Marek Szymański

Betulinic acid decreases expression of bcl-2 and cyclin D1, inhibits proliferation, migration and induces apoptosis in cancer cells

Betulinic acid (BA) is a pentacyclic triterpene found in many plant species, among others in the bark of white birch Betula alba. BA was reported to display a wide range of biological effects, including antiviral, antiparasitic, antibacterial and anti-inflammatory activities, and in particular to inhibit growth of cancer cells. The aim of the study was further in vitro characterization of BA anticancer activity. In this study, we demonstrated a remarkable antiproliferative effect of BA in all tested tumor cell cultures including neuroblastoma, rabdomyosarcoma-medulloblastoma, glioma, thyroid, breast, lung and colon carcinoma, leukemia and multiple myeloma, as well as in primary cultures isolated from ovarian carcinoma, cervical carcinoma and glioblastoma multiforme. Furthermore, we have shown that BA decreased cancer cell motility and induced apoptotic cell death. We also observed decrease of bcl2 and cyclin D1 genes expression, and increase of bax gene expression after betulinic acid treatment. These findings demonstrate the anticancer potential of betulinic acid and suggest that it may be taken into account as a supportive agent in the treatment of cancers with different tissue origin.

Zinc and Iron Concentration and SOD Activity in Human Semen and Seminal Plasma

The aim of the present study was to measure zinc (Zn) and iron (Fe) concentration in human semen and superoxide dismutase (SOD) activity in seminal plasma and correlate the results with sperm quality. Semen samples were obtained from men (N = 168) undergoing routine infertility evaluation. The study design included two groups based on the ejaculate parameters. Group I (n = 39) consisted of males with normal ejaculate (normozoospermia), and group II (n = 129) consisted of males with pathological spermiogram. Seminal Zn and Fe were measured in 162 samples (group I, n = 38; group II, n = 124) and SOD activity in 149 samples (group I, n = 37; group II, n = 112). Correlations were found between SOD activity and Fe and Zn concentration, and between Fe and Zn concentration. SOD activity was negatively associated with volume of semen and positively associated with rapid progressive motility, nonprogressive motility, and concentration. Negative correlation was stated between Fe concentration and normal morphology. Mean SOD activity in seminal plasma of semen from men of group I was higher than in seminal plasma of semen from men of group II. Fe concentration was higher in teratozoospermic males than in males with normal morphology of spermatozoa in group II. Our results suggest that Fe may influence spermatozoa morphology.

Betulin Elicits Anti‐Cancer Effects in Tumour Primary Cultures and Cell Lines In Vitro

Betulin is a pentacyclic triterpene found in many plant species, among others, in white birch bark. The aim of the study was in vitro characterization of the anticancer activity of betulin in a range of human tumour cell lines (neuroblastoma, rhabdomyosarcoma-medulloblastoma, glioma, thyroid, breast, lung and colon carcinoma, leukaemia and multiple myeloma), and in primary tumour cultures isolated from patients (ovarian carcinoma, cervical carcinoma and glioblastoma multiforme). In this study, we demonstrated a remarkable anti-proliferative effect of betulin in all tested tumour cell cultures. Neuroblastoma (SK-N-AS) and colon carcinoma (HT-29) were the most sensitive to the anti-proliferative effect of betulin. Furthermore, betulin altered tumour cells morphology, decreased their motility and induced apoptotic cell death. These findings demonstrate the anti-cancer potential of betulin and suggest that they may be applied as an adjunctive measure in cancer treatment.

Elevation of sE-Selectin Levels 2–24 Months following Gestational Diabetes Is Associated with Early Cardiometabolic Risk in Nondiabetic Women

Objective. We hypothesised that the endothelial dysfunction is associated with early glucose dysregulation and/or atherosclerosis risk factors in nondiabetic women with a previous history of gestational diabetes (pGDM). Material/Methods. Anthropometric parameters, glucose regulation (OGTT), insulin resistance (HOMA), lipids, biomarkers of endothelial dysfunction, and inflammation were evaluated in 85 women with pGDM and in 40 controls 2–24 months postpartum. Results. The pGDM group consisted of 67% normoglycemic women (pGDM-N) and 33% with prediabetic state (pGDM-P). The BMI, waist circumference, fasting and 2 h glucose (OGTT), soluble adhesion molecules, tissue plasminogen activator antigen, high sensitivity C-reactive protein, total-, LDL-cholesterol, and triglycerides/HDL-cholesterol ratio were higher in the pGDM women compared with the controls. After adjustment for BMI and fasting glucose, only higher triglycerides, higher TG/HDL and lower HDL-cholesterol were associated with pGDM. The pGDM-P differed from pGDM-N for only higher triglycerides and TG/HDL. The plasma level of sE-selectin was not independently associated with glucose concentration in pGDM group. sE-selectin level correlated with triglycerides, TG/HDL, plasminogen activator inhibitor-1 antigen, and sICAM-1. Conclusions. sE-selectin level correlated with components of metabolic syndrome, but only the atherogenic lipid profile was independently associated with a previous history of GDM in nondiabetic women 2–24 months postpartum.

The employment of IVF techniques for establishment of sodium, copper and selenium impact upon human sperm quality

We analysed sodium (Na), copper (Cu) and selenium (Se) levels in human semen and glutathione peroxidase activity (GPx) in seminal plasma and examined their relationships with sperm quality. Semen samples were obtained from men (n=168) undergoing routine infertility evaluation. The study design included two groups based on standard ejaculate parameters: Group I (n=39) with normal ejaculates (normozoospermia) and Group II (n=129) with a pathological spermiogram. Se concentration (but not Na or Cu) and GPx activity were significantly higher in normozoospermic males than in those with a pathological spermiogram and also in males with correct sperm motility and normal sperm morphology than in asthenozoospermic and teratozoospermic males. There were significant correlations between sperm motility, Se and GPx, between rapid progressive motility and Cu, between sperm motility and Na, between normal sperm morphology and Se and Cu and between sperm concentration and Cu and GPx. Significant correlations were found between Na and Cu, between Na and Se and between Cu and Se in human semen in relation to alcohol consumption and tobacco use. Na, Cu, Se and GPx are related to sperm characteristics and male fertility and their survey could improve male infertility diagnosis.

Procoagulants and anticoagulants in fetal blood. A literature survey.

In intrauterine life, hemostasis is maintained by the same components as in extrauterine life (blood platelets, coagulation and fibrinolysis systems, involvement of the vascular wall); in the fetus, however, these components show significant differences of a quantitative/qualitative nature. In the present study, we surveyed the literature on the coagulation system in the fetus. We focused on the velocity of development of the coagulation system, being reflected in the increased concentration of all procoagulants and anticoagulants (a rise from approximately 20% in the middle of pregnancy to about 60% or more in the period of labor; exceptions: factors V, VIII and XIII which in the labor period reach the adult level) and screening test results (prothrombin time, aPTT - activated prothrombin time, and thrombin time). Reference values were given for the 19-38 weeks of pregnancy and the labor term. Biochemical features of fetal fibrinogen and PIVKA factors were also discussed. The role of activated protein C (APC) in the maintenance of balance between procoagulants and anticoagulants was postulated as well as the role of APC in the formation of thrombin activatable fibrinolysis inhibitor (TAFI).

A comparative study of the protein C system in mother's blood, cord blood and amniotic fluid

Activated protein C (APC) is an important anticoagulant which plays a role in pathophysiology of pregnancy, e.g. in maintenance of the uteroplacental circulation and development of the fetus as well as in pathogenesis of preeclampsia. The study objective was to compare the levels of the respective components of the protein C system (protein C, PC; protein S, PS; thrombomodulin, TM) as well as thrombin activatable fibrinolysis inhibitor - TAFI in mothers blood, cord blood and amniotic fluid. The study group consisted of 136 healthy parturients at term, divided into subgroups of 30-35. The immunoenzymatic method (ELISA) was used to measure the antigens of the components studied. The concentrations of PC and PS antigens were the highest in the mothers blood plasma (135.11+/-1.05% and 92.0+/-13.24%, respectively), lower in cord blood plasma (57.60+/-10.32% and 33.19+/-4.96%, respectively) and the lowest in amniotic fluid (6.75+/-3.50% and 2.40+/-1.64%, respectively); the differences between the levels of that of mother, fetus and amniotic fluid were statistically significant (p< or =0.0001). The TM and TAFI antigen concentrations were the highest in cord blood plasma (11.35+/-3.71 ng/ml and 91.50 (median; range: 71.76-160.77) ng/ml, respectively) and lower in maternal plasma (4.51+/-0.71 ng/ml and 55.46 - median; range: 39.77-68.54 ng/ml, respectively); the differences between the levels of that of cord blood plasma and maternal plasma were statistically significant (p< or =0.0001). Of the three protein C system components, PC and PS occur in relatively high concentrations in maternal blood, being lower in fetal blood and the lowest in amniotic fluid. On the other hand, as an exception, the concentrations of TM and TAFI are the highest in fetus blood.

Differentiating between benign and malignant adnexal lesions with contrast‐enhanced transvaginal ultrasonography

To analyze the relationship between contrast kinetics in tumorous vessels and lesion histologic type in an attempt to differentiate between malignant and benign disease.

“Benefit” of Routine Ovarian Biopsy during Laparotomy for Diseases of the Female Reproductive Organs.

Background: Ovarian cancer is the most common cause of death among patients diagnosed with reproductive organ cancers in Poland. Despite the progress and continual improvements in diagnostic techniques and methods of cancer treatment, the epidemiology and natural history of ovarian cancer remain largely unchanged. Approximately three quarters of ovarian carcinoma cases are not detected or treated until the third or fourth stage of the disease. The current routine diagnostic procedures include ultrasound examination, biochemistry marker assessments and histopathological evaluations of ovarian tissue to confirm a diagnosis. The preoperative diagnosis of ovarian cancer remains unsatisfactory, and the search for new effective methods has not provided satisfactory results.Objectives: To determine whether routine biopsy of macroscopically unchanged ovaries provides sufficient benefit.Material and methods: We conducted a clinical trial involving approximately 1,000 ovaries from which tissue samples were collected during reproductive organ surgeries, and the tissues were examined by a pathologist. Spearman’s rank correlation was used to compare the results statistically.Results: The results of the histopathological evaluation of macroscopically unchanged ovaries were normal in 99.8% of patients.Conclusion: In this context, routine biopsy of macroscopically unchanged ovaries does not provide sufficient benefit. Moreover, it may be associated with increases in surgical complications such as bleeding from the biopsy site. Therefore, biopsy of the ovaries during surgery of reproductive organs should not be performed routinely unless cancer is suspected.

Human Sperm Characteristics with Regard to Cobalt, Chromium, and Lead in Semen and Activity of Catalase in Seminal Plasma

We analyzed cobalt (Co), chromium (Cr), and lead (Pb) concentrations in human semen and catalase CAT activity in seminal plasma and the effects of their relations on the sperm quality. We obtained semen samples from men (n = 168) undergoing routine infertility evaluation. Studies included two groups based on the ejaculate parameters: I (n = 39; normal ejaculate; normozoospermia); II (n = 129; pathological spermiogram). We examined relationships and differences between Co, Cr, and Pb concentrations in seminal plasma, CAT activity, and semen parameters. We did not establish differences in Co, Cr, and Pb concentrations and CAT activity from men between normozoospermic and those with pathological spermiogram. We found a significantly lower Co concentration and CAT activity in males with normal sperm motility than in asthenozoospermic males. We found significantly lower Co and a higher Pb concentration in males with normal morphology of spermatozoa than in teratozoospermic males. We found a significantly higher Pb concentration in the individuals with consumption of alcohol than in those without consumption. There were significant correlations between Co and Pb concentrations, sperm progressive motility (A + B, i.e., fast and slow progressive motility; Co—negatively; Pb—positively), and normal morphology of spermatozoa (Co—negatively; Pb—positively). We found a significant negative correlation between Cr concentration and slow progressive motility, and between CAT activity and volume of ejaculate. Co, Cr, and Pb levels and CAT activity were related to sperm characteristics and male fertility. The impact of alcohol may be manifested by a disturbance in Pb equilibrium in the body. Co and Pb influence progressive motility and normal morphology of human spermatozoa. Thus, Co and Pb levels in semen may be a useful diagnostic in male infertility. Most of the results of this study are in contrast to expectations. Namely, Pb is a toxic element and its harmful effects (poor semen quality) may be expected already at relatively low level of Pb exposure and are particularly visible with increasing of Pb. Co and Cr(III) are essential elements and harmful effects may be expected at their deficiency and/or overexposure.