The Beneficial Effects of Pterostilbene on Post-Thawed Bovine Spermatozoa.

Reactive Oxygen Species (ROS), primarily produced by cellular metabolism, are highly reactive molecules that modify cellular compounds. During sperm preparation in Assisted Reproductive Techniques (ARTs), intrinsic and extrinsic sources of ROS can impact spermatozoa's oxidative status. The modification of the media with compounds that enhance sperm quality characteristics is of great significance. The current study investigated the effect of pterostilbene, a phenolic compound, on bovine sperm quality. Cryopreserved spermatozoa from six bulls were thawed, supplemented with pterostilbene (0, 10 µΜ, 25 µΜ) and incubated for 60 min and 240 min. Spermatozoa were analyzed in terms of motility, viability, acrosomal status and intracellular concentration of superoxide anion in each time point. The incubation of spermatozoa with 25 µΜ pterostilbene resulted in the preservation of quality parameters through superoxide anion mitigation, while its presence in capacitating conditions resulted in higher percentage of acrosome-reacted spermatozoa. The results of the present study indicate that the addition of pterostilbene prevents oxidative insult to spermatozoa and preserves the sperm quality parameters.

Vitamin D Status in Osteoporotic and Diabetic Patients and Athletic Healthy Individuals from Northern Greece.

Background: Vitamin D deficiency is recognised as a pandemic in the developed world. However, the importance of prudent sun exposure tends to be overlooked, which is responsible for this pandemic. Methods: We investigated the vitamin D status in 326 adults, 165 females and 161 males: 99 Osteoporosis patients, 53 Type 1 Diabetes patients, 51 Type 2 Diabetes patients, and 123 Athletic Healthy individuals, from Northern Greece, through the measurement of total calcidiol in winter and summer by immunoenzymatic assay. Results: In the Whole Sample 23.31% had severe deficiency, 13.50% mild deficiency, 17.48% insufficiency, and 45.71% adequacy at the end of winter. Mean concentrations differed significantly (p <0.001) between males and females. The prevalence of deficiency in the young was significantly lower than in the middle-aged (p = 0.004) and in the elderly (p <0.001), while it was significantly lower (p = 0.014) in the middle-aged than in the elderly. The best vitamin D status was found in the Athletic Healthy individuals, followed by the Type 1 and Type 2 Diabetic patients, while Osteoporotic patients had the poorest status. The difference in mean concentrations between winter and summer was significant (p <0.001). Conclusions: Vitamin D status deteriorated with increasing age and it was better in males than in females. Our findings suggest that outdoor physical activity in a Mediterranean country can cover the vitamin D needs of the young and the middle-aged, but not of the elderly, without the need for dietary supplements.

CYP17A1 and Androgen-Receptor Expression in Prostate Carcinoma Tissues and Cancer Cell Lines.

BACKGROUND: CYP17A1 is involved in the steroidogenesis of dehydroepiandrosterone and androstenedione. CYP17A is a target for the hormonal treatment of prostate cancer (PCa). OBJECTIVES: To investigate the role of CYP17A1 as a driver of PCa growth. MATERIALS AND METHODS: We examined the expression of CYP17A1 and of androgen receptors (AR) in PCa specimens and in PCa cell lines. RESULTS: CYP17A1 was strongly expressed in the cytoplasm of PCa cells (median 50% of cancer cells, range 0-100%). The nuclear AR expression in cancer cells was directly related with CYP17A1 (p < 0.0001, r = 0.51). The hormone dependent 22Rv1 cell line expressed the CYP17A1 and AR protein and mRNA, in contrast to the PC3 and DU145 cell lines (p < 0.0001). Testosterone and dexamethasone induced nuclear expression of AR and this effect was abolished by abiraterone. CYP17A1 levels were not affected by the incubation with testosterone, while abiraterone significantly reduced its expression. Abiraterone reduced the growth rate and migration of testosterone stimulated 22Rv1 cells. CONCLUSIONS: CYP17A1 is strongly expressed in half about of human prostate carcinomas, implying an intracellular androgen synthesis by cancer cells. Abiraterone effectively blocked nuclear accumulation of AR and suppressed CYP17A1 expression. CYP17A1 may function as a biomarker to select the best hormonal anticancer therapy.

Regional disparities in cancer mortality across the rural-urban axis: a case study from north-eastern Greece.

INTRODUCTION: The aim of this study was to identify differences in cancer mortality in north-eastern Greece, to describe potential drivers operating at the population level and to propose practical interventions and mitigation strategies. METHODS: Cancer mortality data were collected from local registries using the WHO 10th edition of International Classification of Disease (ICD-10). The direct standardization method was used to address demographic differences in the two regions, with the Standard European Population as reference. Rate ratios (RR) were employed for comparisons and 95% confidence intervals (95%CI) were calculated according to the Poisson approximation method. RESULTS: An increased risk of digestive system cancers (excluding liver neoplasms) was observed in rural versus urban areas (RR=1.25, 95%CI=1.02-1.54). Stomach cancer, in particular, was more prevalent in the older cohorts (>65 years), suggesting a historical epidemiological perspective. A more pronounced discrepancy was observed for prostate cancer mortality (RR=1.86, 95%CI=1.10-3.14), indicating a strong positive correlation with rurality. CONCLUSIONS: Cancer mortality disparities have been observed between rural and urban regions of north-eastern Greece. Health promotion and education, including improved access to medical facilities and early cancer screening, can help mitigate the burden and extend survival rates. Decreasing cancer staging at the time of diagnosis and reversing social and economic inequalities is key for combating these types of malignancy.

Survival Fraction at 2 Gy and γH2AX Expression Kinetics in Peripheral Blood Lymphocytes From Cancer Patients: Relationship With Acute Radiation-Induced Toxicities.

PURPOSE: Predictive assays for acute radiation toxicities would be clinically relevant in radiation oncology. We prospectively examined the predictive role of the survival fraction at 2 Gy (SF2) and of γH2AX (double-strand break [DSB] DNA marker) expression kinetics in peripheral blood mononuclear cells (PBMCs) from cancer patients before radiation therapy. METHODS AND MATERIALS: SF2 was measured with Trypan Blue assay in the PBMCs from 89 cancer patients undergoing radiation therapy at 4 hours (SF2[4h]) and 24 hours (SF2[24h]) after ex vivo irradiation. Using Western blot analysis and band densitometry, we further assessed the expression of γH2AX in PBMC DNA at 0 hours, 30 minutes, and 4 hours (33 patients) and 0 hour, 4 hours, and 24 hours (56 patients), following ex vivo irradiation with 2 Gy. Appropriate ratios were used to characterize each patient, and these were retrospectively correlated with early radiation therapy toxicity grade. RESULTS: The SF2(4h) was inversely correlated with the toxicity grade (P=.006). The γH2AX-ratio(30min) (band density of irradiated/non-irradiated cells at 30 minutes) revealed, similarly, a significant inverse association (P=.0001). The DSB DNA repair rate from 30 minutes to 4 hours, calculated as the relative RγH2AX-ratio (γH2AX-ratio(4h)/γH2AX-ratio(30min)) showed a significant direct association with high toxicity grade (P=.01). CONCLUSIONS: Our results suggest that SF2 is a significant radiation sensitivity index for patients undergoing radiation therapy. γH2AX Western blot densitometry analysis provided 2 important markers of normal tissue radiation sensitivity. Low γH2AX expression at 30 minutes was linked with high toxicity grade, suggesting that poor γH2AX repair activity within a time frame of 30 minutes after irradiation predicts for poor radiation tolerance. On the other hand, rapid γH2AX content restoration at 4 hours after irradiation, compatible with efficient DSB repair ability, predicts for increased radiation tolerance.

Antitumour and cytogenetic effects of modified steroidal derivatives of propenoic acid: in vivo/in vitro studies.

BACKGROUND: Modified steroidal derivatives (PK11-PK14) of p-bis(2-chloroethyl)aminophenyl propenate (PK15) were used to study their antitumour activity on Lewis lung carcinoma (LLC) and their effect on sister chromatid exchanges (SCEs) and human lymphocyte proliferation kinetics. MATERIALS AND METHODS: LLC was tested in this study. C57BL mice were used for in vivo chemotherapy evaluation and the antitumour activity was assessed. Lymphocyte cultures were used to study the genotoxic effect in vitro. RESULTS: PK15 and PK11 were the most effective against LLC, causing significant inhibition of tumour growth. PK11 and PK15 induced significant increase in SCE rates. A correlation was observed between the cytogenetic effect and the antitumour effectiveness. CONCLUSION: The order of the antitumour effectiveness of PK11-PK15 resembled the order of the cytogenetic damage induced by the same compounds in vitro.

Socio-demographic risks of child injury in a Greek region.

UNLABELLED: Child injuries are a growing global public health problem and the aim of this research was to study child accidents, their causes and risk factors in a northern part of Greece, Thrace. METHODS: 1,516 high school children completed an anonymous questionnaire regarding the cause, type, activity before the accident, and result of their accident. RESULTS: The Chi square method showed a high correlation between accidents and variables such as gender (OR .55, 95% CI: .437-.687, P < .001), grade (P < .05), maternal education level (P < .001), paternal education level (P < .001), and social group each child belongs to (P < .001). The odds ratio was 3.3 (95% CI: 1.760-6.296) for Non-natives compared with Native Christians and Native Muslims. The latter had half odds in comparison with Native Christians (OR .4, 95% CI: .328-.545). CONCLUSIONS: Young boys (7th grade), non-natives, and children whose parents received higher education were at greater risk of being injured.

Frequency of genetic diseases and health coverage of children requiring admission in a general pediatric clinic of northern Greece.

BACKGROUND: In order to estimate the causes of pediatric morbidity in our area, with particular emphasis on diseases with a genetic background, we retrospectively categorized the admissions of all children hospitalized in the Department of Pediatrics of the University General Hospital of Alexandroupolis, in the area of Evros, Thrace, Greece over the three year period 2005-2007. Finally, in order to guide health care administrators to improve the delivery of pediatric health care services, we estimated the percentage of hospitalized children who were uninsured and the type of health insurance of those who had medical coverage. PATIENTS AND METHODS: The causes of admission, as recorded in the medical records were categorized in terms of the major organ and/or system involved and/or the underlying pathology, with emphasis on diseases with a genetic background. Duplicate admissions, i.e., admissions of the same child for the same underlying disease were excluded. Additional information recorded was age, sex, and type of health insurance of all admitted children. Distribution of the causes of admission by study year was compared by chi-square. A p value < 0.05 was considered significant. RESULTS: Over the study period, there were 4,947 admissions in 2,818 boys and 2,129 girls. Respiratory diseases were the most common accounting for 30%, while infectious diseases followed with 26.4%. The frequency of chromosomal abnormalities among the hospitalized children was only 0.06%. However, if we consider diseases with an underlying genetic background, this percentage rises to 5%. Approximately 10.3% of the admitted children had no health insurance. CONCLUSIONS: The percentage of children hospitalized in our area due to a disease with an underlying genetic background was 5%. This percentage pertains to a Department of Pediatrics that has no inpatient subspecialty units and which is located within a General hospital, because hospitalizations for genetic diseases are more frequent in specialized pediatric hospitals, with competence in clinical genetics. The double figure of uninsured children is worrisome and dictates the need for governmental efforts for universal pediatric health coverage in our country.

Chromosome instability in patients with chronic renal failure.

OBJECTIVE: The aim of this study was to investigate the frequency of sister chromatid exchanges (SCEs), the presence of cytostaticity, cytotoxicity, and therefore, the possible genetic instability in patients with chronic renal failure (CRF) in human cultured peripheral blood lymphocytes. METHODS: Peripheral blood lymphocytes were cultured from 32 patients with CRF (average 55.2 years) and 18 healthy blood donors (average 44.6 years), and the SCE method was applied afterward. The increase in SCE frequency was evaluated as an immediate DNA damage index, while the reduction in the values of the proliferating rate indices was evaluated as a cytostatic index and the mitotic indices as a cytotoxic index was also measured. RESULTS: A significant increase in the SCE frequencies along with a significant reduction in mitotic indices was observed in patients with CRF compared with the controls. It is notable that there was no significant difference in SCE levels among patients with CRF and cancer, and patients with CRF alone. CONCLUSIONS: This study illustrates increased genetic instability in patients with CRF. These results could also be of a great importance in early diagnosis to prognosticate a possible generation of neoplasm in the future.

Is psychopathology related to children's unintentional injury?

This research aimed to study children's psychopathology and unintentional accidents in Thrace, northern Greece. We examined whether there was a correlation between each risk factor of the research and the dependent variables: 1) minor accidents, 2) serious accidents that required Emergency Room attendance (ER accidents), 3) serious accidents that led to hospital admission (admission accidents). High school children (n = 1,516) completed an anonymous questionnaire regarding the cause of their accident, as well as the "Strengths and difficulties questionnaire" (SDQ) by Goodman. The results indicate that sex, conduct disorders, hyperactivity, and abnormal score in SDQ were important risk factors for minor injuries and continued to be important risk factors for ER accidents. Sex, conduct disorders, hyperactivity, peer-problems, and abnormal score in SDQ were important risk factors for the most serious accidents (admission accidents). Because major accidents can result in serious health problems or disability, attention should be paid to the risk factors found.

Cytogenetic and antineoplastic effects of modified steroidal alkylators.

INTRODUCTION: The aim of this study was to design new potentially antineoplastic agents by combining nitrogen mustard with steroidal skeleton, in an effort to improve specificity and simultaneously to reduce systemic toxicity. The steroidal part is aimed to act as a biological platform enabling the alkylating moiety to approach its site of action by altering its physicochemical properties. MATERIALS AND METHODS: The compounds tested have, as alkylating agents, either p-N,N-bis(2-chloroethyl)aminophenyl-butyrate or p-N,N-bis(2-chloroethyl)aminophenyl-acetate esterified with a modified steroidal nucleus. The four newly synthesized compounds were compared on a molar basis, regarding their ability to induce sister chromatid exchanges and modify proliferation rate indices in cultured human lymphocytes. Life span of BDF1 mice inoculated with L1210 leukemia was also estimated (antileukemic activity). RESULTS: A compound having p-N,N-bis(2-chloroethyl)aminophenyl-acetate as the alkylator and two ketone groups in the steroidal part demonstrated the highest statistically significant enhancement of sister chromatid exchanges and suppression of proliferation rate indices, and also caused significant antineoplastic activity. The other compounds proved less active. CONCLUSION: These results suggest that cytogenetic and antileukemic activity of alkylating steroidal esters depends on the configuration of the whole molecule and the appropriate combination of the alkylator with the steroidal molecule.

Intramyocardial injection of low-dose basic fibroblast growth factor or vascular endothelial growth factor induces angiogenesis in the infarcted rabbit myocardium.

BACKGROUND: Myocardial angiogenesis after the systemic administration of basic fibroblast growth factor or vascular endothelial growth factor at high therapeutic doses has been implicated in the occurrence of side effects that may undermine their safety. The aim of this study was to investigate the angiogenic effects of the intramyocardial administration of recombinant human basic fibroblast growth factor or vascular endothelial growth factor protein, at low doses, in the infarcted rabbit myocardium. METHODS AND RESULTS: Twenty-five New Zealand White rabbits were divided into five groups (n=5) and subjected to coronary artery ligation after lateral thoracotomy, inducing acute myocardial infarction. Five minutes later, the following substances were injected intramyocardially into the infarcted area: (a) normal saline (controls); (b) 6.25 or 12.5 mug of recombinant human basic fibroblast growth factor protein (basic fibroblast growth factor-1 group or basic fibroblast growth factor-2 group); or (c) 5 or 10 microg of recombinant human vascular endothelial growth factor 165 protein (vascular endothelial growth factor-1 group or vascular endothelial growth factor-2 group). On the 21st postoperative day, the animals were euthanized, and their hearts were subjected to histopathological examination and immunohistochemical assessment of vascular density in the infarcted area. The alkaline phosphatase anti-alkaline phosphatase procedure and the primary monoclonal antibody JC70 were used. Histopathological examination confirmed the induction of myocardial infarction. Vascular density was significantly increased (P<.004) in all treatment groups (in mean+/-S.E. vessels/x 200 optical field: basic fibroblast growth factor-1: 85.8+/-10.9; basic fibroblast growth factor-2: 76.6+/-3.7; vascular endothelial growth factor-1: 73.4+/-3.2; vascular endothelial growth factor-2: 89.5+/-5.2) compared to that in controls (58.9+/-4.9 vessels/x 200 optical field). Vascular density in the vascular endothelial growth factor-2 group was significantly higher than that in the vascular endothelial growth factor-1 group (P<.001). CONCLUSIONS: Low doses of recombinant human basic fibroblast growth factor or vascular endothelial growth factor protein, when administered intramyocardially, stimulate angiogenesis in the infarcted myocardium.

The angiogenetic effect of intramuscular administration of b-FGF and a-FGF on cardiac muscle: the influence of exercise on muscle angiogenesis.

Although angiogenetic therapy using recombinant growth factors holds much hope for the treatment of ischaemic diseases, there are still many unanswered questions, including the method of administration, the correct dose of these factors, and the duration of the therapeutic approach. Exercise has also been suggested to induce neovascularizaiton in muscles. We evaluated the angiogenetic effects of the intramuscular administration of basic-fibroblast growth factor (b-FGF) and acidic-fibroblast growth factor (a-FGF) in rat heart, compared with rats who exercised daily. In conclusion, both the intramuscular administration of b-FGF and exercise increased significantly angiogenesis in the heart in contrast to the intramuscular administration of a-FGF, which was ineffective.

NSC 290205-based therapy in murine pancreatic adenocarcinoma PAN02 in combination with adriamycin (ADR).

BACKGROUND: NSC 290205 (A) is a hybrid synthetic antitumor ester, which combines a D-lactam derivative of androsterone and nitrogen mustard. In this study, the antitumor activity of A in combination with ADR (AHOP) was investigated in comparison with the standard CHOP regimen. MATERIALS AND METHODS: PAN02 adenocarcinoma was used in this study. C57Bl mice were used for chemotherapy evaluation. The activity was assessed from the inhibition of tumor growth and the oncostatic parameter T/C%. RESULTS: Treatment with A or cyclophosphamide produced almost equal borderline activity. Moreover, both the CHOP and AHOP regimens showed significant and comparable antitumor effects. AHOP caused the maximum effect, inhibiting tumor growth by 56.8%. CHOP was less effective, producing 47.7% tumor inhibition. CONCLUSION: It is very likely that the D-lactamic steroid (androstan) alkylator forA, containing the amide group -NH-CO-, combined with ADR which intercalates between DNA base-pairs, is the explanation for the higher activity of AHOP as compared to CHOP.

The angiogenetic effect of intramuscular administration of VEGF on muscle. The influence of exercise on angiogenesis.

UNLABELLED: Although angiogenetic therapy using recombinant growth factors holds much hope for the treatment of ischemic diseases, there are still unanswered questions including the method, doses or duration of therapeutic approach. We evaluated the angiogenetic effects of vascular endothelial growth factor (VEGF) on rat heart and gastrocnemius muscles when this was administered intramuscularly and compared them to those obtained from rats, which exercised daily. CONCLUSION: Both daily swimming exercise and intramuscular administration of VEGF increased angiogenesis in rat heart, even though exercise alone was the only one that increased angiogenesis quite significantly. The combined protocol (administration of growth factor and exercise) led to an increase of angiogenesis in cardiac muscles. In contrast, there was no effect on the lateral gastrocnemius muscle either by VEGF or exercise, whereas these together induced angiogenesis locally at the site of injection.