for the understanding of these traits and for the development of therapies. Objectives The goals of the study were (1) to define, using ultrasonic vocalization characteristics, inter-individual differences in rats’ propensity for sensitization to amphetamine, (2) to test whether possible resistance to this effect could be overcome with repetitive treatment, and (3) to seek useful predictors of the propensity. Methods Rats were subject to tests meant to characterize their anxiety, pain sensitivity, and responses to novelty and natural rewards. Then they were subject to the so-called two-injection protocol of sensitization (using amphetamine) followed by 2 weeks of daily amphetamine treatment, 2-week withdrawal, and final amphetamine challenge. The development and outcome of sensitization were monitored by measuring 50-kHz vocalization. Results The two-injection protocol yielded three patterns of changes in the frequency-modulated 50-kHz vocalization response to amphetamine. These patterns persisted after completion of the extended drug treatment. Rats with lower sensitivity to pain or with longer latency of their vocalization response to the first drug exposure showed an increased propensity for ultrasonic vocalization sensitization. Conclusion Vulnerability to sensitization of frequency-modulated 50-kHz vocalization response of Sprague–Dawley rats to amphetamine, which supposedly reflects rats’ propensity for amphetamine dependence, shows large inter-individual diversity. Resistance to this effect, which is evident in a majority of the rats, cannot be overcome even with prolonged intermittent drug treatment under the conditions (novelty) that promote sensitization.