Nematodes As Soil Stress Indicators for Polycyclic Aromatic Hydrocarbons: a Review.

Polycyclic aromatic hydrocarbons (PAHs) are an important group of organic pollutants present in all parts of the environment, affecting ecosystems and human health. PAHs, which have a strong affinity for organic carbon, are found in large quantities in soil, which is one of the most important sinks for these contaminants. Their impact on the soil biotic compartments depends on a number of different factors in combination with PAH behaviour and can be assessed using soil monitoring. Soil fauna have already shown excellent properties for biomonitoring of contaminants with most promising indicator frameworks based on nematodes, which are involved in essential processes in this environment. Nematodes respond to PAHs at multiple levels, including molecular, individual and community levels. At the molecular level, this is associated with activation of metabolic pathways for xenobiotics and increased demand for energy and resources. At the individual level, this is reflected in the slowing down of various physiological processes, which has consequences at the individual and community level for sensitive taxa. In this review, the toxicity and the direct and indirect effects of PAHs on soil nematode communities are discussed. It also considers the perspectives and challenges in assessing the toxicity of PAHs and their indication using soil nematodes.

Ultrastructure and Cytochemistry of the Mature Spermatozoon of Khawia Armeniaca (Cholodkovsky, 1915) (Caryophyllidea: Lytocestidae), a Parasite of Capoeta Capoeta Sevangi (De Filippi, 1865) (Teleostei, Cyprinidae).

The mature spermatozoon of Khawia armeniaca, a monozoic caryophyllidean parasite of templar fish Capoeta capoeta sevangi (De Filippi, 1865) from the Lake Sevan, Armenia, has been studied using transmission electron microscopy and cytochemical technique of Thiéry (1967) for the first time. The mature spermatozoon of K. armeniaca consists of a single axoneme with the 9+'1' trepaxonematan structure, cortical microtubules and nucleus which are situated parallel to the longitudinal axis of the spermatozoon, and a moderately electrondense cytoplasm with glycogen particles. The cortical microtubules are arranged in one continuous semicircle beneath the plasma membrane in Region II and anterior part of Region III of the mature spermatozoon. The two opposite rows of cortical microtubules are observed in the remaining nuclear and at the beginning of the postnuclear part (Regions III, IV) of the male gamete The number of cortical microtubules is remarkably variable in the spermatozoa of various Khawia species. K. armeniaca exhibits the highest number of cortical microtubules in comparison with K. sinensis and K. rossittensis. Glycogen was detected in the cytoplasm of prenuclear (II), nuclear (III) and postnuclear (IV) regions with different ultrastructural organization of the mature spermatozoon of K. armeniaca. Variations of sperm ultrastructural characters within caryophyllideans and other cestodes are discussed.

A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy.

BACKGROUND: This phase II study was conducted to assess clinical efficacy of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer not progressing during first-line docetaxel-based therapy. PATIENTS AND METHODS: Patients were randomly assigned (1 : 1) to receive tasquinimod (0.25-1.0 mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic use. Quality of life was measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and by the EuroQol-5 Dimension Quality of Life Instrument (EQ-5D). Adverse events were recorded. RESULTS: A total of 219 patients were screened and 144 patients randomized. The median duration of treatment was 18.7 weeks (range 0.6-102.7 weeks) for the tasquinimod arm and 19.2 weeks (range 0.4-80.0 weeks) for the placebo arm. Median (90% CI) rPFS was 31.7 (24.3-53.7) and 22.7 (16.1-25.9) weeks in the tasquinimod and placebo arms, respectively [HR (90% CI) 0.6 (0.4-0.9), P = 0.0162]. The median OS was not reached because only 14 deaths occurred by the cut-off date. No statistically significant differences between treatment arms were noted for symptomatic PFS, PFS 2, BPI score, FACT-P score, or EQ-5D. The incidence of any treatment emergent adverse event (TEAE) was similar in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% versus 27.1%). CONCLUSIONS: Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate-resistant prostate cancer. Maintenance tasquinimod therapy significantly reduced the risk of rPFS by 40%. CLINICALTRIALS: gov identifier NCT01732549.

[Immunotherapy of Urothelial Carcinoma of the Bladder -  from BCG Vaccines to Targeted Therapy]. / Imunoterapie uroteliálního karcinomu mocového mechýre -  od BCG vakcín k cílené imunoterapii.

Bladder cancer has high prevalence in men and women. Bladder cancer usually originates from urothelium. More than 75% of cases are classified as nonmuscle invasive bladder cancer. Urothelial bladder carcinoma is usually managed by transurethral resection of the bladder tumor. Role of transurethral resection of the bladder tumor is also essential in bladder cancer staging. Local prophylaxis is used in nonmuscle invasive bladder cancer to reduce risk of recurrence. While local chemoprophylaxis is sufficient in low and middle risk patients, intravesical instillation of Mycobacterium bovis bacillus CalmetteGuerin (BCG) is preferred in high risk bladder cancer. Chemotherapy alone or in combination with locoregional treatment is used in advanced bladder cancer. New immunotherapy modalities have proven their efficacy in several clinical studies in advanced bladder cancer.

[Prostate carcinoma. Current dilemma of urooncology. How to help the needed and not to harm the others]. / Karcinom prostaty, aktuální dilema uroonkologie. Jak prospet ohrozeným pacientum a neuskodit tem ostatním.

There is a remarkably rising incidence of histologically proven prostate cancer since the introduction of prostatic specific antigen (PSA) test into clinical practice. TNM classification of these tumors in about 50% of cases is in categories T1,2 N0M0, Gleason score 7 and PSA level under 10 ug/ l (Graph 1). Such tumors are considered low risk and therefore conservative approach seems to be acceptable therapeutic variant. In spite of nonsurgical approach, patients with the so called early stage diagnosed disease have been almost only indicated for radical prostatectomy with a therapeutic approach. More than 2,100 men underwent radical prostatectomy (RP) in the Czech Republic in 2009 but mortality curve remained unchanged for years (Graph 2). The largest study (ERSPC) looking for influence of PSA screening on mortality, involving 182,000 men, of which 162,000 were valuable for analysis, really lowered mortality. After 11 years, in the screened arm (PCA arm) mortality decreased by more than 20% in the screened arm (PCA arm) when compared with unscreened arm. But to save one life, 1,410 patients had to be screened and 48 of them underwent RP. But ERSPC results (and those similar from eg. PLCO study) gave a rise of speculation if all early detected tumors are indeed candidates for surgery (overtreatment), even if such intensive PSA screening is reasonable (overdiagnosis). In last decades, results of several studies support an opinion that low risk tumors diagnosed in men over 68 years, with several co morbidities and in less favorite health status would not be proper candidates for conservative approach (active surveillance or watchful waiting). As a consequence of these considerations, a question arises whether selected PSA test should not be more reasonable. In such a case, a patient should thoroughly discuss what profit the PSA test brings to him with his doctor.

[Application of SNP array method in prenatal diagnosis]. / Aplikace metody SNP array v prenatální diagnostice.

OBJECTIVES: SNP array (array method using Single Nucleotide Polymorphisms) enables to detect cytogenetically undetectable submicroscopic alterations (microdeletions, microduplications), which could be also causative for ultrasonographic anomalies of fetus. This article describes the principle, advantages, disadvantages and application possibilities of the SNP array method in prenatal diagnosis. The ten month experience with SNP array use in prenatal diagnosis is presented. DESIGN: Prospective study. SETTINGS: Gennet, Prague. MATERIAL AND METHODS: During the period from April 2010 to January 2011 we performed 110 SNP array analyses of fetal DNA: 14 chorionic villi samples (CVS), 88 amniotic fluid samples (AMC), 1 cord blood sample and 7 miscarriage samples. Laboratory tests were carried out on DNA from both cultured and uncultured fetal cells. Examinations were performed in fetuses with sonographic abnormal findings having normal karyotype. In addition 14 fetal cytogenetic abnormalities were solved. SNP array analysis was performed using Illumina InfiniumHD HumanCytoSNP-12 chip. All data were analysed by Illumina KaryoStudio and GenomeStudio software. RESULTS: SNP array analysis was performed in 108 fetuses (only 2 examination failures, 1.8%). In total, we detected CNV (copy number variation) in 29 samples (29/108 = 27%). 15% (16/108) of fetuses with abnormal ultrasound findings were found to carry clinically relevant CNV. Probably benign CNVs were found in 8 samples (8/108 = 7%) and in additional 5 CNVs parental samples have not been analysed yet. Excluding karyotypically abnormal cases clinically relevant CNVs were found in 10% of fetuses (9/94). In all cases with de novo chromosomal aberration the clinical relevancy was clarified (imbalances in 50%). CONCLUSION: Our data suggest that SNP array analysis is a relevant and useful technique in prenatal diagnosis.

Finasteride treatment and neuroactive steroid formation.

Finasteride is the 5alpha-reductase inhibitor that received clinical approval for the treatment of human benign prostate hyperplasia and androgenetic alopecia. The 5alpha-reductase is enzyme responsible for the reduction of testosterone to dihydrostestosterone, progesterone to dihydroprogesterone and deoxycorticosterone to dihydrodeoxycorticosterone, steroids modulating the action of gamma-aminobutyric acid on GABA receptors. These neuroactive steroids possess anticonvulsant, antidepressant and anxiolytic effects. The objective of the study was to determine the effect of finasteride therapy on a broad steroid spectrum in men with benign prostate hyperplasia. A group of 20 men with benign prostate hyperplasia was involved in the present study. Finasteride in the daily dose of 5 mg/day was administrated for 4 months. In all individuals, their hormonal profile of steroid hormones was determined before and after 4 months lasting finasteride treatment. Finasteride treatment resulted in a significant decrease all alpha-reduced and increase of most 5beta-reduced metabolites of testosterone and progesterone as well as in an increase of 7alpha-hydoxyderivatives, which are known as neuroactive steroids acting by modulation of GABAA and NMAD receptors in the brain. In the course of finasteride treatment the decrease of the concentration of circulating steroids with known inhibitory activity on GABA-ergic excitation in the brain is very probably an important factors contributing to the development of the symptoms of depression seen in some isolated cases of finasteride administration.

Hormonal homeostasis in a group of 216 aging Czech males and correlation with responses to a questionnaire of the University of St Louis.

UNLABELLED: The male aging process is accompanied by changes in the levels of several types of hormones. Falling levels of androgenic-anabolic steroids (total testosterone, free testosterone, biologically accessible testosterone, dehydroepiandrosterone) correspond to a group of symptoms referred to as PADAM syndrome (Partial Androgen Deficiency in the Aging Male). In the case of those carefully examined patients with symptoms of PADAM and proven hypogonadism, administering androgen supplements can alleviate some of the undesirable manifestations. In its literature, the University of St Louis repeatedly refers to its questionnaire as a verbal tool for the detection of possible hypogonadism. The aim of this study was to ascertain to what extent the aging process is evident in hormonal homeostasis detected in laboratory testing, and the extent to which this data is in accord with the evaluation of responses to questions in the University of St Louis questionnaire. METHOD: 216 men aged over 50 years were examined. Measurements were taken of: testosterone; the index of free testosterone; androstenedione; dihydrotestosterone; dehydroepiandrosterone and its sulfate; isomers 7alpha- and 7beta-hydroxydehydroepiandrosterone; epitestosterone; luteinizing hormone (LH); follicle-stimulating hormone (FSH); prolactin; and sexual hormone-binding globulin (SHBG). Evaluations of the patients' responses to the University of St Louis questionnaire were compared with the results of the laboratory tests. RESULTS: The study confirms that the most prominent phenomenon is that of an age-related decrease in the index of free testosterone, which is indicated in particular by an increase in the level of SHBG, and by a decrease in dehydroepiandrosterone and its derivatives. No significant correlation was found between levels of hormones and single items on the questionnaire, nor with the overall score arrived at by studying the patients' data.

[Hormones and quality of life in aging men]. / Hormony a kvalita zivota stárnoucích muzu.

BACKGROUND: Aging men suffer from a decrease of androgen-anabolic steroids known as "Partial Androgen Decline in the Aging Male" (PADAM) that is sometimes compensated by the use of androgen replacement therapy. METHODS AND RESULTS: To decide whether androgen therapy should be considered, hormonal serum levels are commonly tested. In addition, the St. Louis questionnaire is used as and indication. Accordingly, serum levels of testosterone, androstendione, dihydrotestosterone, dehydroepiandrosterone, its sulphate, epimers of 7-hydroxy-dehydroepiandrosterone, epitestosterone, lutropin, follitropin, prolactin and sex hormone binding globulin were measured in 216 men over 50 years of age. Further, the Sr. Louis questionnaire was applied and the extent of the relations among the data was evaluated. RIA and IRMA kits from Immunotech and Orion-Diagnostica were used for measurement of the hormones except epitestosterone and 7-hydroxy-dehydroepiandrosterone epimers, which were determined using specific radioimmunoassays. CONCLUSIONS: The decline in the index of free testosterone, given by the increase of SHBG levels, as well as the decrease in the levels of DHEA and its derivates were the most prominent. No correlation was found between the levels of hormones and the individual items of the questionnaire or with the total score calculated from the questionnaire data. In conclusion, the University of Saint Louis questionnaire did not give a reliable indication of an androgen deficit. However, the found values and their changes can still be helpful during the decision process concerning indication and initiation of hormone replacement.

Thermoluminescence and fluorescence study of changes in Photosystem II photochemistry in desiccating barley leaves.

An effect of desiccation (a decrease of relative water content from 97% to 10% within 35 h) on Photosystem II was studied in barley leaf segments (Hordeum vulgare L. cv. Akcent) using chlorophyll a fluorescence and thermoluminescence (TL). The O-J-I-P fluorescence induction curve revealed a decrease of F(P) and a slight shift of the J step to a shorter time with no change in its height. The analysis of the fluorescence decline after a saturating light flash revealed an increased portion of slow exponential components with increasing desiccation. The TL bands obtained after excitation by continuous light were situated at about -27 degrees C (Z(v) band - recombination of P680(+)Q(A) (-)), -14 degrees C (A band - S(3)Q(A) (-)), +12 degrees C (B band - S(2/3)Q(B) (-)) and +45 degrees C (C band - TyrD(+)Q(A) (-)). The bands related to the S-states of oxygen evolving complex (A and B) were reduced by desiccation and shifted to higher and lower temperatures, respectively. In accordance with this, the band observed at about +27 degrees C (S(2)Q(B) (-)) after excitation by 1 flash fired at -10 degrees C and band at about +20 degrees C (S(2/3)Q(B) (-)) after 2 flashes decreased with increasing water deficit and shifted to lower temperatures. A new band around 5 degrees C appeared in both regimes of TL excitation for a relative water content of under 42% and was attributed to the Q band (S(2)Q(A) (-)). It is suggested that under desiccation, an inhibition of the formation of S(2)- and S(3)-states in OEC occurred simultaneously with a lowering of electron transport on the acceptor side of PS II. The temperature down-shift of the TL bands obtained after the flash excitation was induced at the initial phases of water stress, indicating a decrease of the activation energy for the S(2/3)Q(B) (-)recombination.

Location of primary and recurrent superficial bladder tumors and benefits of selective biopsies.

Surgical records and bladder diagrams of 856 patients suffering from superficial bladder cancer were summarized into bladder tumor maps. Areas of high tumor density were created giving thus an opportunity to take selective cold cup biopsies. Two hundred and sixteen tissue samples were taken in a group of 62 patients and 12.1% positive results were obtained. The benefit of routinely performed selective biopsies during the first surgery have been discussed.

Immunotherapy of superficial bladder tumors: preliminary results with ImmuCyst--BCG Connaught, Toronto.

A clinical study has been started in 1991 with ImmuCyst (BCG Connaught) as a secondary prophylaxis in urothelial superficial bladder tumors (SBT) patients. Till now 31 patient have been entered into the trial and the results seem to be promising. Only 2 patients were excluded from the study. Side-effects did not extend in average the data quoted in literature and were easily managed. There were 4 recurrences confirmed by cystoscopy. Urinary infection was treated in 7 cases with current chemotherapeutic drugs.

Postoperative cytology in relation to recurrences of superficial bladder tumours.

TNM classification allows only a partial estimation of future tumour behaviour after surgery. More knowledge on malignant potential is needed. Spreading of viable tumour cells during transurethral resection (TUR) and their possible subsequent implantation in the bladder mucosa should be an important factor influencing duration of the tumour-free interval (TFI). A total of 1384 fresh urine samples sequentially taken after surgery from 356 patients were examined in a cytological laboratory. Data analysis confirmed significant differences in TFI between the groups with negative, suspicious and positive cytology. The higher the cytological abnormalities the shorter was TFI, regardless of which histopathological tumour grade has been verified.

[Antiestrogens (tamoxifen) in the alternative therapy of benign prostatic hyperplasia]. / Antiestrogeny (Tamoxifen) v alternativní lécbe benigní hyperplazie prostaty (BPH).

In a non-randomized study the authors administered Tamoxifen to 17 patients with benign prostate hyperplasia who met the criteria for administration of the drug. In the group of patients no significant change of symptoms according to Goldenberg's score was recorded nor changes of prostate size and postmiction residues. In uroflowmetry the significant change of values of maximum flow (p < 0.05) was not associated with a change in the mean flow. The authors assume that monotherapy with Tamoxifen is not effective enough and recommended administration of antioestrogen only in combination with other drugs.

[Alternative therapy of benign prostatic hyperplasia--the Porges Urospiral]. / Alternativní lécba BPH--urospirála Porges.

In patients with benign prostate hyperplasia (BPH) who could not be subjected to surgery because of an associated internal disease the authors ensured by a physical method-insertion of a urospiral-derivation of urine. In 15 patients they recorded favourable results (eradication of urinary infection, a satisfactory stream of urine, continence, complete evacuation of the urinary bladder). All patients improved greatly from the psychic aspect. Personal hygiene was also favourably influenced. Irritation caused by insertion of the urospiral disappeared within several days. Only in one patient the authors removed the urospiral after 6 days because of dysuria and partial incontinence. The authors' initial experience, extending over almost one year, in encouraging and the authors assume that this physical therapeutic method will be more widely applied in the risk patients, in particular patients in advanced age groups.

[Alternative therapy of benign prostatic hypertrophy--Permixon (Capistan)]. / Alternativní lécba BPH--Permixon (Capistan).

In a multicentre study in four urological departments in the Czech Republic the authors evaluated, based on an elaborated protocol, the effect of the preparation Permixon in patients with complaints associated with benign hyperplasia of the prostate (BPH). They followed-up changes of Goldenberg's symptom score and quantitative indicators of urinary flow, postmicturition residues, the prostate volume and other parameters of the urodynamic examination. Statistical evaluation of the results provided evidence of the effectiveness of the preparation which is considered suitable by the authors, in particular in incipient complaints when the patient complains of discomfort during miction and thus of an altered quality of life.

[The effect of extracorporeal shock-wave lithotripsy on renal function]. / Vliv litotrypse extrakorporálními rázovými vlnami na renální funkce.

Using the method of phase scintigraphy, the authors examined 48 patients who were treated by means of extracorporeal shock-wave lithotripsy. The authors proved at the 5% of significance that the development or deterioration of renal functions does not depend on the localization of the concrement and the number of shock-waves needed for disintegration. The authors confirmed the significant effect of the size of concrement on the lesion of renal function--all stones larger than 30 mm lead in 100% to a varying deviation, as compared with the examination made before extracorporeal shock-wave lithotripsy. Obesity has also a significant effect on the development or deterioration of lesions of renal function. From the total number of patients where after lithotripsy a lesion of renal function developed or deteriorated 70.6% were obese! After 24 months in two patients deterioration of the condition, as compared with the initial state, was proved.

[Benign prostatic hyperplasia--alternative (nonsurgical) possibilities of therapy]. / Benigní hyperplazie prostaty (BHP)--alternativní (nechirurgické) moznosti lécby.

The authors summarize contemporary possibilities of alternative treatment of benign hyperplasia of the prostate which could at least partially replace surgery. The authors present also the results of the first clinical investigations using different procedures. The list comprises also experience assembled in Czechoslovak departments.