Do estrogens regulate lipid status in testicular steroidogenic Leydig cell?

In this study mouse Leydig cell (MA-10) were treated with G-protein coupled membrane estrogen receptor antagonist (G-15; 10 nM). Cells were analyzed by Western blotting for expression of estrogen-related receptors (ERRα, ß and γ), steroidogenic markers (lutropin receptor; LHR and 3ß-hydroxysteroid dehydrogenase; 3ß-HSD) and lipid droplet markers (perilipin; PLIN and microtubule-associated protein 1 A/1B-light chain 3; LC3). Concomitantly, microscopic analyses by light microscope (immunofluorescent staining for lipid droplets, PLIN and LC3) as well as by electron microscope (for lipid droplet ultrastructure) were utilized. For analysis of cholesterol content, cAMP level and progesterone secretion, G-15, estrogen receptor (ER) antagonist (ICI 182,780; 10 µM), 17ß-estradiol (10 mM) and, bisphenol A (BPA; 10 nM) were used alone or in combinations. We revealed no changes in ERRs expression but alterations in ERRß and γ localization in G-15-treated cells when compared to control. Partial translocation of ERRß and γ from the cell nucleus to cytoplasm was observed. Decreased expression of LHR, 3ß-HSD, PLIN and LC3 was detected. Moreover, in treated cells large lipid droplets and differences in their distribution were found. Very strong signal of co-localization for PLIN and LC3 was found in treated cells when compared to control. In ultrastructure of treated cells, degenerating lipid droplets and double membrane indicating on presence of lipophagosome were observed. We found, that only (i) BPA and G-15 did not effect on cholesterol content, (ii) BPA, G-15 and ICI did not effect on cAMP level and (iii) BPA, ICI alone and in combination, and BPA with G-15 did not modulate progesterone secretion. These findings showed complex and diverse estrogen effects on mouse Leydig cells at various steps of steroid hormone production (cholesterol storage, release and processing). Lipid homeostasis and metabolism in these cells were affected by endogenous and exogenous estrogen, interactions of receptors (GPER, ER and ERR) and GPER and ER antagonists.

Major depression and atrial natriuretic peptide: The role of adverse childhood experiences.

Atrial natriuretic peptide (ANP) exerts anxiolytic effects in animals and humans. Patients with anxiety, trauma-associated and depressive disorders exhibit lower ANP plasma levels compared to healthy individuals. However, the role of ANP in patients with major depressive disorder (MDD) with and without concomitant adverse childhood experiences (ACE) and in healthy individuals with and without ACE is not clear. We recruited a total of 93 women: 23 women with MDD and ACE, 24 women with MDD without ACE, 22 women with ACE but no current or lifetime MDD, and 24 healthy women without ACE. ANP plasma levels were measured with a radioimmunoassay. The four groups did not differ in demographic and clinical variables. We found a positive correlation between age and plasma levels of ANP (r = .39; p < .001). After controlling for age, there was no significant main effect of MDD or ACE on ANP plasma levels, but a significant interaction between MDD and ACE such that ACE was associated with reduced basal ANP levels in the absence of MDD. We assume that low plasma ANP might be a consequence of ACE in the absence of current psychopathology. Therefore, future studies are needed to replicate our findings and to characterize the influencing factors of ACE on ANP more comprehensively, for example by including a comprehensive trauma and comorbidity anamnesis as well as cardiovascular state and risk factors.

Prenatal exposure to an environmentally relevant mixture of Canadian Arctic contaminants decreases male reproductive function in an aging rat model.

Elevated levels of organochlorines (OC) have been reported in Inuit populations in the Arctic. We hypothesized that prenatal exposure to a Canadian Arctic OC mixture adversely affects male reproductive function and health with age. Sprague-Dawley female rats (F0) were gavaged with an environmentally relevant concentration of an Arctic OC mixture or corn oil (Control) during mating with untreated males until parturition (F1 litters). After postnatal day (PND) 90, the weights of the OC F1 males differed dramatically relative to Controls (P<0.05; n=10) and they exhibited respiratory distress. Except for possible thinning of the alveolar barrier, histological observation of the lungs revealed no apparent pathology to explain the respiratory distress. At PND 365, OC F1 males had reduced relative reproductive organ weights and lower sperm quality than Controls (P<0.05). At PND 90, OC F1 males were subfertile (P<0.05), but were infertile at PND 365. In conclusion, environmentally relevant prenatal OC exposure reduced reproductive function and health in aging male rats, providing new insight into the effects of early-life exposures to these contaminants.

Dynamics of core body temperature cycles in long-term measurements under real life conditions in women.

Studies under real life conditions become more and more relevant in chronobiological and chronomedical research. The present study aims to analyze one of the most prominent biological rhythms: the core body temperature (CBT) rhythm in the real world outside the laboratory. CBT was recorded continuously in 37 healthy women (age between 21 and 44 years, median 29 years) with a newly developed intravaginal temperature sensor for up to 102 days. Sleep logs were available from 23 participants. To quantify the daily dynamics of each individual CBT-curve, novel measurement parameters are introduced which permit the quantification of the phase and shape of the CBT rhythms as well as their relation to the sleep-wake cycle. In addition to the classical phase markers (i.e. nadir and peak), the daily curves were segmented into quartiles by introducing the t25/t50/t75-values which can be used as phase and shape markers. At variance to previous studies, a conspicuous day-to-day variation was shown not only for the time point of the peak, but also for the time point of the nadir. However, the t-values, particularly the t75-value were relatively closely locked to external time and thus represent more reliable phase markers than the nadir. The (variable) time point of the nadir determined the period length, phase and shape of the subsequent CBT cycle. If a nadir occurred close to the wake-up time, the following cycle was considerably shorter than 24 hours, while a nadir distant from the wake-up time was followed by a longer cycle. Thus, the period lengths of the daily CBT cycles of each individual were characterized by an "expand/contract" rhythm. The analyses of the novel phase markers (t25/t50/t75) of the CBT curves allowed to identify "early" and "late" participants who may differ in their phase-response curves with regard to the entraining effect of light. In addition, the novel phase markers mirrored the different social entrainment conditions on weekends and workdays.

HRV Influence During Renal Transplantation Procedure on Long-Term Mortality.

BACKGROUND: The autonomic nervous system plays an important role in heart function regulation. One of the most acknowledged methods for noninvasive measurement of autonomic system activity is to determine heart rate variability (HRV). Reduced HRV parameters-heart rate rigidity/stiffness-are an independent prognostic factor of sudden cardiac death risk because of arrhythmia. Renal transplantation is an important factor in HRV changes because of hemodynamic and ion disturbances. The main purpose of this study was to determine the influence of HRV disturbances during renal transplantation procedures on long-term mortality in patients with chronic kidney disease. METHODS: A prospective observation study was performed in the Department of Anesthesiology, Intensive Care, and Acute Poisoning, Pomeranian Medical University, Szczecin, Poland. There were 75 patients (mean age, 47 ± 12 years; 42 men) treated with renal transplantation between 2008 and 2010. Patients were monitored with electrocardiographic tracing with the use of 7 electrodes in position type B. The final stage of analysis was to determine the possible relationship between HRV parameters during the perioperative period and the number of deaths within a 5-year follow-up. RESULTS: HRV parameters during the perioperative period of renal transplantation and the number of deaths within a 5-year follow-up, measured by use of the Holter method, did not differ among patients in the studied population. CONCLUSIONS: HRV is a noninvasive and confirmed tool used for the evaluation of autonomic function and mortality risk in patients with end-stage renal disease. HRV parameters recorded in the perioperative period are not optimal stratification tools for estimating the risk of cardiac deaths in patients with end-stage renal disease.

Spatial differences of matrix metalloproteinase-2 and matrix metalloproteinase-9 within abdominal aortic aneurysm wall and intraluminal thrombus.

Formation of an abdominal aortic aneurysm is a complex process involving aortic wall degradation. The matrix metalloproteinases (MMPs) mainly involved in this process are MMP-2 and MMP-9. Most aneurysms contain an intraluminal thrombus. It is suggested that the thrombus' thickness correlates with the risk of aneurysm rupture and may be a new prognostic factor. The purpose of the present study was to investigate enzyme protein levels in thick (A1) and thin (B1) segments of the thrombus and aneurysm wall sections A (adjacent to A1) and B (adjacent to B1). Aneurysm samples from one aneurism sac were collected from 36 patients that underwent aneurysm repair. MMP-2, MMP-9 and a tissue inhibitor of metalloproteinases (TIMP-1) were measured using enzyme-linked-immunosorbent assay of protein extract. MMP-9 concentrations were significantly higher in B1 samples compared with A1 (113.4 ± 118.0 versus 63.0 ± 61.2, P = 0.004), A(113.4 ± 118.0 versus 31.7 ± 30.0, P < 0.001) or B (113.4 ± 118.0 versus 39.5 ± 41.5, P < 0.001). Likewise MMP-9/TIMP-1 ratio was elevated in B1 compared with A1 (18.9 ± 27.8 versus 9.1 ± 10.6, P = 0.017), A (18.9 ± 27.8 versus 2.5 ± 2.2, P < 0.001) or B (18.9 ± 27.8 versus 3.6 ± 4.5, P < 0.001). MMP-2 and TIMP-1 were higher in A compared with A1 (18.4 ± 8.5 versus 7.2 ± 7.6, P < 0.001; 14.3 ± 5.9 versus 8.5 ± 5.4, P < 0.001, respectively) and B1 (18.4 ± 8.5 versus 5.2 ± 2.9, P < 0.001; 14.3 ± 5.9 versus 8.9 ± 4.9, P < 0.001, respectively) as well as in B compared with A1 (15.9 ± 7.3 versus 7.2 ± 7.6, P < 0.001; 13.0 ± 5.0 versus 8.5 ± 5.4, P < 0.001, respectively) and B1 (15.9 ± 7.3 versus 5.2 ± 2.9, P < 0.001; 13.0 ± 5.0 versus 8.9 ± 4.9, P = 0.003, respectively). There were significant correlations between thin thrombus TIMP-1 and thrombus thickness (ß = -0.24, P = 0.021) and between thin thrombus MMP-9/TIMP-1 ratio and thrombus thickness (ß = 1.75, P = 0.003). Our study has revealed that the presence of thrombi with thin segments in the aneurysm sac, associated with higher proteolytic activity, could possibly be used as a potential indicator of a rupture site.

THE GSTP1 c.313A>G POLYMORPHISM MODULATES THE CARDIORESPIRATORY RESPONSE TO AEROBIC TRAINING.

The GSTP1 c.313A>G polymorphism is a candidate to explain some of the individual differences in cardiorespiratory fitness phenotypes' responses to aerobic exercise training. We aim to explore the association between the GSTP1 c.313A>G polymorphism and the response to low-high impact aerobic exercise training. Sixty-six Polish Caucasian women were genotyped for the GSTP1 c.313A>G polymorphism; 62 of them completed 12-week aerobic (50-75% HRmax) exercise training and were measured for selected somatic features (body mass and BMI) and cardiorespiratory fitness indices - maximal oxygen uptake (VO2max, maximum heart rate (HRmax), maximum ventilation (VEmax) and anaerobic threshold (AT) - before and after the training period. Two-factor analysis of variance revealed a main training effect for body mass reduction (p=0.007) and BMI reduction (p=0.013), improvements of absolute and relative VO2max (both p<0.001), and increased VEmax (p=0.005), but not for changes in fat-free mass (FFM) (p=0.162). However, a significant training x GSTP1 c.313A>G interaction was found only for FFM (p=0.042), absolute and relative VO2max (p=0.029 and p=0.026), and VEmax (p=0.005). As the result of training, significantly greater improvements in VO2max, VEmax and FFM were gained by the GG+GA group compared to the AA genotype group. The results support the hypothesis that heterogeneity in individual response to training stimuli is at least in part determined by genetics, and GSTP1 c.313A>G may be considered as one (of what appear to be many) target polymorphisms to influence these changes.

Influence of the hemodynamic status of multiorgan donors on long-term kidney graft survival--a multivariable analysis.

BACKGROUND: The quality of transplanted organ and timing of the initiation of its effective function depends on many factors potentially causing graft dysfunction. The aim of this study was to evaluate the influence of the cardiovascular status of multiorgan donors on the long-term kidney graft survival over a 15-year observation period. METHODS: In 2007, the authors of this study published a multicenter prospective study evaluating the influence of the hemodynamic status of multiorgan donors on the early function of transplanted kidney. The results of that study showed that mean arterial pressure, central venous pressure, and pulmonary capillary wedge pressure values of the donor importantly influence the frequency of delayed graft function after renal transplantation. The present analysis covers the effect of the donor's hemodynamic status parameters on graft function time within the 15-year observation period. Univariate and multivariate analyses using the Cox regression proportional hazard model were performed to evaluate the prognostic parameters for overall survival and renal graft survival time. P < .05 was considered to be significant. RESULTS: The univariate analysis showed a significantly shorter time of graft survival in the group of recipients who had a kidney retrieved from donors with lower pulmonary capillary wedge pressure values (P = .038) and lower cardiac index values (P = .039). The same results were obtained for the multifactorial Cox logistic regression analysis. CONCLUSIONS: The filling of the intravascular bed of the donor as determined by pulmonary capillary wedge pressure and maintained donor tissue perfusion as determined by cardiac index, impose important factors influencing long-term kidney graft survival.

Influence of selected factors on long-term kidney graft survival--a multivariable analysis.

BACKGROUND: Long-term function of transplanted kidney is the factor determining quality of life for transplant recipients. The aim of this study was to evaluate the effect of selected factors on time of graft function after renal transplantation within 15 years of observation. METHODS: Preoperative and intraoperative factors were analyzed in 232 kidney recipients within a 15-year observation period. Analysis included age, sex, cause of recipient's renal failure, length of hemodialyses before transplantation, peak panel reactive antibodies test, human leukocyte antigen compatibility, cold ischemia time, delayed graft function occurrence, length and time of hemodialyses after transplantation, early graft rejection, creatinine level at days 1, 3, 7, 30, 90, and 180 after transplantation, and influence of these factors on the time of graft function. Statistical analysis was performed with the use of univariate and multivariate Kaplan-Meier test and Cox regression proportional hazards model, with P < .05 considered to be significant. RESULTS: Univariate analysis showed significantly shorter renal graft function in the group of recipients with higher creatinine levels in all of the analyzed time periods and in patients experiencing delayed graft function. Length of time of hemodialyses after transplantation and number of dialyses had significant impact on worsening of late transplant results. Multivariate analysis reported that early graft rejection in the postoperative period is an independent factor improving late graft function: P = .002; hazard ratio (HR), 0.49 (95% confidence interval [CI], 0.31-0.78). Higher creatinine level at day 90 after kidney transplantation is a predictive factor of late graft dysfunction: P = .002; HR, 1.68 (95% CI 1.2-2.35). CONCLUSIONS: Creatinine level at day 90 after renal transplantation is the prognostic factor of long-term kidney function. Early transplant rejection leads to introduction of more aggressive immunosuppression protocol, which improves long-term transplant results.

Effect of recipient sensitization (peak panel reactive antibodies) on 15-year survival after kidney transplantation.

BACKGROUND: Despite dynamic development within the field of transplantology, the immunization of a potential organ recipient remains an important issue for transplant teams. Panel reactive antibodies (PRA) identification in the serum of the recipient remains routine practice in the majority of transplantation centers. The influence of peak PRA levels on graft function is a well known fact. The aim of this study was to determine the effect of peak PRA on long-term survival after renal transplantation. METHODS: The study was conducted on a group of 232 kidney recipients from multiorgan donors, transplanted in 6 transplant centers in Poland from 1995 to 1997. Data analyzed in this study included recipients' age, sex, PRA, HLA, number and time of hemodialyses after the transplantation, cold ischemia time, and etiology of end-stage renal disease. The effect of data examined in this study on mortality was evaluated at set time points at 5, 10, and 15 years after transplantation. The statistical methods included monofactorial and multifactorial Kaplan-Meier survival analysis and Cox proportional hazards model for mortality prediction. A P value of <.05 was considered to be statistically significant. RESULTS: Among all of the analyzed factors, only peak PRA concentrations significantly correlated with increased mortality among renal transplant recipients. The results were analyzed in all of the set time points: P = .007 at 5 years, P = .014 at 10 years, and P = .05 at 15 years after transplantation. CONCLUSIONS: The increased level of PRA in kidney recipients is a risk factor increasing mortality after the transplantation.

Impact of graft infection on long-term survival after kidney transplant.

BACKGROUND: Patients undergoing transplantation procedures are at a high risk of developing infections because of the need for immunosuppression. Infections presenting directly after renal transplantation greatly influence the overall success of the procedure. The aim of this study was to evaluate the influence of postoperative infection on the length of survival after renal transplant. METHODS: In 2009 a multicenter prospective trial evaluating the factors that influence the occurrence of postoperative infective complications was published by the authors. That study reported that 25 out of 232 recipients of a renal transplant were diagnosed with an infection. The present study shows the effect of postoperative infection on the length of survival after renal transplantation during a 15-year observation period. Statistical methods involved monofactorial and multifactorial Kaplan-Meier analysis for the length of survival and the Cox proportional hazards model for mortality prediction. A P value of <.05 was considered to indicate statistical significance. RESULTS: The analysis demonstrated that the lifespan of renal transplant recipients was decreased in those with postoperative infection, at both year 10 of the observation period (P = .013) and 15 years after transplantation (P = .012). Moreover, it was ascertained that an infection in the postoperative period was an independent risk factor increasing the mortality after renal transplantation: P = .026; hazard ratio 2.90 (95% confidence interval, 1.13-7.41). CONCLUSIONS: The occurrence of an infection in the postoperative period significantly decreases the lifespan of a renal transplantation recipient.

Does the A9285G Polymorphism in Collagen Type XII α1 Gene Associate with the Risk of Anterior Cruciate Ligament Ruptures?

One of the most severe injuries sustained by athletes is rupture of the anterior cruciate ligament (ACL). Recent investigations suggest that a predisposition for ACL rupture may be the result of specific genetic sequence variants. In light of this, we decided to investigate whether the COL12A1 A9285G polymorphism was associated with ACL ruptures in Polish football players. We compared genotypic and allelic frequencies of the COL12A1 A9285G polymorphism in two groups of athletes: 91 male football players (23 ± 3 years) with surgically diagnosed primary ACL ruptures who qualified for ligament reconstruction (cases) and 143 apparently healthy, male football players of the same ethnicity, a similar age category, and a comparable level of exposure to ACL injury, who were without any self-reported history of ligament or tendon injury (controls). DNA samples extracted from the oral epithelial cells were genotyped by using a real-time polymerase chain reaction (Ri-Ti-PCR) method. The genotype distribution in the cases were not different from those in controls (p = 0.70). The frequency of the G allele was lower in the cases (18.1%) but not statistically significant (p = 0.40) when compared with controls (21.3%). Our results are in contradiction to the hypothesis that the COL12A1 A9285G polymorphism is associated with a predisposition for ACL injury. However, these conclusions should be supported with more experimental studies on COL12A1 polymorphisms.

MBL2, MASP2, AMELX, and ENAM gene polymorphisms and dental caries in Polish children.

OBJECTIVE: The aim of the study was to examine whether the MBL2 C(-290)G and G161A, MASP2 A359G, AMELX C287T and C522T, and ENAM C2452T polymorphisms are associated with dental caries. SUBJECTS AND METHODS: Genomic DNA of 95 Polish children with 'higher caries experience' (HC) and 84 subjects with 'lower caries experience' (LC) belonging to two age-groups (5 and 13 years old) was extracted from the buccal mucosa. SNPs were genotyped with PCR-RFLP methods. RESULTS: Among 5-year-old children, we found significantly higher percentage of subjects carrying MBL2 (-290)G allele in HC group compared with LC group (43.2%vs 17.6%, P = 0.023). MBL2 C(-290)G-G161A C-G haplotype was overrepresented in LC group in 5-year-olds (P = 0.01), while the opposite association was observed in 13-year-olds, where C-G was overrepresented in HC group (P = 0.028). In 5-year-old children, the frequency of MBL2 G-G haplotype was higher in HC group compared with LC subjects (P = 0.045), while the opposite association (with borderline significance) was observed in 13-year-old children (P = 0.057). SNPs in MASP2, AMELX, and ENAM were not associated with dental caries. CONCLUSION: MBL2 gene polymorphism is associated with caries experience in Polish children, but the direction of this association seems to be opposite in primary and permanent dentition.

Possible counter effect in newborns of 1936A>G (I646V) polymorphism in the AKAP10 gene encoding A-kinase-anchoring protein 10.

OBJECTIVE: Cyclic adenosine monophosphate/protein kinase A (PKA) is important in embryonic development. The human AKAP10 gene is polymorphic: 1936A>G results in changes to a PKA-binding domain and increased targeting to mitochondria. Previous studies found G1936 as 'deleterious' in adults, and this study investigates whether this holds true in preterm birth. STUDY DESIGN: Study group consisted of 80 preterm newborns (PTNs) born before the 38th gestation week. Control group consisted of 123 full-term healthy newborns born after the 37th gestation week with uncomplicated pregnancies. Genomic DNA was extracted from umbilical blood and AKAP10 genotypes were identified by PCR/restriction enzyme. RESULT: Significant differences in frequencies of 1936A>G genotypes/alleles between both groups were found. PTNs had increased frequency (55%) of AA homozygotes (odds ratio, AA versus AG+GG: 2.63 (95% confidence interval: 1.33 to 5.20), P=0.006) after adjustments: mothers with previous PTNs, smoking, first pregnancy, first delivery and Cesarean section. CONCLUSION: Results suggest G1936 is preventative factor against preterm birth, in contrast with previously asserted negative effects in adults.

The effect of cause of cadaveric kidney donors death on fibrinolysis and blood coagulation processes.

BACKGROUND: Organ donors can be generally divided into two groups according to the cause of their death. The first group is composed of those who died because of physical injuries, especially road traffic injury, and the second group, those who died from central nervous system (CNS) stroke or bleeding. The aim of our work was to examine hemostatic processes among kidney donors. MATERIALS AND METHODS: The 38 deceased kidney donors (KD) included 11 women and 27 men of overall average age of 37±12 years. The donor group of according to the cause of death, included 14 injured donors (ID) (41%) and 24 noninjured donors (ND) donors (59%). The control group consisted of 25 healthy volunteers matched for sex and age. We determined the following concentrations: antithrombin (AT), thrombin/antithrombin complexes (TAT), and prothrombin F1+2 fragments. The fibrinolytic parameter concentrations were: plasminogen (PL), plasmin/antiplasmin complexes (PAP), and D-dimers. RESULTS: Deceased kidney donors showed an increased plasma concentrations of TAT complexes (P<.000001) and prothrombin fragments F1+2 (P<.0000001); however, the protein C concentration was decreased (P<.000001). The antithrombin activity was similar to the control group. The concentrations of PAP complexes and d-dimers were higher (both P<.000001), but the level of PL lower among KD compared with controls (P<.0000001). The higher of TAT, PAP complexes, d-dimers, and F1+2 concentrations as well and as lower plasminogen and PC concentrations were evidence for increased activation of blood coagulation and fibrinolysis in cadaveric KD. However, analysis compairing ID versus ND donors revealed increased concentrations of PAP complexes (P<.05) and decreased amounts of TAT complexes (P<.01) among ID subgroup. The positive predictive value (PPV) and negative (NPV) for PAP complexes were 75% and 68% and for TAT, 71% and 57%, respectively. On the basis of these observations, we concluded that an intensive activation of fibrinolytic process occurs among the ID. In contrast, ND show intensive activation of blood coagulation.

Donor-recipient gender mismatch affects early graft loss after kidney transplantation.

BACKGROUND: We sought to determine the risk factors influencing the occurrence of early graft loss among kidney transplant recipients. STUDY DESIGN: One hundred forty-six potential donors and 230 kidney recipients were included in the study. Prior to organ procurement we collected demographic data as well as hemodynamic data of mean arterial pressure, central venous pressure, pulmonary capillary wedge pressure, systemic vascular resistance index acquired by means of a thermodilution method. The recipient data included age, gender, prior hemodialysis period, panel-reactive antibodies, cold ischemia time, renal insufficiency cause, and donor-recipient gender mismatch. We assessed the influence of the data on graft loss at 30 days after renal transplantation. To confirm the relationships, we performed statistical analyses using chi-square, Fisher exact, and V. Cramer tests. RESULTS: There were no significant relationships between the analyzed parameters and early graft loss in the study group except for gender mismatch. The 71 female recipients of male kidneys showed the lowest graft survival: donor/recipient male/female 89%; donor/recipient female/male 97%; no mismatch 97% (P=.01). CONCLUSIONS: Female recipients of male kidneys may experience a greater risk of early graft loss compared with all other gender combinations.

Association of rs10918594 polymorphisms of nitric oxide synthase 1 adaptor protein (NOS1AP) with QTc interval prolongation during kidney transplantation.

BACKGROUND: The mechanisms of sudden cardiac death are difficult to recognize, but repolarization disturbances have been shown to be the cause. The purpose of this study was to investigate whether the polymorphism of nitric oxide synthase 1 adaptor protein (NOS1AP) was related to the risk of occurrence of corrected QTc-interval prolongation and ventricular arrhythmias recorded on electrocardiography (ECG) Holter monitoring in kidney transplant recipients. STUDY DESIGN: The 75 adult first kidney transplant patients included 43 men with an overall mean age of 45±12 years (range, 20-68). Additional patient monitoring during the procedure and in the postoperative period consisted of a continuous ECG tracing recording and investigation of the rs10918594 NOS1AP polymorphism. RESULTS: We observed Transient QTc-interval prolongation during the perioperative period. NOS1AP genotypes were in Hardy-Weinberg equilibrium. For further statistical analysis, we combined GG homozygotes and CG heterozygotes because of the small numbers available; therefore, only a dominant mode of inheritance was investigated. There were no gender differences in QTc-interval patterns. Analysis of variance with repeated measures revealed no interaction between NOS1AP and QTc-interval values taken at various times among the kidney recipients. CONCLUSIONS: The transplantation procedure may lead to dynamic repolarization disturbances, which may produce an increased risk of severe arrhythmias despite optimization of patient status. The NOS1AP rs203462 polymorphisms did not correlate with an increased risk of QT interval prolongation among kidney recipients.

Graft infection in kidney recipients and its relation to transplanted kidney function.

INTRODUCTION: Following kidney transplantation, septic complications are the leading causes of therapeutic failure including recipient death or graft removal. The serum creatinine level is one of the earliest metrics of kidney metabolic function. We examined the influence of graft infection on serum creatinine levels in kidney recipients. STUDY DESIGN: We analyzed the function of 220 kidneys transplanted in nine centers in Poland. The kidneys were recovered from 146 multiorgan donors. Donor urea and creatinine levels were within the normal range. We investigated the influence of perioperative graft infection incidence on recipient creatinine levels at 1, 2, 3, 7, 14, 30, 90, and 180 days after kidney transplantation. The association of the serum creatinine level with categorical variables was assessed using either Student t test analysis of variance and multivariate techniques. In all analyses P<.05 indicated statistical significance. RESULTS: There were 25 graft infections revealing a significant relationship with increased recipient serum creatinine level after kidney transplantation (P=.003). Multivariate analysis confirmed the impact of infection. CONCLUSION: Perioperative kidney graft infection influenced graft funtion in the early and late periods post-transplantation.

The outcomes of treatment and the etiology of lymphoceles with a focus on hemostasis in kidney recipients: a preliminary report.

BACKGROUND: The etiopathogenesis of lymphoceles remains incompletely understood. The aim of our work was to analyze the perturbations of blood coagulation process for their possible impact on the etiology of lymphoceles. Additionally we performed an evaluation of the incidence and effectiveness of treatment methods for lymphoceles. MATERIALS AND METHODS: During 2004 to 2010, we performed 242 kidney transplantations in 92 female and 150 male patients. The hemostatic parameters included concentrations of: antithrombin, plasminogen, thrombin/antithrombin complexes (TAT), prothrombin products F1+2 (F1+2), d-dimers, and plasmin/antiplasmin complexes. RESULTS: At 7 years follow-up 27 (11%) recipients had developed symptomatic lymphoceles, namely abdominal discomfort, a palpable mess in the lower abdomen, arterial hypertension, infection of the operative site with fever, lymphorrhoea with surgical wound dehiscence, decreased diurnal urine output with an elevated plasma creatinine, voiding problems of urgency and vesical tenesmus, and/or symptoms of deep vein thrombosis. We applied the following methods of treatment aspiration alone, percutaneous drainage, laparoscopic fenestration or open surgery. In two only patients did perform open surgery. Since 2008 we have not performed an aspiration alone because of high rate of recurrence (almost 100%) and abandoned open surgery in favor of a laparoscopic approach. Our minimally invasive surgery includes percutaneous drainage guided by ultrasound and a laparoscopic procedure with 100% effectiveness. The examined hemostatic parameters revealed decreased concentrations of TAT complexes and F1+2 in subjects with lymphocele showing positive predictive values of 33% and 41% respectively. The negative predictive values for TAT complexes and F1+2 were 14% and 10%, respectively, suggesting decreased blood coagulation activity among effected recipients. Altered blood coagulation processes may explain some aspects of the disturbances of postoperative obliteration of damaged lymphatic vessels and formation of pathological lymph collection afterward. CONCLUSIONS: Perturbations of blood coagulation may be one cause for a lymphocele.

An age-related decrease in factor V Leiden frequency among Polish subjects.

Factor V Leiden (G1691A FV mutation) is a widely acknowledged risk factor of deep vein thrombosis, including pulmonary embolism as the most serious complication. However, its high prevalence of ~5%in the Caucasian population might be related to an unknown evolutionary advantage. It might exert a beneficial effect on the carrier, e.g. protecting women from excessive bleeding during labour or allowing increased survival in severe sepsis or with other inflammatory diseases. The aim of our study was to verify or contradict the hypothesis of a favourable association between the A allele (A1691) and longevity in the Polish population. For this purpose, the G1691A mutation was analyzed by PCR-RFLP in 1016 Poles: 400 neonates (187 female and 312 male), 184 healthy adults (129 female and 55 male), and 432 long-lived individuals (age ≥95 years: 343 women and 89 men). Frequencies of G1691A carriers and the A1691 allele in long-lived individuals (0.2% and 0.1%, respectively) were significantly lower than in neonates (4.2% and 2.2%, respectively) and adults (3.3% and 1.6%). The frequency of the G1691A factor V Leiden mutation decreased with age, which indicates a shorter survival time among A1691 allele carriers in the Polish population.