Synergistic Effect of Ceftazidime-Avibactam with Aztreonam on Carbapenemase-Positive Klebsiella pneumoniae MBL+, NDM.

Background: The difficulties in attaining effective antibiotic therapy arising from the multidrug resistance of Gram-negative bacilli compel the exploration of new possibilities for synergistic interactions among existing antibiotics. Research Design and Methods: An analysis was conducted to assess the efficacy of two antibiotic therapy regimens in the treatment of infections caused by Klebsiella pneumoniae strains producing carbapenemases (MBL). Two patient groups were considered: Group A - individuals in whom the treatment of infection involved the application of ceftazidime-avibactam in combination with aztreonam. Group B comprised patients subjected to an alternative antibiotic therapy regimen. Results: In the group subjected to the treatment regimen involving ceftazidime-avibactam and aztreonam, as compared to alternative antibiotic combinations, a statistically lower mortality rate during the course of treatment and a faster clinical response to the administered therapy were evident. Conclusion: The results obtained may be applicable to routine in vitro assays performed and serve as valuable guidance for the potential utilization of the positive effect of antibiotic therapy through the synergy between ceftazidime-avibactam and aztreonam. The selection of antibiotics employed in the therapy of invasive infections caused by K. pneumoniae influences the ultimate treatment outcome.

The role of the intrinsic pathway of apoptosis in human ejaculated sperm damage under a state of scrotal heat stress.

PURPOSE: The study aimed to determine the associations among standard sperm characteristics and oxidative/apoptotic markers in ejaculated sperm of men exposed to prolonged scrotal hyperthermia of either environmental or clinical origin. METHODS: The original study design included four research groups: professional drivers (n = 54), infertile men with varicocele (n = 78), infertile men not exposed to prolonged genital heat stress (n = 37), and fertile individuals serving as the control group (n = 29). Standard semen analysis was performed according to the 5th WHO laboratory manual. The following oxidative and apoptotic parameters of sperm were investigated: mitochondrial superoxide anion generation (MitoSOX Red dye), phosphatidylserine externalization (Annexin V binding assay), mitochondrial membrane potential (JC-1 dye), DNA fragmentation (TUNEL/PI assay), and membrane fluidity (merocyanine 540 dye). RESULTS: All the studied groups presented a strong deterioration in routine sperm parameters and a strongly apoptotic phenotype in sperm, characterized by both decreased mitochondrial membrane potential and enhanced DNA fragmentation, regardless of the thermal insult. Significant induction of mitochondrial superoxide anion generation was noted only in the groups exposed to genital heat stress. A positive correlation between the production of superoxide anion in the mitochondrial chain and the level of DNA fragmentation in drivers was also noted. CONCLUSION: Long-term exposure to scrotal hyperthermia in real-life situations is sufficient to reduce sperm quality in humans. The thermal stress directly induces the oxidative stress cascade in ejaculated sperm, affecting the plasma membrane fluidity, mitochondrial homeostasis, and sperm DNA integrity.

Low human sperm motility coexists with sperm nuclear DNA damage and oxidative stress in semen.

BACKGROUND: Low sperm motility, one of the common causes of male infertility, is associated with abnormal sperm quality. Currently, important sperm/semen biomarkers are sperm chromatin status and oxidation-reduction potential (ORP) in semen. Because the association between sperm motility and these biomarkers is still not fully clarified, our study was designed to verify the distribution and risk of sperm DNA fragmentation (SDF) and oxidative stress in semen in asthenozoospermic men. MATERIALS AND METHODS: This study was carried out on discharged sperm cells of asthenozoospermic men (isolated asthenozoospermia or coexisted with reduced sperm number and/or morphology), nonasthenozoospermic men (reduced total sperm count and/or sperm morphology) (experimental groups) and normozoospermic men (proven and presumed fertility) (control group). Basic semen analysis was evaluated according to the 6th edition of the World Health Organization manual guidelines. SDF was assessed using the sperm chromatin dispersion test, while static(s) ORP in semen was measured by means of a MiOXSYS analyser. RESULTS: The men from the asthenozoospermic group had lower basic semen parameters than those from the control and nonasthenozoospermic groups. In men with poor sperm motility SDF and sORP, prevalence and risk for > 20% SDF (high level of DNA damage) and for > 1.37 sORP (oxidative stress) were significantly higher than those of control and nonasthenozoospermic subjects. The risk for sperm DNA damage and oxidative stress in asthenozoospermic men was over 10-fold higher and almost 6-fold higher than those in control subjects and almost or over 3-fold higher than those in nonasthenozoospermic men. CONCLUSIONS AND DISCUSSION: Poor human sperm motility coexisted with low basic sperm quality. Sperm DNA damage and oxidative stress in semen were much more frequent in asthenozoospermia. These abnormalities can decrease the sperm fertilizing capability under both natural and medically assisted reproduction conditions. Thus, in asthenozoospermia, the evaluation of sperm chromatin status and oxidation-reduction potential in semen is justified and inevitable, and the appropriate antioxidant therapy can be suggested.

The long-term effects of multidrug immunosuppressive protocols based on calcineurin inhibitors and conversion to rapamycin on the morphology, apoptosis, and proliferation of rat salivary glands.

BACKGROUND: The effect of multidrug immunosuppressive protocols on the salivary glands is still unknown. This study aimed to determine the influence of immunosuppressive regimens based on calcineurin inhibitors (CNIs) and conversion to rapamycin on the morphology, apoptosis, and proliferation of rat salivary glands. METHODS: Male rats received cyclosporin A (CsA), tacrolimus (FK-506), mycophenolate mofetil (MMF), rapamycin (Rapa), and prednisone (Pre) according to three-drug protocols: CMP (CsA, MMF, and Pre), CMP/R (CsA, MMF, and Pre with conversion to Rapa), TMP (FK-506, MMF, and Pre), and TMP/R (FK-506, MMF, and Pre with conversion to Rapa). Morphological and immunohistochemical and quantitative analyses of the salivary glands were performed. RESULTS: Structural changes in salivary glands were observed in all experimental groups, especially in the submandibular gland. In the salivary glands, the percentages of collagen fibers and TUNEL-, Ki67- and PCNA-positive cells were higher in the experimental groups vs. the control but were lower in the CMP/R and TMP/R groups vs. the CMP and TMP groups, with the exception of collagen fibers in the parotid gland in the TMP/R group vs. the TMP group. CONCLUSIONS: Long-term administration of CNIs in triple regimens and after conversion to rapamycin monotherapy, causes morphological changes in the salivary glands of rats. Immunosuppressive treatment based on CNIs is associated with an increase in collagen accumulation. The effects of the conversion of treatment with CNIs to rapamycin in immunosuppressive protocols in rat salivary glands lead to decreased fibrosis, apoptosis, and proliferation. These changes may possibly prevent abnormalities resulting from the application of CNIs.

Male Infertility Coexists with Decreased Sperm Genomic Integrity and Oxidative Stress in Semen Irrespective of Leukocytospermia.

Our research was designed to verify the relationship between male infertility, basic semen characteristics (with respect to detailed sperm morphology), sperm DNA fragmentation (SDF), oxidation-reduction potential in semen (ORP), and leukocytospermia. The obtained results showed that infertile groups (with or without leukocytospermia) had significantly lower basic semen characteristics and higher SDF, raw ORP, and static ORP (sORP) than fertile controls. The thresholds of 13% SDF (AUC = 0.733) and 1.40 sORP (AUC = 0.857) were predictive values for discriminating infertile from fertile men. In infertile groups, a higher prevalence and risk for >13% SDF and >1.40 sORP were revealed. Unexpectedly, leukocytospermic subjects had lower sORP, prevalence, and risk for >1.40 sORP than leukocytospermic-negative men. These groups did not differ in SDF and raw ORP. Both SDF and sORP negatively correlated with basic semen parameters but positively correlated with sperm head and midpiece defects. sORP positively correlated with sperm tail defects, immature sperm cells with excess residual cytoplasm, and SDF. In turn, raw ORP negatively correlated with sperm count but positively correlated with SDF and sORP. These findings indicate that (1) there is a relationship between male infertility, SDF, and OS in semen; (2) in infertile men, there is a clinically significant risk of SDF and OS irrespective of leukocytospermia; and (3) the assessment of SDF and oxidative stress should be independent of leukocytospermia.

The Role of Seminal Oxidative Stress Scavenging System in the Pathogenesis of Sperm DNA Damage in Men Exposed and Not Exposed to Genital Heat Stress.

Responding to the need for the verification of some experimental animal studies showing the involvement of oxidative stress in germ cell damage in the heat-induced testis, we investigated the possibility of a direct relationship between seminal oxidative stress markers (total antioxidant capacity, catalase activity, superoxide dismutase activity, and malondialdehyde concentration) and ejaculated sperm chromatin/DNA integrity (DNA fragmentation and chromatin condensation abnormalities) in distinct groups of men exposed and not exposed to prolonged scrotal hyperthermia. A statistical increase in the proportion of sperm with DNA fragmentation was observed in all the studied subgroups compared to the fertile men. In turn, the groups subjected to heat stress as professional drivers or infertile men with varicocele presented greater disturbances in the oxidative stress scavenging system than men not exposed to genital heat stress. Based on the comparative analysis of the studied parameters, we can conclude that alterations in the seminal oxidative stress scavenging system are directly engaged in the pathogenesis of ejaculated sperm DNA damage regardless of the intensity of the impact of thermal insult. To the best of our knowledge, this study, for the first time, revealed the co-existence of oxidative stress and sperm DNA damage in the semen of professional drivers.

Evaluation of selected semen parameters and biomarkers of male infertility - preliminary study.

Background: Because the etiopathogenesis of male infertility is multifactorial our study was designed to clarify the relationship between standard semen parameters, testicular volume, levels of reproductive hormones and the fragmentation of sperm nuclear DNA (SDF). Methods: Patients (n = 130) were clustered as subjects: 1) with an abnormal volume (utrasonography) of at least one testis (<12 mL) or with a normal volume of testes and 2) with abnormal levels of at least one of the reproductive hormones (FSH, LH, PRL, TSH, total T - electrochemiluminescence method) or with normal hormonal profiles and 3) with high level of SDF (>30%), moderate (>15-30%) or low (≤15%) (sperm chromatin dispersion test). Results: In subjects with a decreased testicular volume and in subjects with abnormal levels of reproductive hormones, decreased basic semen parameters were found. Participants with abnormal testicular volume had a higher percentage of SDF and a higher level of FSH (Mann-Whitney U test). In turn, men with a high level of SDF had lower testicular volume and conventional sperm parameters than men with a low level of SDF (Kruskal-Wallis test). Conclusions: We showed that spermatogenesis disorders coexisted with decreased testicular volume and increased FSH levels. The disorders of spermatogenesis were manifested by reduced basic sperm characteristics and a high level of sperm nuclear DNA damage.

Estrogen and Progesterone Receptor Immunoexpression in Fallopian Tubes among Postmenopausal Women Based on Time since the Last Menstrual Period.

Existing data on the expression of estrogen receptor (ERα) and progesterone receptor (PR) in fallopian tubes in postmenopausal women are mostly inconclusive. Therefore, we assessed ERα and PR immunoexpression in the oviducts of these women. One hundred postmenopausal women were divided into three groups based on time elapsed since the last menstrual period: (A) 1-5 years, (B) 6-10 years, and (C) ≥11 years. In all groups, both in the glandular epithelium and stroma of the ampulla and isthmus of the oviduct, immunolocalization of ERα and PR were noted. The glandular epithelium of the ampulla showed a higher percentage of PR-positive cells than the isthmus in each group. Regarding ERα, there were no significant differences. In the glandular epithelium in both the ampulla and isthmus, the percentage of ERα- and PR-positive cells was significantly higher than that in the stroma in each study group and higher in the A group than in the C group. In conclusion, in postmenopausal women, time elapsed since the last menstrual period in the fallopian tubes was positively correlated with the following: (1) the epithelium showed vacuolation of cytoplasm with greater frequency, (2) the proportion of ciliated cells decreased, and (3) the percentage of ERα- and PR-positive cells also decreased. The obtained results indicate a significant decrease in ERα and PR expression depending on the time that has elapsed since the last menstruation, which is undoubtedly related to the loss of the reproductive function of the patients.

Psychometric properties and longitudinal measurement invariance of the drug craving scale: Modification of the Polish version of the Penn Alcohol Craving Scale (PACS).

BACKGROUND: The Penn Alcohol Craving Scale (PACS) is an instrument with good psychometric properties that is widely used to assess alcohol craving. Based on the assumption that the experience of craving is independent of substance type, the Polish version of the PACS was modified to measure drug craving, thus creating the Penn Drug Craving Scale (PDCS). The analyses presented in the paper aim to verify the hypothesis that the PDCS has a unidimensional structure, is highly reliable and features longitudinal measurement invariance. METHODS: The research was conducted in 14 inpatient and 13 outpatient randomly selected facilities that provide psychosocial therapy to people with substance use disorder (SUD) in Poland, during June 2018 -July 2019. The data used for the analyses came from 282 patients diagnosed on the basis of ICD-10 criteria (F11.2-F19.2). The paper presents analyses with the application of: [1] confirmatory factor analysis (CFA) conducted on the basis of a polychoric correlation matrix and the WLSMV estimator; [2] a reliability estimate using Cronbach's alpha and coefficient omega; [3] verification of longitudinal measurement invariance between the beginning and end of therapy; [4] evaluation of criterion validity; [5] normalisation of the raw scores. RESULTS: The CFA results confirmed a unidimensional PDCS structure (RMSEA = 0.047, 95% CI: 0.000-0.103; CFI = 0.999; TLI = 0.999) and a high reliability of the scale (ω = 0.93). Moreover, a strict longitudinal measurement invariance of the instrument was confirmed. CONCLUSIONS: Accurate assessment of craving is possible only with valid and reliable instruments. Therefore, the psychometric properties of the PDCS were verified based on the latest statistical approaches. The scale is a valid and highly reliable tool featuring longitudinal measurement invariance and can be usefully used for research and clinical purposes. Thus, the Polish version of the PACS has been modified and successfully applied to the population of people with SUD.

Markers of Inflammation and Vascular Parameters in Selective Progesterone Receptor Modulator (Ulipristal Acetate)-Treated Uterine Fibroids.

The exact mechanism of selective progesterone receptor modulator action in leiomyoma still challenges researchers. The aim of the study was to assess the effects of ulipristal acetate (UPA) on immunoexpression of inflammatory markers and vascularization in fibroids. UPA-treated patients were divided into three groups: (1) good response (≥25% reduction in volume of fibroid), (2) weak response (insignificant volume reduction), (3) and no response to treatment (no decrease or increase in fibroid volume). The percentage of TGFß, IL6, IL10, CD117, and CD68-positive cells were significantly lower in the group with a good response to treatment vs. the control group. Moreover, the percentage of IL10 and CD68-positive cells in the group with a good response to treatment were also significantly lower compared to the no response group. Additionally, a significant decrease in the percentage of IL10-positive cells was found in the good response group vs. the weak response group. There were no statistical differences in the percentage of TNFα-positive cells and vessel parameters between all compared groups. The results of the study indicate that a good response to UPA treatment may be associated with a decrease of inflammatory markers, but it does not influence myoma vascularization.

The Negative Impact of Varicocele on Basic Semen Parameters, Sperm Nuclear DNA Dispersion and Oxidation-Reduction Potential in Semen.

Since varicocele is so common in infertile men, this study intends to analyse the relationships between varicocele and conventional semen characteristics, sperm nuclear DNA dispersion and oxidation-reduction potential (ORP) in semen. Varicocele-positive and varicocele-negative infertile men (study groups) showed significantly lower standard sperm parameters and higher sperm DNA fragmentation (SDF) and ORP in semen than healthy volunteers and subjects with proven fertility (control groups). A lower proportion of low SDF levels (0-15% SDF) and higher incidence of high SDF levels (>30% SDF), as well as a higher prevalence of high ORP values (>1.37 mV/106 sperm/mL), were found in the study groups vs. the control groups. Moreover, infertile men had significantly lower odds ratios (ORs) for low SDF levels and significantly higher ORs for high SDF levels and high ORP. SDF and ORP were negatively correlated with sperm number, morphology, motility and vitality. Furthermore, a significant positive correlation was found between SDF and ORP. The obtained results suggest that disorders of spermatogenesis may occur in varicocele-related infertility. These abnormalities are manifested not only by reduced standard semen parameters but also by decreased sperm DNA integrity and simultaneously increased oxidative stress in semen.

Alterations in fecal short chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) in men with benign prostatic hyperplasia (BPH) and metabolic syndrome (MetS).

Gut microbiome-derived short-chain fatty acids (SCFAs) emerge in the process of fermentation of polysaccharides that resist digestion (dietary fiber, resistant starch). SCFAs have a very high immunomodulatory potential and ensure local homeostasis of the intestinal epithelium, which helps maintain the intestinal barrier. We analyzed the association between stool SCFAs levels acetic acid (C 2:0), propionic acid (C 3:0), isobutyric acid (C 4:0i), butyric acid (C 4:0n), isovaleric acid (C 5:0i) valeric acid (C 5:0n), isocaproic acid (C 6:0i), and caproic acid (C 6:0n)) in aging man with benign prostatic hyperplasia (BPH) and healthy controls. The study involved 183 men (with BPH, n = 103; healthy controls, n = 80). We assessed the content of SCFAs in the stool samples of the study participants using gas chromatography. The levels of branched SCFAs (branched-chain fatty acids, BCFAs): isobutyric acid (C4:0i) (p = 0.008) and isovaleric acid (C5:0i) (p < 0.001) were significantly higher in patients with BPH than in the control group. In healthy participants isocaproic acid (C6:0i) predominated (p = 0.038). We also analyzed the relationship between stool SCFA levels and serum diagnostic parameters for MetS. We noticed a relationship between C3:0 and serum lipid parameters (mainly triglycerides) in both healthy individuals and patients with BPH with regard to MetS. Moreover we noticed relationship between C4:0i, C5:0i and C6:0i and MetS in both groups. Our research results suggest that metabolites of the intestinal microflora (SCFAs) may indicate the proper function of the intestines in aging men, and increased BCFAs levels are associated with the presence of BPH.

Hiatal hernia as a rare cause of cardiac complications - case based review of the literature.

INTRODUCTION: Hiatal hernia (HH) is a condition which refers to the protrusion of an intraabdominal organ in the thorax cavity throughan oesophageal hiatus of the diaphragm. Sliding HH is usually associated with non-specific symptoms, including heartburn, regurgitation or epigastric pain. Importantly, true paraesophageal hernia may lead to cardiac compression. Knowledge of cardiac manifestations of HH is limited. OBJECTIVE: The main aim of the study is to present the rare case of a patient with gastrothorax due to hiatal hernia which caused cardiac arrest, and to provide a literature-based review of the cardiac aspects of hiatal hernia. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: Patients with paraesophageal hernia may experience arrhythmia, including sinus tachycardia, atrial flutter, atrial fibrillation, supraventricular extrasystole and ventricular tachycardia, as well as left bundle branch block, atrioventricular conduction block and electrocardiographic changes in the ST-segment and T-wave. In echocardiograph, HH may appear as an extracardiac posterior mass encroaching on the left atrial cavity, mimicking the left atrial mass. Rarel, HH may be manifested as tension gastrothorax leading cardiac arrest. In such a case, timely diagnosis and instant adequate treatment of the underlying condition are crucial. CONCLUSIONS: Hiatal hernia should be considered as a possible cause of arrhythmia and changes in ST-T pattern, particularly if symptoms occurred after a meal. Differential diagnosis of the posterior mediastinal mass or intracardiac mass should include hiatal hernia. Gastrothorax is a rare condition associated with hiatal hernia which may lead to cardiac arrest. However, even timely recognition and therapy of gastrothorax does not ensure a positive clinical outcome.

Markers of Cellular Proliferation, Apoptosis, Estrogen/Progesterone Receptor Expression and Fibrosis in Selective Progesterone Receptor Modulator (Ulipristal Acetate)-Treated Uterine Fibroids.

There appear to be very few data on the exact mechanisms of a selective progesterone receptor modulator action in myomas. The aim of the study was to assess the effects of ulipristal acetate (UPA) on fibroids, especially on estrogen receptor (ER) and progesterone receptor (PR) immunoexpression, proliferation, apoptosis and tissue fibrosis, and to compare the above parameters in untreated (surgical attention only) and UPA-treated leiomyomas. UPA-treated patients were divided into three groups: (1) good response (≥25% reduction in volume of fibroid), (2) weak response (insignificant volume reduction) and (3) no response to treatment (no decrease or increase in fibroid volume). The study observed a significant decrease in the percentage of collagen volume fraction and ER and PR immunoexpression in the good response group, in the percentage of proliferating cell nuclear antigen (PCNA)- and Ki67-positive cells in the groups with good and weak reactions vs. control group; significantly higher apoptotic index (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells) in the good reaction group vs. control group. The results of the study indicate that a good response to UPA, manifested by a volume reduction of myoma, may be associated with a decrease in fibrosis, ER/PR and PCNA and Ki67 immunoexpression and an increase in cell apoptosis within the myoma.

The long-term effects of rapamycin-based immunosuppressive protocols on the expression of renal aquaporins 1, 2, 3 and 4 water channels in rats.

BACKGROUND: To this day, the effect of multi-drug immunosuppressive protocols on renal expression of AQPs is unknown. This study aimed to determine the influence of rapamycin-based multi-drug immunosuppressive regimens on the expression of aquaporins (AQPs) 1, 2, 3, and 4 in the rat kidney. METHODS: For 6 months, 24 male Wistar rats were administered immunosuppressants, according to the three-drug protocols used in patients after organ transplantation. The rats were divided into four groups: the control group, the TRP group (tacrolimus, rapamycin, prednisone), the CRP group (cyclosporine A, rapamycin, prednisone), and the MRP group (mycophenolate mofetil, rapamycin, prednisone). Selected red cell indices and total calcium were measured in the blood of rats and quantitative analysis of AQP1, AQP2, AQP3 and AQP4 immunoexpression in the kidneys were performed. RESULTS: In the TRP and CRP groups, a mild increase of mean corpuscular hemoglobin concentration, hematocrit and total calcium were observed. Moreover, decreased expression of AQP1-4 was found in all experimental groups, with the highest decrease in the CRP group. CONCLUSIONS: The long-term immunosuppressive treatment using multi-drug protocols decreased AQP1-4 expressions in renal tubules, possibly leading to impaired urine-concentrating ability in rat.

The Postnatal Offspring of Finasteride-Treated Male Rats Shows Hyperglycaemia, Elevated Hepatic Glycogen Storage and Altered GLUT2, IR, and AR Expression in the Liver.

BACKGROUND: A growing body of data indicates that the physiology of the liver is sex-hormone dependent, with some types of liver failure occurring more frequently in males, and some in females. In males, in physiological conditions, testosterone acts via androgen receptors (AR) to increase insulin receptor (IR) expression and glycogen synthesis, and to decrease glucose uptake controlled by liver-specific glucose transporter 2 (GLUT-2). Our previous study indicated that this mechanism may be impaired by finasteride, a popular drug used in urology and dermatology, inhibiting 5α-reductase 2, which converts testosterone (T) into dihydrotestosterone (DHT). Our research has also shown that the offspring of rats exposed to finasteride have an altered T-DHT ratio and show changes in their testes and epididymides. Therefore, the goal of this study was to assess whether the administration of finasteride had an trans-generational effect on (i) GLUT-2 dependent accumulation of glycogen in the liver, (ii) IR and AR expression in the hepatocytes of male rat offspring, (iii) a relation between serum T and DHT levels and the expression of GLUT2, IR, and AR mRNAs, (iv) a serum glucose level and it correlation with GLUT-2 mRNA. METHODS: The study was conducted on the liver (an androgen-dependent organ) from 7, 14, 21, 28, and 90-day old Wistar male rats (F1:Fin) born by females fertilized by finasteride-treated rats. The control group was the offspring (F1:Control) of untreated Wistar parents. In the histological sections of liver the Periodic Acid Schiff (PAS) staining (to visualize glycogen) and IHC (to detect GLUT-2, IR, and AR) were performed. The liver homogenates were used in qRT-PCR to assess GLUT2, IR, and AR mRNA expression. The percentage of PAS-positive glycogen areas were correlated with the immunoexpression of GLUT-2, serum levels of T and DHT were correlated with GLUT-2, IR, and AR transcript levels, and serum glucose concentration was correlated with the age of animals and with the GLUT-2 mRNA by Spearman's rank correlation coefficients. RESULTS: In each age group of F1:Fin rats, the accumulation of glycogen was elevated but did not correlate with changes in GLUT-2 expression. The levels of GLUT-2, IR, and AR transcripts and their immunoreactivity statistically significantly decreased in F1:Fin animals. In F1:Fin rats the serum levels of T and DHT negatively correlated with androgen receptor mRNA. The animals from F1:Fin group have statistically elevated level of glucose. Additionally, in adult F1:Fin rats, steatosis was observed in the liver (see Appendix A). CONCLUSIONS: It seems that treating male adult rats with finasteride causes changes in the carbohydrate metabolism in the liver of their offspring. This can lead to improper hepatic energy homeostasis or even hyperglycaemia, insulin resistance, as well as some symptoms of metabolic syndrome and liver steatosis.

Seminal Plasma Analysis of Oxidative Stress in Different Genitourinary Topographical Regions Involved in Reproductive Tract Disorders Associated with Genital Heat Stress.

The pathophysiological mechanisms responsible for male subfertility/infertility caused by or complicated by genital heat stress remains unclear in many respects. Because seminal plasma creates the environment for the proper functioning of spermatozoa, in this study, we verified the associations among standard spermiograms, seminal biochemical parameters (neutral alpha-glucosidase, fructose, and citric acid) and oxidative stress markers (total antioxidant capacity, catalase activity, superoxide dismutase activity, and malondialdehyde concentration) in distinct entities associated with male infertility with and without long-time exposure to local hyperthermia. We demonstrated that men exposed to prolonged environmental or clinically recognized local heat stress in adulthood may suffer from dysregulation of seminal antioxidant components, which can be directly associated with epididymal and prostate function. The comparative analysis of the studied parameters showed numerous correlations among all biochemical parameters (particularly neutral alpha-glucosidase) with low standard semen quality in almost all the investigated infertile groups. In light of the data obtained in this originally designed study, we conclude that more attention should be paid to the epididymis and accessory gland function in subfertile and infertile men exposed to genital heat stress, especially in the context of novel treatment algorithms (targeted therapies).

The Effects of Long-Term Immunosuppressive Therapies on the Structure of the Rat Prostate.

Background: Little is known about the overall impact of immunosuppressive drugs on the prostate. The study aimed to determine the impact of different protocols of immunosuppressive treatment on the structure of the rat ventral prostate. Methods: For 6 months, 48 male Wistar rats received immunosuppressive drugs: cyclosporin A, tacrolimus, mycophenolate mofetil, rapamycin, and prednisone, according to three-drug protocols. Light and transmission electron microscopic studies, and quantitative evaluation of immunohistochemical expression of selected intermediate filaments, CD117+ mast cells, and CD138+ plasma cells were performed in the rat ventral prostate. Results: In all experimental groups, acini focal hyperplasia, changes to the ultrastructure of the glandular epithelium, changes in the expression of cytokeratins and desmin, and numerous mast and plasma cells in the prostate stroma were found. In cyclosporine-A-based groups, atrophy and numerous intracellular vacuoles were observed. In groups where a three-drug treatment was replaced with rapamycin, morphological alterations were less severe compared to those without conversion. Conclusions: In the rat ventral prostate, (1) immunosuppressive protocols affect the morphology and immunohistochemical expression of intermediate filaments, (2) morphological alterations, expression, and localization of selected proteins are not connected with adenocarcinoma development, and (3) conversion of the treatment to rapamycin may prevent hyperplastic abnormalities.