Review of the evidence of radioprotective potential of creatine and arginine as dietary supplements.

PURPOSE: Creatine (Cr) and l-arginine are naturally occurring guanidino compounds, commonly used as ergogenic dietary supplements. Creatine and l-arginine exhibit also a number of non-energy-related features, such as antioxidant, anti-apoptotic, and anti-inflammatory properties, which contribute to their protective action against oxidative stress (OS). In this regard, there are a number of studies emphasizing the protective effect of Cr against OS, which develops in the process of aging, increased physical loads as part of athletes' workouts, as well as a number of neurological diseases and toxic effects associated with xenobiotics and UV irradiation. Against this backdrop, and since ionizing radiation causes OS in cells, leading to radiotoxicity, there is an increasing interest to understand whether Cr has the full potential to serve as an effective radioprotective agent. The extensive literature search did not provide any data on this issue. In this narrative review, we have summarized some of our own experimental data published over the last years addressing the respective radioprotective effects of Cr. Next, we have additionally reviewed the existing data on the radiomodifying effects of l-arginine presented earlier by other research groups. CONCLUSIONS: Creatine possesses significant radioprotective potential including: (1) radioprotective effect on the survival rate of rats subjected to acute whole-body X-ray irradiation in a LD70/30 dose of 6.5 Gy, (2) radioprotective effect on the population composition of peripheral blood cells, (3) radioprotective effect on the DNA damage of peripheral blood mononuclear cells, (4) radioprotective effect on the hepatocyte nucleus-nucleolar apparatus, and (5) radioprotective effect on the brain and liver Cr-Cr kinase systems of the respective animals. Taking into account these cytoprotective, gene-protective, hepatoprotective and energy-stimulating features of Cr, as well as its significant radioprotective effect on the survival rate of rats, it can be considered as a potentially promising radioprotector for further preclinical and clinical studies. The review of the currently available data on radiomodifying effects of l-arginine has indicated its significant potential as a radioprotector, radiomitigator, and radiosensitizer. However, to prove the effectiveness of arginine (Arg) as a radioprotective agent, it appears necessary to expand and deepen the relevant preclinical studies, and, most importantly, increase the number of proof-of-concept clinical trials, which are evidently lacking as of now.

Ovarian cancer cells regulate their mitochondrial content and high mitochondrial content is associated with a poor prognosis.

Most cancer patients ultimately die from the consequences of distant metastases. As metastasis formation consumes energy mitochondria play an important role during this process as they are the most important cellular organelle to synthesise the energy rich substrate ATP, which provides the necessary energy to enable distant metastasis formation. However, mitochondria are also important for the execution of apoptosis, a process which limits metastasis formation. We therefore wanted to investigate the mitochondrial content in ovarian cancer cells and link its presence to the patient's prognosis in order to analyse which of the two opposing functions of mitochondria dominates during the malignant progression of ovarian cancer. Monoclonal antibodies directed against different mitochondrial specific proteins, namely heat shock proteins 60 (HSP60), fumarase and succinic dehydrogenase, were used in immunohistochemistry in preliminary experiments to identify the antibody most suited to detect mitochondria in ovarian cancer cells in clinical tissue samples. The clearest staining pattern, which even delineated individual mitochondria, was seen with the anti-HSP60 antibody, which was used for the subsequent clinical study staining primary ovarian cancers (n = 155), borderline tumours (n = 24) and recurrent ovarian cancers (n = 26). The staining results were semi-quantitatively scored into three groups according to their mitochondrial content: low (n = 26), intermediate (n = 50) and high (n = 84). Survival analysis showed that high mitochondrial content correlated with a statistically significant overall reduced survival rate In addition to the clinical tissue samples, mitochondrial content was analysed in ovarian cancer cells grown in vitro (cell lines: OVCAR8, SKOV3, OVCAR3 and COV644) and in vivo in severe combined immunodeficiency (SCID) mice.In in vivo grown SKOV3 and OVCAR8 cells, the number of mitochondria positive cells was markedly down-regulated compared to the in vitro grown cells indicating that mitochondrial number is subject to regulatory processes. As high mitochondrial content is associated with a poor prognosis, the provision of high energy substrates by the mitochondria seems to be more important for metastasis formation than the inhibition of apoptotic cell death, which is also mediated by mitochondria. In vivo and in vitro grown human ovarian cancer cells showed that the mitochondrial content is highly adaptable to the growth condition of the cancer cells.

The role of women scientists in the development of ultrashort pulsed laser technology-based biomedical research in Armenia.

PURPOSE: To describe the contribution of women scientists in the development of biomedical studies conducted on research facilities based on the ultrashort pulsed laser technologies in Armenia. CONCLUSION: Given the opportunities provided by the ultrashort pulsed laser driven two-photon microscopy and electron beam linac facilities at CANDLE Synchrotron Research Institute, the Armenian women scientists initiated and conducted interdisciplinary research to understand of the biomedical effects of ultrashort pulsed electron beam irradiation, as well as to experience and apply the advantages of the two-photon microscopy in their fields of research. Women scientists had a crucial role and unique impact in the development of ultrashort pulsed laser technology-based biomedical studies in Armenia.

In memory of Margarita Malakyan, a bright person and inquisitive scientist.

PURPOSE: To describe the contribution of Margarita Malakyan to the development of radiation biology in Armenia and how her multidisciplinary collaboration with chemists, physicists and biologists around the world led to the development of radioprotectors and radiosensitizers of different origins. CONCLUSION: Margarita Malakyan was a very active and initiative woman, a radiobiologist, whose hard work and enthusiasm led to the establishment of a very constructive scientific network and to the development of newly synthesized metal compounds. During her short but very productive life, the synthesis, characterization, as well as toxicity and radioprotective studies of different compounds led to the suggestion of a number of metal complexes of Schiff bases as effective radioprotective agents and radiosensitizers.

Positive Affect Moderates the Relationship Between Salivary Testosterone and a Health Behavior Composite in University Females.

BACKGROUND: Testosterone is released in both men and women and plays an important role in social functioning and motivation. Greater testosterone in women has been associated with negative physical health outcomes, while lower testosterone has been associated with psychological disorders. The following cross-sectional study examined the contribution of salivary testosterone, positive and negative affect, and demographic variables in predicting a composite health behavior score (cigarette use, hours of sleep, fruit/vegetable intake, following an exercise routine). METHOD: The sample (mean age 21.17, SD = 6.13) consisted of 87 female university students asked to complete a demographic and lifestyle behavior questionnaire, the Positive and Negative Affect Schedule, and provide a saliva sample. Participants self-identified as Latina (37.9%), European American (32.2%), Asian American (5.7%), African American (4.6%), or Mixed/other (19.5%). Hierarchical regression analyses were used to examine whether positive and negative affect served as a moderator between salivary testosterone and a health behavior composite. RESULTS: Results indicated that positive affect moderated the relationship between salivary testosterone and the composite health behavior score (t = - 2.42, p = .018, Adj. R2 = .21, F (5, 81) = 5.07, p < .001) such that the healthiest behaviors were observed in participants with high positive affect and low salivary testosterone. Findings remained after adjusting for oral contraceptive use, income level, relationship status, and ethnicity. CONCLUSIONS: These results provide a preliminary foundation for future research examining the interplay of neuroendocrine function, psychological factors (i.e., positive affect), and behavior. Further empirical studies can focus on expanding this research in larger, representative samples.