Relationships between CD34-, CD105- and bcl-2-Expression Levels and Contrast-Enhanced Ultrasound-Based Differential Diagnosis of Adnexal Tumours.

The relationships between CEUS parameters of adnexal tumours and postoperative immunohistochemical assessments of CD34, CD105 and bcl-2 were analysed. This study aimed to investigate whether contrast-enhanced ultrasonography (CEUS) parameters depend on the microvascular density of the tumour lesion found after surgery. Fifty-one patients with a diagnosis of adnexal tumours were included in this single-centre, prospective study. Participants underwent preoperative CEUS (contrast-enhanced ultrasound). Colour Doppler enhancement characterisation parameters (Ystart, Ymax and S) were determined. Immunohistochemical examination of histological specimens of the adnexal lesions was then carried out to determine the expression levels of the CD34, CD105 and bcl-2 proteins. Relationships between the aforementioned parameters were investigated. No significant statistical correlations were observed between CD34, CD105 and bcl2 expression levels and CEUS parameters, independently of whether the operated lesion was malignant or benign. Transvaginal CEUS is diagnostic for the detection of pathological neoplastic vascularisation of an adnexal lesion independent of the density of microcapillaries found postoperatively.

External and Genetic Conditions Determining Male Infertility.

We explain environmental and genetic factors determining male genetic conditions and infertility and evaluate the significance of environmental stressors in shaping defensive responses, which is used in the diagnosis and treatment of male infertility. This is done through the impact of external and internal stressors and their instability on sperm parameters and their contribution to immunogenetic disorders and hazardous DNA mutations. As chemical compounds and physical factors play an important role in the induction of immunogenetic disorders and affect the activity of enzymatic and non-enzymatic responses, causing oxidative stress, and leading to apoptosis, they downgrade semen quality. These factors are closely connected with male reproductive potential since genetic polymorphisms and mutations in chromosomes 7, X, and Y critically impact on spermatogenesis. Microdeletions in the Azoospermic Factor AZF region directly cause defective sperm production. Among mutations in chromosome 7, impairments in the cystic fibrosis transmembrane conductance regulator CFTR gene are destructive for fertility in cystic fibrosis, when spermatic ducts undergo complete obstruction. This problem was not previously analyzed in such a form. Alongside karyotype abnormalities AZF microdeletions are the reason of spermatogenic failure. Amongst AZF genes, the deleted in azoospermia DAZ gene family is reported as most frequently deleted AZF. Screening of AZF microdeletions is useful in explaining idiopathic cases of male infertility as well as in genetic consulting prior to assisted reproduction. Based on the current state of research we answer the following questions: (1) How do environmental stressors lessen the quality of sperm and reduce male fertility; (2) which chemical elements induce oxidative stress and immunogenetic changes in the male reproductive system; (3) how do polymorphisms correlate with changes in reproductive potential and pro-antioxidative mechanisms as markers of pathophysiological disturbances of the male reproductive condition; (4) how do environmental stressors of immunogenetic disorders accompany male infertility and responses; and (5) what is the distribution and prevalence of environmental and genetic risk factors.

Mechanochemical Encapsulation of Fullerenes in Peptidic Containers Prepared by Dynamic Chiral Self-Sorting and Self-Assembly.

Molecular capsules composed of amino acid or peptide derivatives connected to resorcin[4]arene scaffolds through acylhydrazone linkers have been synthesized using dynamic covalent chemistry (DCC) and hydrogen-bond-based self-assembly. The dynamic character of the linkers and the preference of the peptides towards self-assembly into ß-barrel-type motifs lead to the spontaneous amplification of formation of homochiral capsules from mixtures of different substrates. The capsules have cavities of around 800 Å(3) and exhibit good kinetic stability. Although they retain their dynamic character, which allows processes such as chiral self-sorting and chiral self-assembly to operate with high fidelity, guest complexation is hindered in solution. However, the quantitative complexation of even very large guests, such as fullerene C60 or C70 , is possible through the utilization of reversible covalent bonds or the application of mechanochemical methods. The NMR spectra show the influence of the chiral environment on the symmetry of the fullerene molecules, which results in the differentiation of diastereotopic carbon atoms for C70 , and the X-ray structures provide unique information on the modes of peptide-fullerene interactions.

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

OBJECTIVE: To analyze the relationship between contrast kinetics in tumorous vessels and lesion histologic type in an attempt to differentiate between malignant and benign disease. METHODS: In a single-center prospective study, patients who had been referred for elective surgery because of a diagnosis of unilateral and/or bilateral adnexal masses were enrolled at Dr Jan Biziel University Hospital, Bydgoszcz, Poland, between January 2012 and September 2013. Participants underwent contrast-enhanced ultrasonography examination (CEUS). Contrast kinetics were obtained and compared with the neovascularization of the tumor. Accuracy, and positive and negative predictive values were calculated. RESULTS: Among 160 enrolled patients, 84 underwent CEUS examination and 51 lesions were studied. Baseline and maximum color Doppler intensities were significantly higher in malignant than in benign tumors (P < 0.001 for both). Similarly, the absolute and relative increases in color Doppler intensity were significantly higher in malignant tumors (P < 0.001). The estimated positive predictive value was 97.1%, the negative predictive value was 100%, and the accuracy was 100%. Peak enhanced intensity of fractional color Doppler Area and area under the time-intensity curve (S-parameter) correlated significantly with the histology of the lesion (P < 0.001). Probability curves demonstrated that higher S-parameter values were correlated with a higher risk of malignancy. CONCLUSION: Transvaginal CEUS is a reliable and reproducible way to differentiate between benign and malignant adnexal lesions.

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.

Determination of Rare Earth Elements in Human Sperm and Association with Semen Quality.

The aim of the present study was to measure lanthanum (La), cerium (Ce), europium (Eu), and gadolinium (Gd) concentrations in human semen and correlate the results with sperm quality. The median semen content of La was 19.5 µg kg(-1) dry weight (dw) (range 2.27-269), of Ce was 41.9 µg kg(-1) dw (range 4.52 to 167), of Eu was 0.68 µg kg(-1) dw (range 0.06-1.95), of Gd was 3.19 µg kg(-1) dw (range 0.38-12.0), and of calcium (Ca) was 4063 mg kg(-1) dw (range 484-17,191). Concentrations of La, Ce, Eu, Gd, and Ca were significantly lower in nondrinkers' semen than in semen from drinkers. Significant differences were detected between La, Ce, Eu, Gd, and Ca concentrations in semen from nondrinkers and moderate drinkers. Concentrations of La, Ce, and Gd in semen of short-term smokers were significantly lower than those in extremely long-term smokers. Significant differences were also detected between La concentration in semen from a group of short-term smokers and that of a group of long-term smokers. Positive correlations were found between La, Ce, Eu, Gd, and Ca concentrations in semen. La, Ce, Gd, and Ca concentrations in semen were positively associated with progressive motility and percentage of normal spermatozoa. Positive correlations were found between Ca and sperm concentration. Concentrations of La, Ce, and Gd were negatively associated with sperm concentration, whilst Ca concentration was negatively associated with volume of ejaculate. At the examined level, La, Ce, Eu, and Gd did not affect sperm quality, whereas alcohol consumption and smoking might have increased the level of rare earth elements in semen.

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.

[Retrospective analysis of ocular disorders and frequency of cesarean sections for ocular indications in 2000-2008--our own experience]. / Retrospektywna analiza patolog i narz du wzroku i czestosci ciec cesarskich ze wskazan okulistycznych w latach 2000-2008 w materiale wlasnym.

UNLABELLED: 1. Evaluation of frequency of cesarean sections for ocular indications. 2. Analysis of ophthalmological disorders as indications for cesarean section. MATERIAL AND METHODS: 4895 cesarean sections were performed (100 due to ocular indications) in the Department of Obstetrics, Female Pathology and Oncological Gynecology between 2000 and 2008. Medical documentation was analyzed. RESULTS: Among 4895 patients undergoing cesarean sections, 100 (2.04%) presented a written certification from an ophthalmologist suggesting this way of delivery. The frequency of c-sections due to ocular indications continued to increase between 2000-2005 and has been in decline since 2006. The most common ophthalmological disorders included myopia (57%), retinopathy (20%), glaucoma (5%), imminent retinal detachment (4%) and past retinal detachment (3%). In 45% of patients an eye pathology was the only reason for a cesarean section. CONCLUSION: 1. The frequency of cesarean sections due to ocular reasons in our material was 0.7%- 3.44%, average 2.04%. 2. Since 2006 the number of ocular indications for cesarean section has been decreasing. Nevertheless, it remains to be twice as high as in 2000. 3. The most common eye disorders leading to cesarean section were myopia and retinopathy 4. In almost half of the patients the decision to conduct a cesarean section was based solely on ophthalmological indications.

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.

Opioid-binding protein/cell adhesion molecule-like (OPCML) gene and promoter methylation status in women with ovarian cancer.

OBJECTIVE: The expression profile of the OPMCL gene was studied to find out if there was any evidence of a CpG island methylator phenotype and if there was an association of CpG island methylation with the gene downregulation in women with ovarian cancer. MATERIAL AND METHODS: Expression of OPCML in 43 ovarian cancer tumor samples and in 4 normal ovaries was determined by RT-PCR. Methylation status of OPCML promoter region was studied with methylation-specific PCR (MSP) method. Possible associations with selected clinicopathologic variables: FIGO stage, histological grade, patient's age and menopausal status were tested. RESULTS: In all normal ovarian samples OPCML mRNA was present, but it was not detectable in 24 of 43 ovarian cancer cases. We have not found the relationship between age and menopausal status with the presence of RTPCR product of OPCML. Hypermethylation of OPCML was not correlated to FIGO stage, however, in 80% of cases with methylated OPCML early clinical stage was also present. Tumor grading and histological type had no significant influence on the presence of hypermethylation of OPCML gene. In 20 of 43 cases of ovarian cancer methylated product of MSP amplification was present. In a group of OPCMLmRNA-negative tumors there were 75% of cases with hypermethylated exon of OPCML and the correlation between these variables was statistically significant (chi2 =17.7; p=0,00003). No promoter hypermethylation of the studied gene was found in normal ovaries. CONCLUSIONS: Reduced OPCMPL gene expression in ovarian cancer in comparison to normal ovaries could be related to the hypermethylation of promoter region. This epigenetic alteration may be the reason of gene silencing and the loss of suppressor function.

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.

[The effects androgen therapy on smoking and non-smoking patients with erectile dysfunction in andropausal syndrome]. / Efekty terapii androgenowej u pacjentów palacych i niepalacych z zaburzeniami erekcji w zespole andropauzalnym.

The effects of the testosterone therapy were examined in two groups of man who demonstrated erectile dysfunction in andropausal syndrome. An increase of sexual function in both groups has been observed. In the smoking group the results were lower than in the non-smoking.

[Influence of cigarette smoking on some sperm parameters in males with decreased fertility]. / Wplyw palenia tytoniu na niektóre parametry nasienia u mezczyzn o obnizonej plodnosci.

112 patients from infertile couples with diagnosed asthenospermia and oligoasthenospermia have been examined. The results have been analysed in view of smoking. An increased number of antisperm antibodies have been detected in smoking patients. No difference between the two groups examined according to WHO standards have been found.

[Symptoms of andropausal syndrome in smoking and non-smoking males]. / Wystepowanie objawów zespolu andropauzalnego wsród palacych i niepalacych.

Symptoms of andropause syndrome such as: erectile dysfunction, somatovegetative and psychic symptoms have been examined in groups of smoking and non-smoking patients between 45 and 75 years of age Tests of testosterone, prolactin and SHBG levels have been carried out. Earlier andropause, a lower level of testosterone as well as more common arterial hypertension have been found in the group of smoking patients.

[Color Doppler blood flow measurements and microvessel density assessment in ovarian tumors]. / Ocena angiogenezy nowotworowej w guzach jajnika przy wykorzystaniu ultrasonografii z kolorowym Dopplerem oraz immunohistochemicznego badania gestosci mikrokapilar.

OBJECTIVE: The aim of our study was to compare ultrasound vascular blood flow indices with the expression of CD-34 in women with benign and malignant adnexal tumors. MATERIALS AND METHODS: Transvaginal color and pulsed Doppler sonography was performed before surgical procedure in 105 women with adnexal tumors. Blood flow indices: pulsatility index (PI) and resistive index (RI) in blood vessels with the highest flow velocity were measured within each tumor. Immunohistochemical analysis of microvessel density (MVD) was performed on representative highly vascular tumor specimens fixed in 10% formalin and paraffin embedded. The primary monoclonal mouse anti-human CD-34 antibody (1:25, DAKO, Denmark) was used. Statistical calculations included group comparison with Kruskal-Wallis ANOVA on ranks and correlation analysis (Statistica for Windows 6.0, Statsoft Poland). RESULTS: Mean age of the studied women was 55.6 +/- 11.5 yrs. Of 104 tumors, 35 (33.6%) were benign and 69 (66.4%) were malignant. The latter included 14 FIGO stage I cases. Low resistance or pulsatility indices (RI < 0.5 or PI < 0.8) were found in 58 of 69 (84%) malignant masses and in 21 of 35 (60%) benign tumors. Substantial overlap in measured indices was found between both studied groups. Median number of microvessels per high power field in the benign and malignant tumors were 37 (range: 14-156) and 68 (range: 25-177), respectively. These differences were statistically significant (p = 0.007, Mann-Whitney U test). Also, a significant correlation was found between MVD and low resistance to blood flow as measured by the PI or RI (r = 0.43, p < 0.05). However, no statistically significant differences in MVD were found between FIGO stage I and other stages of ovarian cancer. CONCLUSION: Low resistance to blood flow as measured by the resistive or pulsatlity indices used in color Doppler sonography may by positively correlated with the microvessel density in the malignant ovarian tumors.

[Neo-angiogenesis in immunohistochemical techniques as a prognostic factor in endometrial carcinoma]. / Immunohistochemiczna ocena neoangiogenezy jako elementu rokowniczego w raku endometrium.

OBJECTIVE: Angiogenesis in malignant tumors is a prognostic factor associated with tumor growth and metastasis. The aim of the research was: determination of the angiodensity rate in two immunohistochemical techniques, estimation of the value of the examined parameter at different stages of clinical progression and histological differentiation of endometrial carcinoma, and analysis of the obtained values as prognostic factors in the disease process. MATERIALS AND METHODS: The examination covered 86 women treated surgically for endometrial carcinoma. The preliminary histological evaluation was followed by immunohistochemical methods. The microvessels within the invasive cancer were highlighted by means of immuno-cytochemical staining to detect CD-31 and CD-105 antigen. The average value of angiodesity was estimated by means of a computer image analyser. RESULTS: The group of patients at the preinvasive stage of the disease manifested significantly statistically lower values of angiodensity. It was detected that the histological differentiation of carcinoma does not influence intensification of angiogenesis. Higher values of this parameter have an adverse influence on the survival rate. CONCLUSION: The evaluation of the angiodensity coefficient can be a helpful prognostic parameter in endometrial carcinoma.

[Microvessel density index as a prognostic factor in a low histological differentiation stage of endometrial carcinoma]. / Przydatnosc oznaczania gestosci naczyniowej jako czynnika rokowniczego w rakach trzonu macicy o niskim stopniu zróznicowania.

OBJECTIVE: Angiogenesis in malignant tumors is a prognostic factor associated with tumor growth and metastasis. Studies of angiogenesis in breast, prostate and lung cancer showed that neovascularisation correlates with likelihood of metastasis and recurrence. Our study was to evaluate microvessel density as a prognostic factor in endometrial cancer. METHODS: Between 1995-1999, 58 women were treated for endometrial carcinoma. The primary treatment consisted of total abdominal hysterectomy, bilateral salpingoophorectomy and pelvic lymphadenectomy. The microscopic examination of paraffin blocks showed the areas of the deepest myometrial invasion. The microvessels within the invasive cancer were highlighted by means of immuno-cytochemical staining to detect CD-31 antigen. RESULTS: Microvessel count was related to likelihood of recurrence. We found statistically significant differences between patients who died after operation and patients with nonrecurrence process. All patients were in the same stage and grade of endometrial carcinoma. CONCLUSION: Microvessel density index seems to be an important factor for planing postoperation treatment in endometrial carcinoma.

[Evaluation of selected risk factors in patients operated for uterine body carcinoma]. / Ocena wybranych czynników rokowniczych u kobiet operowanych z powodu raka trzonu macicy.

OBJECTIVES: Uterus body carcinoma ranks among to the most common malignant neoplasms. It is of special interest what kind of factor influences on the survival span of treated patients. DESIGN: Evaluation of selected risk factors such as: age, obesity, clinical stage, type and histologic differentiation and proliferation depths on the 5-year survival span. MATERIALS AND METHODS: /Due to our research we analyzed 280 endometrium samples of patients with the diagnosis of endometrial cancer, who*.../ Analysis was made on the group of 280 endometrium carcinoma patients, who were operated in the Department of Obstetrics and Women Diseases, University School of Medicine in Bydgoszcz in 1982-2000 period, 221 of the total number of patients (78.8%) were in the cancer stage I, while 33 (11.9%) in stage II, followed by 26 (9.3%) in stage III. RESULTS: The highest percentage of 5-year survival time was observed in the group of patients under age of 50. In patients with the clinical stage I and proliferation depths under 1/2 of myometrum the percentage of 5-year survival time was 91%. Adenocarcinoma was the most common type of cancer and also with the best prognosis (81% of 5-year survival). Neither histologic differentiation G1 nor G2 have an influence on the survival time of operated patients. CONCLUSIONS: 1. The proliferation depths, histologic type of the endometrial carcinoma and clinical stage are the major prognostic factors for the uterus body carcinoma. 2. Endometrial carcinoma in the group of patients under age of 50 is connected with the higher percentage of five-year survival time.