Seminal oxidation–reduction potential as a possible indicator of impaired sperm parameters in Turkish population

Oxidative stress (OS) has been shown to have a key role in male infertility. Recently, a new measurement method has been developed to measure the overall oxidation–reduction potential (ORP) in a semen sample known as the MiOXSYS system. The aim of this study was to investigate the correlation of sperm parameters with oxidative stress levels determined by ORP and to evaluate whether the current limit is able to distinguish abnormal sperm parameters from normal ones in Turkish population. Semen samples of 121 patients who applied for infertility investigation were divided into two groups as (OS +; n:39) and (OS −; n:82). Semen parameters were compared between groups. Sperm concentration, total motility and progressive motility were found to be significantly lower in OS (+) patients compared to those OS (−), while immotile sperm count was significantly higher in OS (+) patients. Oxidative stress determined by MiOXSYS system was found to be related to reduced sperm parameters in Turkish population, which may be used as an indicator of poor sperm parameters and a support to routine semen analysis. In addition, recommended reference value was found to be reliable in distinguishing normal from impaired semen parameters.     

Correlation of oxidation reduction potential and total motile sperm count:its utility in the evaluation of male fertility potential

Oxidative stress(OS)is detri me ntal to sperm fun ctio ns,and the oxidation reductio n pote ntial(ORP)is a good measure of OS as it considers the balance betwee n oxidants and reducta nts.Total motile sperm count(TMSC)is viewed as the single most im porta nt semen analysis parameter that can predict male infertility severity,and its correlation with ORP has never been undertaken.The objectives of this study were to assess the correlation between ORP and TMSC,to identify the ORP cutoff value based on the TMSC result,and to compare this cutoff value with previously reported ORP cutoff values in literature.One thousand one hundred and sixty-eight infertile patients and 100 fertile controls were enrolled.Demographic and semen data of the participants were retrieved and analyzed.Wilcox on's rank-sum test compared variables betwee n infertile men and fertile controls;Spearman's correlation assessed the static ORP(sORP)-TMSC relationship for the whole sample and among each group individually.Using a 20×10^6TMSC threshold,receiver operator characteristic(ROC)analysis determined the sORP cutoff associated with the highest predictive values.TMSC was significantly negatively correlated with sORP across all participants(r=0.86,P<0.001),among infertile patients(r=0.729,P<0.001),and among fertile controls(r=0.53,P<0.001).A 20-million TMSC threshold determined an sORP cutoff value of 2.34 mV/106sperm/ml to be associated with 82.9%sensitivity,82.8%specificity,91.5%positive predictive value(PPV),68.5%negative predictive value(NPV),and 82.9%overall accuracy.Compared with previously reported cutoff values in searched literature,the 2.34 mV/10^6sperm/ml cutoff value identified in our study yielded the highest overall diagnostic accuracy in the evaluation of in fertile men.     

Reduced semen quality in patients with testicular cancer seminoma is associated with alterations in the expression of sperm proteins

Testicular cancer seminoma is one of the most common types of cancer among men of reproductive age.Patients with this condition usually present reduced semen quality,even before initiating cancer therapy.However,the underlying mechanisms by which testicular cancer seminoma affects male fertility are largely unknown.The aim of this study was to investigate alterations in the sperm proteome of men with seminoma undergoing sperm banking before starting cancer therapy,in comparison to healthy proven fertile men(control group).A routine semen analysis was conducted before cryopreservation of the samples(n=15 per group).Men with seminoma showed a decrease in sperm motility(P=0.019),total motile count(P=0.001),concentration(P=0.003),and total sperm count(P=0.001).Quantitative proteomic analysis identified 393 differentially expressed proteins between the study groups.Ten proteins involved in spermatogenesis,sperm function,binding of sperm to the oocyte,and fertilization were selected for validation by western blot.We confirmed the underexpression of heat shock-related 70 kDa protein 2(P=0.041),ubiquinol-cytochrome C reductase core protein 2(P=0.026),and testis-specific sodium/potassium-transporting ATPase subunit alpha-4(P=0.016),as well as the overexpression of angiotensin I converting enzyme(P=0.005)in the seminoma group.The altered expression levels of these proteins are associated with spermatogenesis dysfunction,reduced sperm kinematics and motility,failure in capacitation and fertilization.The findings of this study may explain the decrease in the fertilizing ability of men with seminoma before starting cancer therapy.     

Seasonality in human semen quality of smokers and non-smokers： effect of temperature

Aim: To analyse the possible effect of seasonal variation on semen parameters. Methods: The participants consisted of 1688 men attending the andrology laboratory between 1991 and 1997 for reduced fertility in the couple. Semen analysis was performed according to the WHO manual. The 84 individual months of the study period were each assigned to one of the three groups according to the average monthly outside temperature; Group A (temperature <4.4℃), Group B (4.4℃-13.3℃) and Group C (>13.3℃). Results: When comparing the different sperm parameters, the morphology was significantly better in Group C. However, when the smokers were analysed separately, this difference disappeared and significant seasonal variations were found in sperm density, total sperm count, motility and total motile sperm; they were deteriorated in the warmer season. In non-smokers, no such negative effect of increased temperature was observed. Conclusion: Sperm quality is influenced by seasonal factors. Increased environmental tempe     

High serum CA19-9 levels are associated with an increased risk of cholangiocarcinoma in patients with intrahepatic duct stones: a case–control study

Background

Hepatolithiasis is a known risk factor for cholangiocarcinoma (CC). Due to the high risk of complications that accompany endoscopic and surgical stone removal, it is often difficult to decide whether it is beneficial to remove intrahepatic ductal stones. We conducted a case–control study to determine the risk of developing CC and the benefit of stone removal in patients with hepatolithiasis.

Methods

Twenty-three patients with CC group between 2002 and 2012 were included in this study. For each patient with CC, four control patients with hepatolithiasis were enrolled based on age and sex matching. Finally, 115 patients with hepatolithiasis were enrolled.

Results

The mean length of time that intrahepatic stones were present was 116.57 (±98.77) months in the CC group and 80.56 (±101.10) months in the control group. History of gastrectomy [OR 5.756 (1.329–24.930), p = 0.019], history of choledochoenterostomy (OR 4.938 [1.129–21.595], p = 0.034), serum CA19-9 level [OR 1.001 (1.000–1.001), p = 0.022], and complete removal of stones [OR 0.167 (0.052–0.539), p = 0.003] were independent predictive factors of CC. In patients who had undergone incomplete removal of stones, the occurrence of CC was significantly reduced overall as well as in a subgroup of patients with elevated CA19-9 (p = 0.015 and p = 0.006, respectively) compared to patients with a CA19-9 of <22 U/mL (p = 0.477).

Conclusions

History of gastrectomy or choledochoenterostomy, high levels of serum CA19-9, and incomplete removal of stones were potential predictive factors of CC in patients with hepatolithiasis. Additionally, complete removal of stones may reduce the risk of CC in patients with high serum CA19-9 levels (>22 U/mL).     

Distribution of α- and δ-tocopherols in seminal plasma and sperm fractions of men with normal and abnormal semen parameters

The aim of this study was to investigate the presence of the different isoforms of tocopherol (T) in seminal plasma (P) and in the sperm fractions of individuals with abnormal (group 1) and normal (group 2) sperm parameters; the relationships between these isoforms and conventional sperm parameters were also explored. Two vitamin E homologues, α-T and δ-T, were identified in the semen of all participants. Although α-T and δ-T concentrations were similar in the semen of the 2 groups, group 1 showed a lower α-T ratio (S/P) (0.90 vs. 1.20, P < .001) and δ-T ratio (0.86 vs 1.13, P = .007) than group 2. In addition, both T ratios were correlated with the percentage of viable cells, detected by eosin staining. These results suggested that α-T and δ-T are not homogeneously distributed in the semen fractions; in normal semen they are more concentrated in the sperm membrane, whereas in abnormal semen the damaged sperm cells may release both Ts in the plasma. To verify whether sperm membrane breakage could alter α-T and δ-T distribution between the seminal plasma and the spermatozoa, normal sperm samples were sonicated; after sonication a consistent sperm plasma membrane fragmentation, highlighted by transmission electron microscopy, and a concomitant release of α-T and δ-T were observed. In conclusion, the Ts coupled directly with the sperm membrane seem to play the main protective role in the semen, and the release of α-T and δ-T in the P fraction is probably an index of lower antioxidant power and sperm quality.     

Assessment of quality of life in adolescent patients with orthopaedic problems: are adult measures appropriate?

New pressures of accountability brought on by a rapidly evolving system of health care financing have underscored the need for standardized, valid measures of patient outcome that reflect the effect of clinical intervention on all aspects of quality of life. In response, there has been a burgeoning interest in the area of outcomes assessment and measurement of quality of life after orthopaedic intervention in adults, but less attention has been focused on the assessment of broadly defined outcomes in children. In an effort to borrow from the broader adult experience in this area, the authors sought to examine whether the Medical Outcomes Study Short Form 36 (SF-36) or the EuroQol questionnaire, widely accepted adult health status measures, would be valid in this setting. These two measures were administered to 196 adolescent patients (10-18 years old) seeking orthopaedic evaluation. Tests of scale properties and construct validity show that these properties are maintained in this population, but neither instrument reflected known differences in health status among this cohort. Most importantly, both the SF-36 and the EuroQol exhibited serious ceiling effects (most respondents scored at the top of their scales), despite evidence indicating those patients often had suboptimal health status. Thus, neither the SF-36 nor the EuroQol is valid for use in this population. The assessment of pediatric health status demands outcomes measures specifically designed to reflect the unique needs of this population.     

Low serum pancreatic enzyme levels predict mortality and are associated with malnutrition–inflammation–atherosclerosis syndrome in patients with chronic kidney disease

Purpose

Serum levels of amylase and lipase are frequently increased in patients with chronic kidney disease (CKD). Relatively low serum pancreatic enzyme levels in CKD may represent a state of pancreatic insufficiency and may contribute to protein-energy wasting (PEW). We aimed to investigate the relationships of serum pancreatic enzyme levels with PEW, inflammation, and mortality in CKD patients.

Methods

Two hundred and thirty CKD patients (male/female: 144/86; mean age, 59 ± 16 years) were enrolled. Serum total α-amylase and lipase activities were measured by enzymatic colorimetric assays. Mean follow-up time was 18 ± 10 months. Forty-seven patients (20 %) died during this period.

Results

Serum amylase levels were increased in 95 patients (41 %) and serum lipase levels were increased in 71 patients (30 %) out of the 230 patients. Diabetic patients had significantly lower serum amylase levels than non-diabetic ones (86 ± 46 vs. 111 ± 60 IU/L, p < 0.0001). Patients with ischemic heart disease also had significantly lower serum amylase (82 ± 37 vs. 108 ± 60 IU/L, p < 0.0001) and lipase levels (39 ± 36 vs. 57 ± 57 IU/L, p = 0.007). Serum amylase and lipase levels were directly correlated with serum creatinine (r = 0.173, p = 0.009 and r = 0.374, p < 0.0001) and albumin (r = 0.410, p < 0.0001 and 0.287, p < 0.0001), and inversely correlated with CRP (r = ?0.223, p = 0.001 and r = ?0.147, p = 0.027). The Kaplan–Meier analysis revealed survival advantages for both high-amylase and high-lipase groups in end-stage renal disease (ESRD) (CKD stage 5) patients (log rank, p < 0.001 and p = 0.02, respectively). In the Cox regression analysis, serum amylase was found to be an independent predictor for mortality.

Conclusion

Serum amylase activity was found to be an independent predictor of mortality in ESRD patients. Relatively low serum pancreatic enzyme levels in CKD may be regarded as a novel component of the malnutrition–inflammation–atherosclerosis syndrome.     

Soluble TWEAK levels are independently associated with coronary artery disease severity in patients with stage 2–3 kidney disease

Purpose

Patients diagnosed with chronic kidney disease (CKD) have a greater rate of cardiovascular mortality compared with the general population. The soluble form of TNF-like weak inducer of apoptosis (TWEAK) plays a role in cellular proliferation, migration, and apoptosis. The current study aimed to analyze whether soluble TWEAK levels are associated with the severity of coronary arterial disease (CAD) in CKD patients.

Methods

Ninety-seven patients diagnosed with CKD stages 2–3 according to their estimated glomerular filtration rate and the presence of kidney injury were included in the study. Plasma sTWEAK concentrations were determined using commercially available ELISA kits. Coronary angiographies were performed through femoral artery access using the Judkins technique.

Results

Correlation analysis of sTWEAK and Gensini scores showed significant association (p < 0.01, r ² = 0.287). When patients were divided into two groups with a limit of 17 according to their Gensini score, sTWEAK levels indicated a statistically significant difference (p < 0.01).

Conclusions

Our results indicate a relationship between sTWEAK levels and CAD in CKD stages 2–3 patients.     

Cytosolic phospholipase A2 and F2 isoprostanes are involved in semen quality and human infertility—A study on leucocytospermia,varicocele and idiopathic infertility

Phospholipase A₂ (PLA₂) is involved in eicosanoid release, and F₂-isoprostanes (F₂-IsoPs), as free radical-generated eicosanoids released by PLA₂, are indicators of oxidative stress in different human conditions. This study investigated the interplay between cytosolic PLA₂ (cPLA₂), F₂-IsoPs and sperm features in male infertility, when the involvement of oxidative stress has been reported. Semen evaluation was performed following WHO guidelines, sperm ultrastructure was detected by transmission electron microscopy indicating a fertility index, and the percentages of sperm immaturity, apoptosis and necrosis. In sperm cells and seminal plasma, cPLA₂ levels were determined by immunological method, whereas F₂-IsoPs by mass spectrometry. Sperm concentration, morphology, vitality and fertility index values were significantly lower in infertile groups compared with fertile men. An increase in sperm apoptosis and necrosis (p < .01), apoptosis (p < .01) and immaturity (p < .001) was detected in leucocytospermia, idiopathic infertility and varicocele, respectively. Seminal cPLA₂ showed the highest value in varicocele group (p < .05), whereas seminal F₂-IsoPs increased in varicocele (p < .001) and leucocytospermia (p < .05) groups. In the whole population, F₂-IsoP and cPLA₂ levels were positively correlated (p < .05). On the contrary, F₂-IsoPs and cPLA₂ were not significantly different when investigated in sperm cells. Our data indicate that fatty acid oxidation/metabolism plays a role in different male reproductive pathological conditions.     

Urinary nitric oxide levels are increased and correlated with plasma concentrations in patients with Behçet's disease: Is it a new urinary activity marker?

SUMMARY: Nitric oxide (NO) is a free radical and serves many functions within the kidney. Excess NO causes glomerular injury. Behçet's disease (BD) is a systemic immunoinflammatory vasculitis, affecting every organ in the body including the kidneys (subclinic glomerulonephritis). We investigated the role of urinary total nitrite levels (end product of NO) in BD and evaluated whether urinary concentrations were correlated with its plasma levels or disease activity. Thirty‐six consecutive Behçet's patients (19 men, 17 women; 35.9 years), and 20 age‐ and sex‐matched healthy control volunteers (12 men, eight women; 33.2 years) were divided into an active (n = 16) and inactive (n = 20) period. Urinary and serum NO levels (µmol/mg urinary creatinine) were higher in BD patients (4.1 ± 0.3) than control subjects (1.7 ± 0.2; P < 0.001). Serum NO levels in Behçet's patients and control subjects were 51.3 ± 9.8 and 21.7 ± 7.3 µmol/L, respectively (P < 0.001). Active patients had higher urinary NO excretion (4.9 ± 0.3) than inactive patients (3.3 ± 0.3; P < 0.01). Urinary NO levels were correlated with its serum levels (r² = 0.69, P < 0.001). Higher urinary NO levels found in BD may be produced by the kidney as a result of an inflammatory stimulation. As excess NO is toxic to the tissues, increased NO levels may play a role in mediating subclinic glomerular injury of such patients. However, we could not determine the exact site(s) of NO synthesis by the kidney, such as the glomeruli, blood vessels and/or the tubular cells. Whatever the source, urinary NO levels may be used as a new activity marker in the diagnosis and follow up of BD by serial measurements.     

High expression of karyopherin-α2 defines poor prognosis in non-muscle-invasive bladder cancer and in patients with invasive bladder cancer undergoing radical cystectomy

Background

Conventional clinicopathologic risk factors have failed to accurately predict the prognosis of patients with bladder cancer (BC).

Objective

To evaluate karyopherin-α2 (KPNA2) expression as a progression marker in patients with non–muscle-invasive BC (NMIBC) treated by conservative methods and as a prognostic marker in patients with invasive BC undergoing radical cystectomy (RC).

Design, setting, and participants

Two different tissue microarrays were constructed, one with 234 primary Ta/T1 tumours from patients treated by transurethral resection of the bladder and one with 377 tumours from RC patients.

Intervention

KPNA2 expression based on immunohistochemistry.

Measurements

Risk of progression of Ta/T1 patients to muscle-invasive BC was estimated in clinical follow-up to progression or a minimum of 53 mo. Risk of recurrent disease and death following RC was estimated in clinical follow-up of a minimum of 24 mo in patients alive.

Results and limitations

A high KPNA2 expression in Ta/T1 patients was significantly correlated with a higher risk of progression that was independent of conventional risk factors in multivariate analysis. In patients undergoing RC, a high KPNA2 expression was an independent predictor of poor prognosis. A high KPNA2 expression was correlated with a higher risk of visceral metastasis rather than lymphatic spread.

Conclusions

KPNA2 expression is a marker for progression of NMIBC and a prognostic marker in patients undergoing RC.     

The change in Thiol–Disulphide Homeostasis levels as an oxidative stress marker after varicocelectomy: Is there a relationship with sperm parameters?

One of the most important causes of varicocele-related infertility is oxidative stress (OS). One of the markers considered as an indicator of OS is thiol–disulphide homeostasis (TDH). Based on the hypothesis that OS should decrease after varicocelectomy in the light of this information, in our current study, we investigated the relationship between TDH levels and sperm parameters. The data of 56 infertile varicocele men were prospectively analysed. The post-operative total and native thiol levels were significantly higher than those pre-operative total and native thiol levels (477.7 & 436.7 nmol/L, 417.6 & 372.1 nmol/L). Positive correlation was found between total thiol change and change in semen volume (ρ: .277, p: .039), ratio of spermatozoa with normal morphology (ρ: .342, p: .01), progressive (ρ: .334, p: .012) and nonprogressive motility (ρ: .385, p: .003). Positive correlation was also found between native thiol change and semen volume (ρ: .349, p: .008), ratio of spermatozoa with normal morphology (ρ: .362, p: .006), progressive (ρ: .297, p: .026) and nonprogressive motility (ρ: .368, p: .005). Change in the level of TDH was found as positively correlated with progressive and nonprogressive motility change. According to these results, OS decreases with varicocelectomy in infertile patients and TDH can be used as a useful method for measuring OS.     

Nutritional status is associated with health-related quality of life in children with cystic fibrosis aged 9–19 years

BackgroundThe impact of improved nutritional status on health-related quality of life (HRQOL) is unknown for children with cystic fibrosis (CF).MethodsAssociations between nutritional status and HRQOL were examined over 2 years in 95 children, aged 9–19 years, who were followed in the Wisconsin Newborn Screening Project. HRQOL was assessed using the Cystic Fibrosis Questionnaire (CFQ). Associations between height z-score (HtZ), BMI z-score (BMIZ) and seven CFQ dimensions were evaluated.ResultsMean values of at least 80 were observed for all CFQ dimensions except respiratory symptoms and treatment burden. Treatment burden was significantly worse in patients with meconium ileus (57) compared to pancreatic insufficient (65) and sufficient (78) subjects, p < 0.0001. HtZ and BMIZ were positively associated with physical functioning and body image (p < 0.05).ConclusionsBetter nutritional status was associated with increased HRQOL scores. Early diagnosis through newborn screening and improved nutrition provides an opportunity to enhance quality of life and body image perception.     

High serum levels of a non-(1–84) parathyroid hormone (PTH) fragment in pediatric haemodialysis patients

The measurement of serum intact parathyroid hormone (PTH) is routinely made in haemodialysed (HD) patients to diagnose and monitor secondary hyperparathyroidism. We measured pre- and post-dialysis serum ionized calcium (Ca²⁺) and PTH in 12 HD children (7 boys) aged 13.8±3.6 years. A group of 27 normal short-statured children served as controls. Serum PTH was assessed by a new assay (CAP) recognizing only the (1–84) molecule and an older one (Allegro) recognizing both the 1–84 and a non-(1–84) PTH equally. The concentrations obtained with the CAP assay were lower than those obtained with the Allegro assay both in controls and in HD patients. They were still lower in HD patients when expressed as multiples of the median of the control group. The Allegro/CAP ratio, was highly variable from one subject to another and was lower (P<0.0001) in controls (1.46±0.26) than in HD patients, both before (3.06±1.60) and after dialysis (2.94±0.65). During dialysis, Ca²⁺ increased significantly (P<0.0001) and PTH decreased significantly (P<0.0001) with both the CAP and the Allegro assays, but was more often normal or low with the CAP than with the Allegro assay. Although the two assays correlate well, they may provide different clinical information in some HD children which could lead to different therapeutic decisions. Received: 13 March 2001 / Revised: 12 July 2001 / Accepted: 12 July 2001     

Age–period–cohort effects in the incidence of hip fractures: political and economic events are coincident with changes in risk

Summary

An age–period cohort model was fitted to analyse time effects on hip fracture incidence rates by sex (Portugal, 2000–2008). Rates increased exponentially with age (age effect). Incidence rates decreased after 2004 for women and were random for men (period effect). New but comprehensive fluctuations in risk were coincident with major political/economic changes (cohort effect).

Introduction

Healthcare improvements have allowed prevention but have also increased life expectancy, resulting in more people being at risk. Our aim was to analyse the separate effects of age, period and cohort on incidence rates by sex in Portugal, 2000–2008.

Methods

From the National Hospital Discharge Register, we selected admissions (aged ≥49 years) with hip fractures (ICD9-CM, codes 820.x) caused by low/moderate trauma (falls from standing height or less), readmissions and bone cancer cases. We calculated person-years at risk using population data from Statistics Portugal. To identify period and cohort effects for all ages, we used an age–period–cohort model (1-year intervals) followed by generalised additive models with a negative binomial distribution of the observed incidence rates of hip fractures.

Results

There were 77,083 hospital admissions (77.4 % women). Incidence rates increased exponentially with age for both sexes (age effect). Incidence rates fell after 2004 for women and were random for men (period effect). There was a general cohort effect similar in both sexes; risk of hip fracture altered from an increasing trend for those born before 1930 to a decreasing trend following that year. Risk alterations (not statistically significant) coincident with major political and economic change in the history of Portugal were observed around birth cohorts 1920 (stable–increasing), 1940 (decreasing–increasing) and 1950 (increasing–decreasing only among women).

Conclusions

Hip fracture risk was higher for those born during major economically/politically unstable periods. Although bone quality reflects lifetime exposure, conditions at birth may determine future risk for hip fractures.