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1.
Indian J Surg ; : 1-9, 2023 Apr 27.
Article in English | MEDLINE | ID: mdl-37361397

ABSTRACT

Patients with previous abdominal surgery are at an increased risk of peritoneal adhesions, which may complicate transperitoneal surgery. The objective of this article is to report single centre experience with transperitoneal laparoscopic and robotic partial nephrectomy for renal cancer in patients with previous abdominal surgery. We evaluated data from 128 patients who underwent laparoscopic or robotic partial nephrectomy from January 2010 to May 2020. Patients were divided into three groups according to the localization of main previous surgery: in the upper contralateral abdominal quadrant, in the upper ipsilateral abdominal quadrant or in the middle line, in lower abdominal quadrants. Each group was divided into two subgroups (laparoscopic/robotic partial nephrectomy). We separately analysed data of indocyanine green-enhanced robotic partial nephrectomy. Our study did not find significant difference in the rate of intraoperative or postoperative complications between any of the groups. The type of partial nephrectomy (robotic or laparoscopic) affected the surgery time, blood loss, and length of stay in hospital, but did not significantly influence the frequency of complications. Partial nephrectomy in group of patients with prior renal surgery led to a higher rate of intraoperative low-grade complications. We did not observe more favourable results for indocyanine green-enhanced robotic partial nephrectomy. The location of previous abdominal surgery does not influence the rate of intraoperative or postoperative complications. The type of partial nephrectomy (robotic or laparoscopic) does not affect the frequency of complications.

2.
Int J Mol Sci ; 22(1)2021 Jan 05.
Article in English | MEDLINE | ID: mdl-33466491

ABSTRACT

Androgens represent the main hormones responsible for maintaining hormonal balance and function in the prostate and testis. As they are involved in prostate and testicular carcinogenesis, more detailed information of their active concentration at the site of action is required. Since the introduction of the term intracrinology as the local formation of active steroid hormones from inactive precursors of the adrenal gland, mainly dehydroepiandrosterone (DHEA) and DHEA-S, it is evident that blood circulating levels of sex steroid hormones need not reflect their actual concentrations in the tissue. Here, we review and critically evaluate available methods for the analysis of human intraprostatic and intratesticular steroid concentrations. Since analytical approaches have much in common in both tissues, we discuss them together. Preanalytical steps, including various techniques for separation of the analytes, are compared, followed by the end-point measurement. Advantages and disadvantages of chromatography-mass spectrometry (LC-MS, GC-MS), immunoanalytical methods (IA), and hybrid (LC-IA) are discussed. Finally, the clinical information value of the determined steroid hormones is evaluated concerning differentiating between patients with cancer or benign hyperplasia and between patients with different degrees of infertility. Adrenal-derived 11-oxygenated androgens are mentioned as perspective prognostic markers for these purposes.


Subject(s)
Adrenal Glands/metabolism , Androgens/metabolism , Prostate/metabolism , Testis/metabolism , Animals , Gonadal Steroid Hormones/metabolism , Humans , Male , Steroids/metabolism
3.
Contrast Media Mol Imaging ; 2020: 1287530, 2020.
Article in English | MEDLINE | ID: mdl-32410919

ABSTRACT

Partial nephrectomy (PN) is a recommended type of treatment of localised renal tumors. Real-time intraoperative imaging technique, such as fluorescence imaging with indocyanine green (ICG) administration helps to improve intraoperative and postoperative outcomes in patients who underwent PN. Our work presents results of patients who underwent robotic PN with ICG navigation. A total of 37 patients underwent robotic PN with application of ICG between April 2015 and May 2019. A total amount of 5 mg of ICG was applied intravenously, and then robotic PN was performed with fluorescent imaging. ICG was used by the surgeon's decision according to unfavourable anatomical properties of tumor or to high R.E.N.A.L. nephrometry score. An exact border between perfused and nonperfused tissue was detected, and exact tumor's branch of the renal artery was clamped. Robotic PN with ICG-fluorescence imaging navigation was performed in 37 cases with a preoperative average diameter of tumor of 31 mm. The mean surgery time was 133 minutes, and the mean estimated blood loss was 190 mL. Arterial clamping was performed in 35 cases. The mean duration of warm ischemia was 14 minutes. Application of ICG enabled specific tumor-supplying vessel clamping in 25 cases. Two complications of grade II according to the Clavien-Dindo classification occurred intraoperatively, and one complication of grade III was observed. Renal function changes showed favourable results for the cases with superselective clamping. Finally, an administration of ICG eases superselective clamping of tumor-specific branch of renal artery and helps to preserve normal renal function with acceptable oncological results.


Subject(s)
Indocyanine Green/chemistry , Nephrectomy , Optical Imaging , Robotic Surgical Procedures , Adult , Aged , Female , Humans , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/surgery , Male , Middle Aged , Tomography, X-Ray Computed
4.
J Urol ; 199(2): 459-464, 2018 02.
Article in English | MEDLINE | ID: mdl-28867562

ABSTRACT

PURPOSE: A phase 2 study of enzalutamide monotherapy in patients with hormone naïve prostate cancer demonstrated high prostate specific antigen response rates at 25 weeks, 1 year and 2 years with minimal effects on total body bone mineral density and favorable safety. In this followup analysis we evaluated enzalutamide antitumor activity and safety at 3 years. MATERIALS AND METHODS: In a single arm analysis 67 patients with hormone naïve prostate cancer and noncastrate testosterone (230 ng/dl or greater) received enzalutamide 160 mg per day orally until disease progression or unacceptable toxicity. The primary end point was the prostate specific antigen response (80% or greater decline from baseline). RESULTS: No patients discontinued treatment during year 3. Of 42 patients with prostate specific antigen assessments at 3 years 38 (90.5%, 95% CI 77.4-97.3) maintained a prostate specific antigen response. Of 26 patients with metastases at baseline 17 (65.4%) had a complete or partial response as the best overall response during 3 years. In patients who completed the 3-year visit minimal mean changes from baseline were observed in total body bone mineral density or bone mineral density of the femoral neck, trochanter, spine L1-L4 or forearm (range -2.7% to -0.1%). At 3 years total body fat had increased a mean of 16.5%, total lean body mass had decreased a mean of -6.5% and global health status had minimally decreased from baseline. Common adverse events were gynecomastia, fatigue, hot flush and nipple pain. CONCLUSIONS: Enzalutamide antitumor activity was maintained in patients with hormone naïve prostate cancer at 3 years. Overall bone mineral density, global health status and safety results were similar to those at 2 years.


Subject(s)
Antineoplastic Agents/therapeutic use , Phenylthiohydantoin/analogs & derivatives , Prostatic Neoplasms/drug therapy , Administration, Oral , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Benzamides , Follow-Up Studies , Humans , Male , Middle Aged , Nitriles , Phenylthiohydantoin/adverse effects , Phenylthiohydantoin/therapeutic use , Treatment Outcome
5.
Talanta ; 174: 21-28, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-28738570

ABSTRACT

In this study, a novel liquid chromatography - tandem mass spectrometry method for the simultaneous determination of bisphenols (BPA, BPS, BPF, BPAF), parabens (methyl-, ethyl-, propyl-, butyl-, benzyl-paraben) and estrogens (estrone, estradiol, estriol) in human plasma is presented. Since all analytes possess the phenolic group, dansyl chloride derivatization was applied in order to gain high sensitivity. The method was validated according to FDA guidelines, and all validation requirements were satisfactory. The lower limits of quantifications were 41.6, 54.9, 43.5 and 150.8pg/mL for BPA, BPS, BPF and BPAF; 172, 149, 171, 134 and 202pg/mL for methyl-, ethyl-, propyl-, butyl- and benzyl-paraben; 10.5, 6.7 and 9.4pg/mL for estrone, estradiol and estriol, respectively. This is the first method allowing the determination of plasma bisphenols, parabens and estrogens in one run, and also the first determination of BPF levels in human plasma. The method was used to examine the plasma levels of healthy normospermic men, where three times higher plasma levels of BPF than BPA were found.


Subject(s)
Blood Chemical Analysis/methods , Estrogens/blood , Parabens/analysis , Phenols/blood , Chromatography, Liquid , Humans , Limit of Detection , Tandem Mass Spectrometry
6.
Environ Int ; 89-90: 166-73, 2016.
Article in English | MEDLINE | ID: mdl-26863184

ABSTRACT

BACKGROUND: In the testis, steroid hormones play an important role in spermatogenesis, the production of semen, and the maintenance of secondary sex characteristics and libido. They may also play a role as a target for substances called endocrine disruptors (EDs). As yet, however, no complex study has been conducted evaluating the relationships between EDs and the steroid spectrum in the plasma and seminal plasma. OBJECTIVES: To shed more light into mechanisms of EDs and the effects of bisphenol A (BPA) and polychlorinated biphenyls (PCBs) on human spermatogenesis and steroidogenesis. METHODS: We determined BPA and 11 steroids in the plasma and seminal plasma of 191 men with different degrees of fertility, using a newly developed liquid-chromatography mass spectrometry method. Concurrently, plasma levels of 6 congeners of PCBs, gonadotropins, selenium, zinc and homocysteine were measured. Partial correlations adjusted for age, BMI and abstinence time were performed to evaluate relationships between these analytes. RESULTS: Seminal BPA, but not plasma BPA, was negatively associated with sperm concentration (r=-0.198; p=0.009), sperm count (r=-0.178; p=0.018) and morphology (r=-0.160; p=0.044). Divergent and sometimes opposing associations of steroids and BPA were found in both body fluids. The sum of PCB congeners was negatively associated with testosterone, free testosterone, the free androgen index and dihydrotestosterone in plasma. CONCLUSION: BPA may negatively contribute to the final state of sperm quality. Moreover, our data indicate that BPA influences human gonadal and adrenal steroidogenesis at various steps. Environmental levels of PCBs negatively correlated with androgen levels, but surprisingly without negative effects on sperm quality.


Subject(s)
Benzhydryl Compounds/analysis , Endocrine Disruptors/analysis , Gonadal Steroid Hormones/blood , Infertility, Male/epidemiology , Phenols/analysis , Polychlorinated Biphenyls/analysis , Semen/chemistry , Spermatogenesis/drug effects , Adult , Benzhydryl Compounds/blood , Benzhydryl Compounds/toxicity , Chromatography, Liquid/methods , Endocrine Disruptors/blood , Endocrine Disruptors/toxicity , Humans , Infertility, Male/blood , Infertility, Male/chemically induced , Male , Phenols/blood , Phenols/toxicity , Polychlorinated Biphenyls/blood , Polychlorinated Biphenyls/toxicity , Semen/drug effects , Sperm Count , Spermatozoa/chemistry , Spermatozoa/drug effects , Spermatozoa/pathology , Testosterone/blood
7.
J Steroid Biochem Mol Biol ; 155(Pt B): 207-16, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25066675

ABSTRACT

Numerous chemicals in the environment have the ability to interact with the endocrine system. These compounds are called endocrine disruptors (EDs). Exposure to EDs represents one of the hypotheses for decreasing fertility, the increased risk of numerous cancers and obesity, metabolic syndrome and type 2 diabetes. There are various mechanisms of ED action, one of which is their interference in the action of 11ß-hydroxysteroid dehydrogenase (11ßHSD) that maintains a balance between active and inactive glucocorticoids on the intracellular level. This enzyme has two isoforms and is expressed in various tissues. Inhibition of 11ßHSD in various tissues can have different consequences. In the case of EDs, the results of exposure are mainly adverse; on the other hand pharmaceutically developed inhibitors of 11ßHSD type 1 are evaluated as an option for treating metabolic syndrome, as well as related diseases and depressive disorders. This review focuses on the effects of 11ßHSD inhibitors in the testis, colon, adipose tissue, kidney, brain and placenta.


Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists & inhibitors , 11-beta-Hydroxysteroid Dehydrogenase Type 2/antagonists & inhibitors , Endocrine Disruptors/pharmacology , Enzyme Inhibitors/pharmacology , 11-beta-Hydroxysteroid Dehydrogenase Type 1/metabolism , 11-beta-Hydroxysteroid Dehydrogenase Type 2/metabolism , Adipose Tissue/drug effects , Adipose Tissue/enzymology , Brain/drug effects , Brain/enzymology , Colon/drug effects , Colon/enzymology , Diabetes Mellitus/chemically induced , Diabetes Mellitus/enzymology , Diabetes Mellitus/pathology , Female , Glucocorticoids/metabolism , Humans , Male , Metabolic Syndrome/chemically induced , Metabolic Syndrome/enzymology , Metabolic Syndrome/pathology , Neoplasms/chemically induced , Neoplasms/enzymology , Neoplasms/pathology , Obesity/chemically induced , Obesity/enzymology , Obesity/pathology , Organ Specificity , Placenta/drug effects , Placenta/enzymology , Pregnancy , Testis/drug effects , Testis/enzymology
8.
Talanta ; 140: 62-67, 2015 Aug 01.
Article in English | MEDLINE | ID: mdl-26048824

ABSTRACT

Bisphenol A (BPA) is a widely known endocrine disruptor with estrogenic, antiestrogenic or antiandrogenic properties. BPA could interfere with estrogen metabolism as well with receptor-mediated estrogen actions. Both environmental BPA and estrogens may be traced in body fluids, of which, besides the blood plasma, the seminal fluid is of particular interest regarding their possible interactions in the testis. The method for simultaneously determining BPA and estrogens is then needed, taking into account that their concentrations in these body fluid may differ. Here the method was developed and validated for measurements of BPA, estrone (E1), estradiol (E2) and estriol (E3) in blood plasma and seminal plasma using liquid chromatography-tandem mass spectrometry. Due to the phenolic moiety of all compounds, dansyl chloride derivatization could be used. The analytical criteria of the method with respect to expected concentration of the analytes were satisfactory. The lower limits of quantifications (LLOQ) amounted to 43.5, 4.0, 12.7, 6.7 pg/mL for plasma BPA, E1, E2 and E3, and 28.9, 4.9, 4.5, 3.4 pg/mL for seminal BPA, E1, E2 and E3, respectively. The concentrations of individual steroids differed between body fluids. To the best of our knowledge, this is the first method that enabled the measurement of estrogens and BPA together in one run. The concentrations of E1, E2 and for the first time also of E3 in seminal plasma in normospermic men are reported.


Subject(s)
Benzhydryl Compounds/blood , Endocrine Disruptors/blood , Estrogens/blood , Phenols/blood , Semen/chemistry , Tandem Mass Spectrometry/methods , Benzhydryl Compounds/analysis , Chromatography, Liquid/methods , Endocrine Disruptors/analysis , Estrogens/analysis , Estrone/analysis , Estrone/blood , Humans , Limit of Detection , Male , Phenols/analysis
9.
Syst Biol Reprod Med ; 61(4): 245-50, 2015.
Article in English | MEDLINE | ID: mdl-26043179

ABSTRACT

Male infertility is a serious problem in an increasing number of couples. We report an infertile man with non-obstructive azoospermia and karyotype 45,XY,rob(14;22). The immunofluorescence analysis of his testicular tissue using antibodies to SYCP1, SYCP3, HORMAD2, MLH1, and centromeres showed delayed synapsis of the chromosomes involved in the translocation, a varying extent of trivalent asynapsis and its association with sex chromosomes. The mean frequency of meiotic recombination per cell was within the range of normal values. Fluorescence in situ hybridization (FISH) with probes for chromosomes 14 and 22 revealed 5.83% of chromosomally abnormal testicular spermatozoa. FISH with probes for chromosomes X, Y, and 21 showed frequencies of disomic and diploid testicular spermatozoa increased when compared to ejaculated sperm of healthy donors, but comparable with published results for azoospermic patients. PGD by FISH for the translocation and aneuploidy of chromosomes X, Y, 13, 18, and 21 showed a normal chromosomal complement in one out of three analyzed embryos. A healthy carrier girl was born after the embryo transfer. This study shows the benefits of preimplantation genetic diagnosis in a case of a rare Robertsonian translocation carrier with azoospermia and a relatively low frequency of chromosomally unbalanced testicular spermatozoa.


Subject(s)
Aneuploidy , Azoospermia/genetics , Chromosomes, Human, Pair 14 , Chromosomes, Human, Pair 22 , Genetic Carrier Screening , Meiosis/genetics , Spermatozoa/metabolism , Translocation, Genetic , Humans , Karyotyping , Male
10.
Eur Urol ; 68(5): 787-94, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25687533

ABSTRACT

BACKGROUND: Enzalutamide is an androgen receptor inhibitor with a demonstrated overall survival benefit in metastatic castration-resistant prostate cancer. A phase 2 study of enzalutamide monotherapy in patients with hormone-naïve prostate cancer (HNPC) showed a high response rate for the prespecified primary endpoint (ie, prostate-specific antigen [PSA] response at week 25), regardless of metastases at baseline, and favorable tolerability. OBJECTIVE: To determine the long-term efficacy and safety of enzalutamide monotherapy at 1 and 2 yr. DESIGN, SETTING, AND PARTICIPANTS: Open-label, single-arm study in patients with HNPC and noncastrate testosterone (≥230 ng/dl). INTERVENTION: Oral enzalutamide 160mg/d until disease progression or unacceptable toxicity. OUTCOME MEASUREMENTS AND ANALYSIS: PSA response (≥80% decline from baseline) assessed at 1 yr (49 wk) and 2 yr (97 wk). RESULTS AND LIMITATIONS: The median (range) age was 73 (48-86) yr and 26 patients (39%) presented with metastases at study entry. Of 67 patients enrolled, 45 (67%) remained on enzalutamide at week 97. For patients remaining on therapy, the PSA response rate at week 97 was 100% (95% confidence interval 92-100%). Of 26 patients with metastases at baseline, 13 (50%) had a complete and four (15.4%) had a partial response as best overall tumor response up to 97 wk on treatment. There was overall maintenance of total-body bone mineral density (BMD) and moderate changes in lean and fat body mass at 49 and 97 wk. The most common adverse events were gynecomastia, nipple pain, fatigue, and hot flushes. The study limitations include lack of a control group and of endocrine, glycemic, and lipid data at 97 wk. CONCLUSIONS: Long-term enzalutamide monotherapy in men with noncastrate HNPC is associated with large sustained reductions in PSA, signals indicating a favorable tumor response, and favorable safety/tolerability profile, with relatively small negative effects on total-body BMD. PATIENT SUMMARY: In this long-term follow-up of the efficacy and safety of enzalutamide monotherapy in patients with hormone-naïve prostate cancer, enzalutamide maintained long-term reductions in prostate-specific antigen, with a minimal impact on total-body bone mineral density. TRIAL REGISTRATION: NCT01302041.


Subject(s)
Androgen Receptor Antagonists/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Neoplasm Recurrence, Local/blood , Phenylthiohydantoin/analogs & derivatives , Prostatectomy , Prostatic Neoplasms/drug therapy , Aged , Aged, 80 and over , Benzamides , Chemotherapy, Adjuvant , Follow-Up Studies , Humans , Kallikreins/blood , Longitudinal Studies , Male , Middle Aged , Nitriles , Phenylthiohydantoin/therapeutic use , Prostate-Specific Antigen/blood , Prostatic Neoplasms/pathology , Treatment Outcome
11.
Lancet Oncol ; 15(6): 592-600, 2014 May.
Article in English | MEDLINE | ID: mdl-24739897

ABSTRACT

BACKGROUND: The androgen receptor inhibitor enzalutamide is approved for the treatment of metastatic castration-resistant prostate cancer that has progressed on docetaxel. Our aim was to assess the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer. METHODS: This trial is an ongoing open-label, single-arm, phase 2 study, done across 12 European sites. Men aged over 18 years, with hormone-naive prostate cancer for whom hormone therapy was indicated, and who had non-castration levels of testosterone and prostate-specific antigen (PSA) of 2 ng/mL or greater at screening, and an Eastern Cooperative Oncology Group score of 0, received oral enzalutamide 160 mg/day. The primary outcome was the proportion of patients with an 80% or greater decline in PSA at week 25. All analyses included all patients who had received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT01302041. FINDINGS: 67 men were enrolled into the study. 62 patients (92.5%, 95% CI 86.2-98.8) had a decline in PSA of 80% or greater at week 25. The most commonly reported treatment-emergent adverse events up to week 25 were gynaecomastia (n=24), fatigue (n=23), nipple pain (n=13), and hot flush (n=12), all of which were of mild to moderate severity. Nine patients had a treatment-emergent adverse event of grade 3 or higher, most of which were reported in one patient each, except for pneumonia (grade 3, two patients) and hypertension (grade 3, four patients). Five patients reported serious adverse events, none of which were deemed to be treatment related. INTERPRETATION: Our findings suggest that enzalutamide monotherapy in men with hormone-naive prostate cancer of varying severity provides a level of disease suppression, and was generally well tolerated. These findings provide a rationale for further investigation of clinical response and outcomes with enzalutamide in non-castrate men with prostate cancer.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents/therapeutic use , Phenylthiohydantoin/analogs & derivatives , Prostatic Neoplasms/drug therapy , Adenocarcinoma/blood , Aged , Aged, 80 and over , Androgen Antagonists/therapeutic use , Benzamides , Humans , Male , Middle Aged , Nitriles , Phenylthiohydantoin/therapeutic use , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Treatment Outcome
12.
Urol Oncol ; 31(7): 951-65, 2013 Oct.
Article in English | MEDLINE | ID: mdl-22459691

ABSTRACT

BACKGROUND: The potential role of genitourinary infection in the etiology of prostate cancer (CaP) has been extensively investigated for 30 years. Two basic approaches have been used: tissue-based methods (polymerase chain reaction, immunohistochemistry, and in situ hybridization) and serologic assays (enzyme-linked immunosorbent assay, immunofluorescence, etc.). The objective of this review was to answer the question of whether infection of the male genitourinary tract may have a role in the etiology of CaP. MATERIALS AND METHODS: We have carried out a systematic review of the evidence that was published in the MEDLINE/PubMed database until December 2011. The search terms included "prostate cancer," "infection," and the explicit names of the various infectious agents. Additional studies were identified using a reference search. A total of 74 papers were included in the review, which cover the following infectious agents: human papillomavirus, cytomegalovirus, herpes simplex virus, Epstein-Barr virus, human herpesvirus, BK virus, JC virus, chlamydia, mycoplasma, ureaplasma, trichomonas, neisseria, treponema, Propionibacterium acnes, xenotropic murine leukemia virus-related virus and Candida albicans. RESULTS: Despite the variable study designs and methodological approaches that were used, most of the pathogens that were studied were unlikely to be directly involved in prostate carcinogenesis. CONCLUSIONS: The role of infection in the etiology of CaP has yet to be determined despite 30 years of research efforts. A discovery of an infectious agent that is associated with CaP would be of great medical importance; however, such a link would have to be firmly established before impacting on patient care.


Subject(s)
Bacterial Infections/diagnosis , Mycoses/diagnosis , Prostatic Neoplasms/diagnosis , Virus Diseases/diagnosis , Bacterial Infections/complications , Humans , Male , Mycoses/complications , Prostatic Neoplasms/etiology , Risk Assessment , Risk Factors , Virus Diseases/complications
13.
Horm Mol Biol Clin Investig ; 13(1): 1-5, 2013 Jun.
Article in English | MEDLINE | ID: mdl-25436708

ABSTRACT

The data on hormonal steroids in the human seminal plasma and their role in spermatogenesis are summarized. The seminal steroid levels need not correlate with the blood plasma levels. The recent reports showed that androgen, especially dihydrotestosterone, and the estrogen levels in the seminal fluid may be used as the markers of spermatogenesis impairment. The estradiol concentration in the seminal plasma was higher than in the blood plasma, and its levels were significantly increased in men with impaired spermatogenesis. A good indicator for predicting the normal spermatogenesis, therefore, seems to be the testosterone/estradiol ratio. The seminal plasma also contains significant amounts of cortisol, which influences the androgen biosynthesis through its receptors in the Leydig cells. The local balance between cortisol and inactive cortisone is regulated by 11ß-hydroxysteroid dehydrogenase, the activity of which may be affected by the environmental chemicals acting as the endocrine disruptors (EDCs). These compounds are believed to participate in worsening the semen quality - the sperm count, motility, and morphology, as witnessed in the recent last decades. As to the steroids' role in the testis, the EDCs may act as antiandrogens by inhibiting the enzymes of testosterone biosynthesis, as the agonists or antagonists through their interaction with the steroid hormone receptors, or at the hypothalamic-pituitary-gonadal axis. Surprisingly, though the EDCs affect the steroid action in the testis, there is no report of a direct association between the concentrations of steroids and the EDCs in the seminal fluid. Therefore, measuring the steroids in the semen, along with the various EDCs, could help us better understand the role of the EDCs in the male reproduction.


Subject(s)
Endocrine Disruptors/metabolism , Semen/cytology , Semen/metabolism , Spermatogenesis , Steroids/metabolism , Animals , Humans , Male , Reproduction , Semen/chemistry , Steroids/analysis
14.
Klin Mikrobiol Infekc Lek ; 18(5): 150-5, 2012 Oct.
Article in Czech | MEDLINE | ID: mdl-23208869

ABSTRACT

This review article provides information on the impact of HIV-1 on male reproductive functions. HIV-positive patients of reproductive age with now a long-term prognosis may wish to have children. If only one partner is infected, natural conception brings the risk of virus transmission. The article reviews the reproduction possibilities for HIV-positive couples and explains the ways to reduce the risk of transmitting the virus to the healthy partner or a child. Assisted reproduction techniques, especially intrauterine insemination, in vitro fertilization and intracytoplasmic sperm injection in combination with sperm washing can successfully reduce the risk of HIV transmission. Current trends and dilemmas of infertility treatment in HIV-positive couples are discussed.


Subject(s)
HIV Infections/complications , HIV-1 , Infectious Disease Transmission, Vertical , Infertility, Male/etiology , Reproductive Techniques, Assisted , Female , HIV Infections/transmission , Humans , Infertility, Male/therapy , Male
15.
Cas Lek Cesk ; 151(8): 392-6, 2012.
Article in Czech | MEDLINE | ID: mdl-23101893

ABSTRACT

BACKGROUND: The aim of the study was to evaluate prostate transrectal ultrasonography findings in men with congenital hypogonadism treated by long term testosterone replacement therapy. METHODS: We have gradually included 31 men with congenital hypogonadism in period of 2001-2011. The average follow-up was 7.3 years (2 months - 10.8 years). We have used Sustanon® 250 i.m. every 3 weeks or Nebido® i.m. every 3 months for continual testosterone replacement therapy. We performed to all patients the transrectal ultrasonography of prostate and seminal vesicles by biplanar rectal probe every 6 months. RESULTS: During the transrectal ultrasonography we observed in 22 (71.0 %) patients changes in prostatic tissue. In case of 12 patients were diagnosed asymptomatic prostatic cysts, in 9 patients prostatolithiasis and in 5 patients changes in echogenity of prostatic tissue. In 2 patients was found simultaneous occurrence of prostatic cyst and prostolithiasis, in further 2 patients simultaneous occurrence of hyperechogenic prostatic lesion and prostatolithiasis. The above described findings were diagnosed in 5 patients in the treatment lasting from 3 to 5 years, for the other 17 men with hormone replacement therapy longer than 5 years. CONCLUSIONS: The study presents long term results of complex treatment in patients with disorders of sexual development, onset and progress of puberty. The long term treatment of these patients in interdisciplinary cooperation of endocrinologist and andrologist may significantly contribute to clarify an impact of testosterone replacement therapy on prostate development.


Subject(s)
Hormone Replacement Therapy , Hypogonadism/drug therapy , Prostate/diagnostic imaging , Testosterone/therapeutic use , Adolescent , Adult , Hormone Replacement Therapy/adverse effects , Humans , Hypogonadism/congenital , Male , Prostatic Diseases/chemically induced , Prostatic Diseases/diagnostic imaging , Testosterone/adverse effects , Ultrasonography , Young Adult
16.
J Med Virol ; 84(10): 1636-45, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22930513

ABSTRACT

HPV has carcinogenic effects at several anatomical sites in women and men. Whether the presence of HPV in the genitourinary tract of men is associated with a higher prostate cancer risk has been a matter of research for a long-time and the results are still not fully conclusive. Similarly, the question of the reservoir of HPV infection in men is not clearly resolved. HPV DNA presence and types were evaluated by means of polymerase chain reaction in the tissue of 146 patients with benign prostate hyperplasia and prostate cancer. HPV-specific antibodies were analyzed by enzyme-linked immunosorbent assay in the sera of all patients and 172 controls. In addition, 256 biopsies taken from non-tumorous tissues were analyzed. No statistically significant differences were observed in HPV DNA prevalence between patients with benign prostate hyperplasia (2%) and patients with prostatic cancer (2%; P = 1.000). The seropositivity rates did not differ significantly between groups of subjects except for antibodies against HPV 6 VLPs which were found more often in prostate cancer patients (adjusted P = 0.018). Similarly, no difference in the seroprevalence rates for HPV 16 E6 and/or E7 oncoproteins between groups of patients and healthy controls was detected. The overall HPV prevalence in 256 healthy tissue samples was 4%. The results indicate that HPV infection is not associated with prostate oncogenesis in men. However, they imply that multiple tissues of the male genitourinary tract may be important reservoirs for the transmission of some HPV types.


Subject(s)
Papillomaviridae/isolation & purification , Papillomaviridae/pathogenicity , Papillomavirus Infections/complications , Papillomavirus Infections/virology , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/virology , Aged , Aged, 80 and over , Antibodies, Viral/blood , Biopsy , DNA, Viral/isolation & purification , Enzyme-Linked Immunosorbent Assay , Genotype , Humans , Male , Middle Aged , Papillomaviridae/classification , Papillomaviridae/genetics , Polymerase Chain Reaction , Prevalence
17.
Nucleic Acids Res ; 39(20): 8728-39, 2011 Nov 01.
Article in English | MEDLINE | ID: mdl-21771862

ABSTRACT

Syncytin-1 and -2, human fusogenic glycoproteins encoded by the env genes of the endogenous retroviral loci ERVWE1 and ERVFRDE1, respectively, contribute to the differentiation of multinucleated syncytiotrophoblast in chorionic villi. In non-trophoblastic cells, however, the expression of syncytins has to be suppressed to avoid potential pathogenic effects. We studied the epigenetic suppression of ERVWE1 and ERVFRDE1 5'-long terminal repeats by DNA methylation and chromatin modifications. Immunoprecipitation of the provirus-associated chromatin revealed the H3K9 trimethylation at transcriptionally inactivated syncytins in HeLa cells. qRT-PCR analysis of non-spliced ERVWE1 and ERVFRDE1 mRNAs and respective env mRNAs detected efficient splicing of endogenously expressed RNAs in trophoblastic but not in non-placental cells. Pointing to the pathogenic potential of aberrantly expressed syncytin-1, we have found deregulation of transcription and splicing of the ERVWE1 in biopsies of testicular seminomas. Finally, ectopic expression experiments suggest the importance of proper chromatin context for the ERVWE1 splicing. Our results thus demonstrate that cell-specific retroviral splicing represents an additional epigenetic level controling the expression of endogenous retroviruses.


Subject(s)
Endogenous Retroviruses , Epigenesis, Genetic , Gene Products, env/genetics , Pregnancy Proteins/genetics , RNA Splicing , Transcription, Genetic , Cell Line , Gene Products, env/metabolism , Gene Silencing , Glycoproteins/genetics , Glycoproteins/metabolism , HeLa Cells , Histones/metabolism , Humans , Male , Neoplasms, Germ Cell and Embryonal/genetics , Neoplasms, Germ Cell and Embryonal/metabolism , Pregnancy Proteins/metabolism , Proviruses/genetics , Proviruses/metabolism , RNA, Messenger/metabolism , Testis/metabolism
18.
BMC Cancer ; 11: 53, 2011 Feb 03.
Article in English | MEDLINE | ID: mdl-21291519

ABSTRACT

BACKGROUND: Infection plays a role in the pathogenesis of many human malignancies. Whether prostate cancer (PCa) - an important health issue in the aging male population in the Western world - belongs to these conditions has been a matter of research since the 1970 s. Persistent serum antibodies are a proof of present or past infection. The aim of this study was to compare serum antibodies against genitourinary infectious agents between PCa patients and controls with benign prostate hyperplasia (BPH). We hypothesized that elevated serum antibody levels or higher seroprevalence in PCa patients would suggest an association of genitourinary infection in patient history and elevated PCa risk. METHODS: A total of 434 males who had undergone open prostate surgery in a single institution were included in the study: 329 PCa patients and 105 controls with BPH. The subjects' serum samples were analysed by means of enzyme-linked immunosorbent assay, complement fixation test and indirect immunofluorescence for the presence of antibodies against common genitourinary infectious agents: human papillomavirus (HPV) 6, 11, 16, 18, 31 and 33, herpes simplex virus (HSV) 1 and 2, human cytomegalovirus (CMV), Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Neisseria gonorrhoeae and Treponema pallidum. Antibody seroprevalence and mean serum antibody levels were compared between cases and controls. Tumour grade and stage were correlated with serological findings. RESULTS: PCa patients were more likely to harbour antibodies against Ureaplasma urealyticum (odds ratio (OR) 2.06; 95% confidence interval (CI) 1.08-4.28). Men with BPH were more often seropositive for HPV 18 and Chlamydia trachomatis (OR 0.23; 95% CI 0.09-0.61 and OR 0.45; 95% CI 0.21-0.99, respectively) and had higher mean serum CMV antibody levels than PCa patients (p = 0.0004). Among PCa patients, antibodies against HPV 6 were associated with a higher Gleason score (p = 0.0305). CONCLUSIONS: Antibody seropositivity against the analyzed pathogens with the exception of Ureaplasma does not seem to be a risk factor for PCa pathogenesis. The presence or higher levels of serum antibodies against the genitourinary pathogens studied were not consistently associated with PCa. Serostatus was not a predictor of disease stage in the studied population.


Subject(s)
Antibodies, Bacterial/blood , Antibodies, Viral/blood , Male Urogenital Diseases/immunology , Prostatic Hyperplasia/immunology , Prostatic Neoplasms/immunology , Adult , Aged , Aged, 80 and over , Alphapapillomavirus/immunology , Case-Control Studies , Chlamydia trachomatis/immunology , Complement Fixation Tests , Cytomegalovirus/immunology , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique, Indirect , Humans , Male , Male Urogenital Diseases/microbiology , Male Urogenital Diseases/virology , Middle Aged , Mycoplasma hominis/immunology , Neisseria gonorrhoeae/immunology , Prostate/pathology , Prostate/surgery , Prostatectomy , Prostatic Hyperplasia/blood , Prostatic Neoplasms/blood , Simplexvirus/immunology , Species Specificity , Treponema pallidum/immunology , Ureaplasma urealyticum/immunology
19.
Cas Lek Cesk ; 149(1): 16-20, 2010.
Article in Czech | MEDLINE | ID: mdl-20662455

ABSTRACT

Approximately 15% of men with newly diagnosed cancer are younger than 55 years, and about 26% of them are younger than 20 years. However the most common cause of fertility disorders is oncological treatment itself, the oncological diseases, changes in anatomy, and primary or secondary hormonal insufficiency are also significant factors. The chemotherapy, radiation, or their combination reduce sperm count, impair sperm motility and cause disorders in morphology and DNA integrity. Prognosis of sperm production recovery depends on the type of cancer, stage of the disease, patient age, drug treatment, treatment route and dosage, and pre-treatment male fertility.


Subject(s)
Infertility, Male/etiology , Neoplasms/therapy , Antineoplastic Agents/adverse effects , Humans , Male , Radiotherapy/adverse effects
20.
Cas Lek Cesk ; 149(3): 115-9, 2010.
Article in Czech | MEDLINE | ID: mdl-20429346

ABSTRACT

As life expectancy of patients infected by Human Immunodeficiency Virus (HIV) has prolonged, they are treated by physicians of different specialities. This article focuses on urologic complications of HIV infection. Urinary tract infections in HIV positive patients are more frequent than in otherwise healthy individuals and less common microorganisms can be involved. Sexually transmitted diseases are a commonplace. Certain malignancies of the genitourinary tract are more often diagnosed in HIV positive than in HIV negative population. Impairment of kidney function is usually caused by HIV-associated nephropathy. Acute renal failure can also occur. Indinavir causes urinary stones formation. Male circumcision is an effective method of HIV transmission prevention.


Subject(s)
HIV Infections/complications , Urologic Diseases/complications , AIDS-Associated Nephropathy/complications , HIV Infections/prevention & control , Humans , Urinary Tract Infections/complications , Urogenital Neoplasms/complications
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