Introduction: The met-enkephalin (1-5 Adrenorphin) and tridecactide (alpha-corticotropin 1-13) combination is used in the multiple sclerosis (MS) immuno-modulatory treatment. A testing of cytogenetic effects of met-enkephalin resulted in reductions of lymphocytic aberrations in the in the lymphocytes of the peripheral blood (PBL) of patients with immune-mediated diseases. The aim of this research is to evaluate the in vitro effects of the combination of the met-enkephalin and tridecactide on the number and the type of chromosome aberrations in PBL of the MS patients. Methods: We used blood samples from seven female patients with the diagnosis multiple sclerosis based on a McDonald Diagnostic Criteria. The tested combination, met-enkephalin and alpha-ACTH 1-13 was added at three different concentrations and constant volume. Results: Results showed that the combination of tested substances did not reduce the number of structural aberrations, although the treatment did not result in severe aberrations such as ring, fragmented, and dicentric chromosomes. Furthermore, it elicited an increase in the number of numerical aberrations and aneuploidy after the treatment with the test combo. Conclusion: As the changes in ploidy significantly change the DNA as well as the biochemical cell phenotype, we concluded that more research in this field should be conducted, including both toxicological as well as the pharmacodynamic considerations.

Pulmonary inflammation can contribute to the development of lung cancer in humans. We investigated whether pulmonary inflammation alters the genotoxicity of polycyclic aromatic hydrocarbons (PAHs) in the lungs of mice and what mechanisms are involved. To model nonallergic acute inflammation, mice were exposed intranasally to lipopolysaccharide (LPS; 20 µg/mouse) and then instilled intratracheally with benzo[a]pyrene (BaP; 0.5 mg/mouse). BaP-DNA adduct levels, measured by 32P-postlabeling analysis, were approximately 3-fold higher in the lungs of LPS/BaP-treated mice than in mice treated with BaP alone. Pulmonary Cyp1a1 enzyme activity was decreased in LPS/BaP-treated mice relative to BaP-treated mice suggesting that pulmonary inflammation impacted on BaP-induced Cyp1a1 activity in the lung. Our results showed that Cyp1a1 appears to be important for BaP detoxification in vivo and that the decrease of pulmonary Cyp1a1 activity in LPS/BaP-treated mice results in a decrease of pulmonary BaP detoxification, thereby enhancing BaP genotoxicity (ie, DNA adduct formation) in the lung. Because less BaP was detoxified by Cyp1a1 in the lungs of LPS/BaP-treated mice, more BaP circulated via the blood to extrapulmonary tissues relative to mice treated with BaP only. Indeed, we observed higher BaP-DNA adduct levels in livers of LPS/BaP-treated mice compared with BaP-treated mice. Our results indicate that pulmonary inflammation could be a critical determinant in the induction of genotoxicity in the lung by PAHs like BaP. Cyp1a1 appears to be involved in both BaP bioactivation and detoxification although the contribution of other enzymes to BaP-DNA adduct formation in lung and liver under inflammatory conditions remains to be explored.

Objective To test whether more physiologically assessed hot flashes were associated with greater connectivity in the default mode network (DMN), the network of brain regions active during rest. We particularly focus on DMN networks supporting the hippocampus as this region is rich in estrogen receptors and has previously been linked to hot flashes. Design Women underwent 24 hours of physiologic and diary hot flash monitoring, functional magnetic resonance imaging, 72 hours of sleep actigraphy monitoring, a blood draw, questionnaires, and physical measures. Setting Community Participants Twenty midlife women ages 40–60 with their uterus and both ovaries and not taking hormone therapy Interventions None Main outcome measures DMN functional connectivity Results Controlling for age, race, education, a greater number of physiologically-monitored hot flashes were associated with greater DMN connectivity [beta, B (standard error, SE)=.004 (.002), p<.05], particularly hippocampal DMN connectivity [B(SE)=.005 (.002), p<.05]. Findings were most pronounced for sleep physiologic hot flashes [with hippocampal DMN, B(SE)= .02 (.007), p<0.01]. Associations persisted additionally controlling for sleep, depressive symptoms, and serum estradiol concentrations. Conclusions More physiologically-monitored hot flashes were associated with greater DMN connectivity, particularly networks supporting the hippocampus. Findings were most pronounced for sleep hot flashes. Findings underscore the importance of continued investigation of the central nervous system in efforts to understand this classic menopausal phenomenon.