TNF Alpha−308 Genotype and Renin–Angiotensin System in Hemodialysis Patients: An Effect on Inflammatory Cytokine Levels?

BACKGROUND: Renin-angiotensin system (RAS) was suggested to modulate inflammatory cytokine production. Angiotensin II was consistently shown to increase production of tumor necrosis factor alpha (TNF-alpha). However, inflammatory cytokines and RAS were modulated by genetic polymorphisms such as TNF-alpha-308 G > A and angiotensin-converting enzyme (ACE) I/D gene polymorphisms. The aim of this study was to investigate the effects of ACE and TNF-alpha genotypes on inflammatory cytokines in hemodialysis (HD) patients. METHODS: ACE I/D and TNF-alpha-308 G > A genotypes, pre- and postdialysis plasma renin activity (PRA), serum ACE, interleukin-1 beta (IL-1beta), and TNF-alpha levels were determined in 22 HD patients. RESULTS: Predialysis serum ACE activity is correlated with TNF-alpha (r = 0.63; P = 0.01), and PRA was correlated with IL-1beta levels (r = 0.49; P = 0.02). Pre/postdialysis IL-1beta and TNF-alpha were similar in DD and II/ID ACE genotypes. Predialysis TNF-alpha and IL-1beta (32.4 +/- 5; 35.1 +/- 4.2 vs. 28.1 +/- 3.7; 26.5 +/- 6.2 pg/mL; P < 0.05) and postdialysis TNF-alpha levels (30.4 +/- 1.4 vs. 28.4 +/- 0.82 pg/mL; P < 0.05) were significantly higher in TNF1/2 than TNF1/1 patients. CONCLUSION: ACE and TNF-alpha-308 G > A (1/2) gene polymorphisms may contribute to modulation of proinflammatory cytokine production and hence chronic inflammation in HD patients.     

Oxidized low density lipoprotein (Ox-LDL) as a marker of atherosclerosis in hemodialysis (HD) patients

AIM: To characterize the relationship between oxidative stress and atherosclerosis in HD patients. METHODS: Seventy-five HD patients were entered into the study. Ox-LDL was measured as a probe for peroxidation and compared to clinical atherosclerotic parameters. Prospective studies were also performed to assess the effects of vitamin E-bonded membrane on oxidative stress. RESULTS: Elderly patients tended to show elevated Ox-LDL (alpha = 0.060+/-0.021 ng/microg LDL protein/year, r = 0.35, p < 0.05). Levels of Ox-LDL in the patients with positive history for atherosclerotic diseases (3.1+/-0.4 ng/microg LDL protein, n = 36) were higher than those with a negative history (1.6+/-0.2, n = 39, p < 0.01). Further-more, ankle/brachial pressure index was negatively correlated to Ox-LDL (alpha = -0.052+/-0.012/ng/microg LDL protein, r = 0.42, p < 0.01). Application of vitamin E-bonded membrane for 10 months (-38+/-11%, n = 14, p < 0.05), but not synthetic membrane, ameliorated Ox-LDL. CONCLUSIONS: Our results indicate that Ox-LDL is elevated in aged HD patients. In addition, the present data provide evidence that vitamin E-bonded dialyzers attenuate oxidative stress. Finally, our findings suggest that Ox-LDL correlates to the magnitude of peripheral arterial diseases in HD patients.     

Expression of telomerase activity in thymoma and thymiccarcinoma tissues; a clinicopathological study

BACKGROUND: Telomerase is a nucleoprotein complex that caps the physical termini of all eukaryotic chromosomes. It is suggested that telomerase play important roles in unlimited cell division acquisition of the malignant phenotype. We studied the relation of telomerase activity in thymoma and thymic carcinoma to the clinicopathological features of these lesions. METHODS: Tissue specimens were surgically resected from patients with thymoma and thymic carcinoma. Telomerase activity was evaluated according to a modified telomeric repeat amplification protocol (TRAP) assay. RESULTS: Telomerase activity was detected in all thymic epithelial tumors. The activity (mean +/- SD: unit/microgram.protein) in thymoma (n = 17) was significantly higher than that in thymic carcinoma (n = 7) [431.8 +/- 400.1 vs. 68.8 +/- 39.8: p < 0.01]. Telomerase activities in thymoma and thymic carcinoma were significantly higher than that in primary lung adenocarcinoma (33.5 +/- 39.2: n = 47), studied as control (p < 0.01). In patients with thymoma, telomerase activity did not correlate with tumor stage according to Masaoka classification (p = 0.776). In patients with thymic carcinoma, however, telomerase activity positively correlated with tumor stage (p = 0.02). In thymoma, telomerase activity positively correlated with the ratio of induced lymphocytes according to Rosai's classification (p = 0.045). CONCLUSION: In thymoma, telomerase activity reflects the presence of immature T-cell lymphocytes in tumor tissue rather than tumor stage or malignant phenotype. In thymic carcinoma, telomerase activity derived directly from cancer cells may relate to tumor stage.     

Detection of telomerase activity in bronchial lavage as an adjunct to cytological diagnosis in lung cancer.

OBJECTIVE: Definitive diagnosis of lung cancer with conventional methods may sometimes be difficult in clinical practice. Telomerase is a ribonucleoprotein DNA polymerase that maintains the telomeric region of chromosomes during successive rounds of cell division. Telomerase activity in body cavity fluids has been advocated to be a potential diagnostic marker for malignancy. We investigated the diagnostic value of telomerase activity in bronchial lavage samples of patients undergoing diagnosis of lung cancer. METHODS: A total of 29 bronchial lavage samples were collected from patients in whom the diagnosis was confirmed with cytological and/or histological examinations. Patients were classified as lung cancer patients (Group 1, n = 22) and patients with benign disease (Group 2, n = 7). Telomerase activity was determined with polymerase chain reaction-based TRAP (The telomeric repeat amplification protocol) assay. RESULTS: Cytological examination was diagnostic in 12 (54.5%) of 22 patients in Group 1, and in all seven patients of Group 2 (P = 0.063). Telomerase activity was positive in 16 (72.7%) of Group 1 patients, while it was positive in only 1 (14.3%) sample of a lung abscess in Group 2 (P = 0.011). The sensitivity rate of cytological examination when combined with telomerase activity (81.8%) was significantly greater than that of cytological examination alone (54.5%) (P = 0.031). The sensitivity and specificity of telomerase activity were 72.7 and 85.7%, respectively. Telomerase activity had a positive predictive value as 0.94 and negative predictive value as 0.50. Diagnostic accuracy of telomerase activity was 75.8%. CONCLUSION: Telomerase activity in bronchial lavage is a highly sensitive diagnostic biomarker for malignancy and a potential complementary diagnostic technique to cytological examination in the diagnosis of lung cancer.     

In vitro production of interleukin-1 receptor antagonist in chronic renal failure, CAPD and HD.

Dialysis-related symptoms are believed to be mediated, at least in part, by monocyte/macrophage-derived pro-inflammatory cytokines including interleukin-1 (IL-1) and tumor necrosis factor (TNF). Measuring the production of interleukin-1 receptor antagonist (IL-Ra), a naturally occurring inhibitor of IL-1, opens avenues to study the balance between these two cytokines in patients. We studied the cell content and production of IL-1 beta and IL-Ra by unstimulated and endotoxin- or IgG-stimulated peripheral blood mononuclear cells (PBMC) in undialyzed patients with chronic renal failure (CRF), patients on continuous ambulatory peritoneal dialysis (CAPD) and patients on chronic hemodialysis with reuse cuprophan membranes (HD), and compared them to healthy controls. IL-1 beta and IL-Ra were measured by specific radioimmunoassay. IL-1 beta was undetectable in freshly harvested PBMC from healthy controls, CRF, CAPD or HD. In contrast, the content of IL-Ra in HD patients (2828 +/- 466 pg/ml) was significantly higher than that in healthy controls (643 +/- 53 pg/ml, P < 0.01), CRF (1097 +/- 320 pg/ml, P < 0.01) or CAPD (1398 +/- 390 pg/ml, P < 0.05). In endotoxin-stimulated PBMC, IL-1 beta production by HD patients (9375 +/- 1687 pg/ml) was not significantly different from healthy controls (8429 +/- 1621 pg/ml). However, endotoxin-stimulated IL-Ra production by HD patients (32,350 +/- 8276 pg/ml) was greater than that from healthy controls (11,284 +/- 1250 pg/ml, P < 0.001), CRF (12,263 +/- 2680 pg/ml, P < 0.01) or CAPD patients (11,822 +/- 1797 pg/ml, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Telomerase activity as a predictive marker for recurrence of hepatocellular carcinoma after hepatectomy

BACKGROUND: Expression of telomerase activity and stabilization of telomeres are concomitant with attainment of immortality in tumor cells. Telomerase activity levels in hepatocellular carcinoma (HCC) may serve as a predictive marker for recurrence after surgery. METHODS: Telomerase activity levels in HCC were measured in 37 patients undergoing hepatectomy by the telomeric repeat amplification protocol. The clinicopathologic factors and telomerase activity were analyzed to identify factors that were important in affecting recurrence of HCC and recurrence-free survival. RESULTS: Telomerase activity was detected in 23 patients (62.2%), and was not significantly associated with seven other HCC-related factors. After a median follow-up of 34 months, 24 patients (64.9%) had recurrence of HCC. In univariate analyses, telomerase activity of more than 20 total product generated (TPG) and portal vein invasion were found to be significantly related to a shorter time to recurrence. Multivariate analysis demonstrated that telomerase activity (>20 TPG) was significantly related to an increased risk of recurrence (relative risk 2.36, 95% confidence interval 1.03 to 5.43, P = 0.04). CONCLUSIONS: Telomerase activity can be identified as an independent predictor for recurrence after resection of HCC.     

Increased plasma adrenomedullin levels in hemodialysis patients with sustained hypotension

BACKGROUND: Sustained hypotension in end-stage renal disease patients is characterized, despite an overactivation of the sympathetic and renin-angiotensin systems, by decreased vascular resistance and a blunted vascular response to pressor stimuli. An increased production of one or more vasodilator substances might play a role in the reduced vascular resistance and response to pressor stimuli in these patients. We evaluated the possible role of an increased production of nitric oxide and/or adrenomedullin (ADM) in the pathophysiology of chronic hypotension in hemodialysis (HD) patients. METHODS: Three groups of hypotensive (N = 9), normotensive (N = 10), and hypertensive (N = 9) HD patients were included in the study. Plasma renin activity (PRA) and plasma levels of catecholamines, ADM, nitrite/nitrate (an estimator of nitric oxide production), tumor necrosis factor (TNF), and interleukin-1beta (IL-1beta) were measured. Plasma volume and left ventricular ejection fraction (LVEF) were also evaluated. RESULTS: Plasma levels of nitrite/nitrate and ADM were elevated in HD patients with respect to the reference values in normal subjects. Plasma ADM levels, but not nitrite/nitrate levels, were higher in hypotensive (368.1 +/- 25.4 pg/mL) than normotensive (225 +/- 9.9 pg/mL) and hypertensive HD patients (278.2 +/- 15.5 pg/mL, P < 0.01). When considering hypotensive and normotensive patients together, the mean blood pressure inversely correlated with time on HD (r = -0. 53, P < 0.05) and plasma ADM levels (r = -0.78, P < 0.01). CONCLUSIONS: Plasma ADM and nitrite/nitrate levels are increased in HD patients, but only ADM levels were higher in hypotensive than in normotensive and hypertensive HD patients. The higher plasma levels of this peptide in hypotensive patients and its inverse correlation with mean arterial pressure suggest that ADM may be involved in the pathophysiology of chronic hypotension in HD patients.     

Telomerase activity in renal cell carcinoma by modified telomeric repeat amplification protocol assay

BACKGROUND: Previous assessments by the conventional telomeric repeat amplification protocol have not been reliable for the quantitation of telomerase activity. We, therefore, determined telomerase activity in renal cell carcinoma (RCC) tissue by the modified sensitive telomeric repeat amplification protocol assay. METHODS: Telomerase activity was examined in 23 cases of RCC and in the adjacent normal kidney tissue, and assessed for associations with clinical and pathological variables of the disease. RESULTS: The linearity and quantitation of the modified method was confirmed. Mean telomerase activity of RCC (1987.889 +/- 1232.801 units) was significantly greater than that of normal renal tissue (173.467 +/- 241.893 units) (P = 0.0001). Telomerase activity in RCC was, however, not associated with clinical or pathological variables such as clinical stage (P = 0.8941), grade (P = 0.8043) or pathological subtype (P = 0.9739). CONCLUSION: The results suggest that telomerase might play a crucial role in an initial step of the development of RCC, but not in the progression of the disease.     

Telomerase activity in periampullary tumors correlates with aggressive malignancy

OBJECTIVE: To determine the presence of telomerase activity in a variety of periampullary malignancies and pancreatic diseases and quantify its activity to establish any association with the stage or aggressiveness of malignancy. SUMMARY BACKGROUND DATA: Progressive shortening of telomeres, repetitive DNA sequences at the ends of chromosomes, plays a role in cell senescence. Telomerase catalyzes conservation of telomeric repeats and may promote cell immortality and hence malignancy. It is absent in normal tissues but upregulated in more than 80% of cancers. METHODS: Fresh specimens of 62 periampullary tumors were snap-frozen in liquid nitrogen and adjacent tissue was formalin-fixed for histopathology. The telomerase repeat amplification protocol (TRAP) was used to obtain telomerase DNA products. These were separated with gel electrophoresis, stained with SYBR green, and quantified by densitometry. Findings were confirmed with a fluorometric TRAP assay in which fluorescent primers specific for telomerase were selectively amplified in its presence. RESULTS: Telomerase activity was upregulated in 26 of 33 periampullary malignancies (79%): 17 of 21 pancreatic adenocarcinomas (81%), 2 of 2 cholangiocarcinomas, 2 of 2 duodenal carcinomas, and 5 of 8 ampullary carcinomas (63%). Poorly differentiated periampullary tumors had significantly higher telomerase activity than well-differentiated tumors, and tumors larger than 2 cm had significantly higher telomerase activity than those 2 cm or smaller. Pancreatic ductal adenocarcinomas with lymph node metastases had significantly greater activity than node-negative cancers. Two of 11 intraductal papillary mucinous tumors were positive for telomerase activity, but only in foci of invasive carcinoma. Chronic pancreatitis (n = 7), serous cystadenomas (n = 5), benign mucinous cystic neoplasms (n = 4), neuroendocrine cancer (n = 1), and acinar cell carcinoma (n = 1) had no detectable telomerase activity. CONCLUSION: Telomerase activity is common in periampullary carcinomas. The magnitude of activity correlates with aggressiveness in pancreatic adenocarcinoma and may prove useful as a molecular index for biologic staging.     

Prognostic impact of telomerase activity in non-small cell lung cancers

OBJECTIVE: To evaluate the clinical significance of telomerase activity, particularly in terms of prognostic impact, in non-small cell lung cancer (NSCLC). SUMMARY BACKGROUND DATA: Telomerase activity has been found in various tissues. The activation of telomerase is considered necessary for the immortalization of human tumor cells, including NSCLC. METHODS: The authors studied 103 NSCLC specimens using a polymerase chain reaction based on a telomeric repeat amplification protocol assay. RESULTS: Telomerase activity was detected in 85 (82.5%) of 103 NSCLC specimens but in none of the paired normal lung tissue specimens. More cases of positive telomerase activity were observed in the group with advanced disease and in the group with poorly differentiated tumors. Such factors as the mean age at surgery, sex, smoking, histologic type, and size of tumor extension did not correlate with the telomerase activity. The Kaplan-Meier survival curves in all patients with NSCLC demonstrated that patients with telomerase-positive tumors survived for a significantly shorter period than those with a telomerase-negative tumor (p = 0.0058). According to a multivariate analysis, telomerase activity was identified as an independent prognostic factor (RR = 8.62, p = 0.035). CONCLUSIONS: Telomerase activity was one of the most important prognostic factors in patients with NSCLC, and its potential prognostic implication was independent of tumor stage.     

Imbalance between production and scavenging of hydroxyl radicals in patients maintained on hemodialysis

Background Reactive oxygen species are as being related to the pathophysiology of endstage renal disease (ESRD). We measured the plasma hydroxyl radical (·OH)-producing ability and ·OH-scavenging activity in patients with ESRD to clarify the pathophysiological states involved. Methods We used electron spin resonance to measure plasma N-t-butyl-α-phenylnitron radical spin adduct (pPBN rsa) as ·OH-producing ability and plasma 3,3,5,5-tetramethyl-1-pyrroline-N-oxide radical spin adduct (pM4PO rsa) as ·OH-scavenging activity. Oxidative injuries were evaluated by determining oxidised low-density lipoprotein (Ox-LDL). Results The pPBN rsa of the ESRD patients was lower than that of the controls (1.83 vs 2.94 μmol/g protein). The pM4PO rsa of the ESRD patients was higher than that of the controls (3.85 vs 3.15 mmol l-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl hydrogen phosphate] potassium salt (EPC-K₁)/g protein). The pPBN rsa and pM4PO rsa were correlated, both in the ESRD patients and in the controls (r = 0.47 and r = 0.53). Ox-LDL was correlated with hemodialysis (HD) duration (r = 0.49) and was negatively correlated with pPBN rsa (r = −0.54), which indicates that oxidative stress was increased as HD therapy was prolonged and suppressed pPBN rsa. Conclusions There was an imbalance between ·OH-producing ability and ·OH-scavenging activity, in the ESRD patients, and this may be responsible for compromising the health of ESRD patients.     

Evaluation of hemodialysis adequacy using online Kt/V and single-pool variable-volume urea Kt/V

OBJECTIVE: The hemodialysis (HD) team should deliver single-pool variable-volume (SPVV) urea Kt/V>or=1.2. At present dialysis machines provide online assessment of Kt/V. The aim of our study is to assess if online Kt/V and SPVV urea Kt/V yield similar values and if it may be replaced in evaluation of HD adequacy. PATIENTS AND METHODS: Studies were carried out two times (evaluation I and evaluation II) in 40 patients dialyzed using machines with online Kt/V monitoring by the conductivity method. During the middle HD session in the week, SPVV Kt/V was estimated from urea measurements in serum at the beginning and at the end of the HD session using the second generation formula of Daugirdas. Values of SPVV urea Kt/V and simultaneously obtained online Kt/V were compared. RESULTS: In I, SPVV Kt/V was 1.37+/-0.16, and online Kt/V was 1.16+/-0.14 (P=0.000), r=0.559 (P=0.000); a regression equation indicated SPVV Kt/V as 0.62457+0.64048 * online Kt/V. In II, estimated SPVV Kt/V was 1.37+/-0.20, online Kt/V-1.16+/-0.15 (P=0.000), r=0.493 (P=0.001), and calculated SPVV Kt/V was 1.37+/-0.10. In I, SPVV urea Kt/V>1.20 was shown in 87.5% of patients, whereas online Kt/V>1.20 was observed in 37.5% of cases (P=0.000). In II, respective values were 82.5% and 40.0% of patients (P=0.000). CONCLUSIONS: SPVV urea Kt/V indicates a more adequate HD session than online Kt/V. This difference has to be considered when applying Kt/V to clinical practice.     

Cardiac troponin I and beta 2 microglobulin as risk factors for early-onset atherosclerosis in patients on haemodialysis

AIM: To investigate the associations of different risk factors with carotid artery intima-media thickness (C-IMT) in non-diabetic haemodialysis (HD) patients who had no clinical evidence of atherosclerosis. METHODS: Seventy-two HD patients (43 men, 29 women; mean age: 34.5 +/- 10.6 years; mean time on HD: 47.9 +/- 40.0 months) and 40 age- and sex-matched healthy controls (26 men, 14 women; mean age: 35.5 +/- 7.1 years) participated in the study. The relationship between C-IMT and haematocrit-corrected erythrocyte sedimentation rate (Hct-corrected ESR), beta 2 microglobulin (beta2M) and serum cardiac troponin I (cTnI) levels beyond C-reactive protein (CRP), lipid profile and lipoprotein(a), fibrinogen, homocysteine and left ventricular hypertrophy (LVH) were examined. RESULTS: Mean C-IMT of the HD patients was significantly greater than that of the control subjects (0.59 +/- 0.06 vs 0.53 +/- 0.07 mm, P = 0.002). C-IMT of patients was positively correlated with age (r = 0.33), body mass index (r = 0.40), Hct-corrected ESR (r = 0.37), CRP (r = 0.34), beta2M (r = 0.34), cTnI (r = 0.26), triglyceride (r = 0.26) and fibrinogen (r = 0.28) levels (P < 0.05 for all). The mean C-IMT was significantly greater in patients with LVH than it was in those without LVH (P = 0.004). In multivariate regression analysis, age (P = 0.02), beta2M (P = 0.001), log-transformed CRP (P = 0.03) and LVH (P = 0.01) were independently related with C-IMT. CONCLUSION: Besides well-known cardiovascular (CV) risk factors, cTnI and beta2M were related with C-IMT in that they may have important roles in early-onset atherosclerosis in this high-risk population.     

SYBR-14/PI双染法流式细胞术检测精子质膜完整性的研究

目的:探讨应用荧光染料SYBR-14/碘化丙啶(SYBR-14/PI)双色标记法进行流式细胞术检测精子质膜完整性的可行性及其临床意义。方法:收集208例男性精液标本,按WHO精液分析标准分为正常组(n=31)与异常组(n=177)。通过计算机辅助精液分析系统进行精液常规分析。精液标本洗涤处理后经SYBR-14/PI双染后上流式细胞仪(FCM)分析,用发绿色荧光精子百分率(SYBR-14+/PI-%)表示质膜完整精子(PMI)的比例。结果:正常组与异常组SYBR-14+/PI-与SYBR-14-/PI+精子百分率均存在统计学差异(P均<0.05)。正常组精子SYBR-14+/PI-%为(55.66±20.64)%,显著高于异常组[(39.71±19.21)%,P=0.000]。208例标本中,SYBR-14+/PI-%与精子活动率呈显著正相关(r=0.408,P=0.000),与(a+b)级精子百分率呈显著正相关(r=0.398,P=0.000),与d级精子百分率呈显著负相关(r=-0.413,P=0.000);SYBR-14-/PI+%与精子活动率呈显著负相关(r=-0.380,P=0.000),与(a+b)级精子百分率呈显著负相关(r=-0.397,P=0.000),与d级精子百分率呈显著正相关(r=0.385,P=0.000);SYBR-14+/PI+%与精子活动率呈正相关(r=0.172,P=0.013),与(a+b)级精子百分率呈正相关(r=0.177,P=0.011),与d级精子百分率呈负相关(r=-0.164,P=0.018)。结论:应用流式细胞术SYBR-14/PI双染法检测精子质膜完整性具有可行性,可用于评估男性生育力。     

Long-term use of vitamin E-coated polysulfone membrane reduces oxidative stress markers in haemodialysis patients.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and an independent predictor of overall mortality and cardiovascular outcome in haemodialysis (HD) patients. In the present study, we compared the effects of a vitamin E-coated polysulfone membrane (PSE) and a non-vitamin E-coated polysulfone membrane (PS) on oxidative stress markers such as ADMA. METHODS: Thirty-one HD patients were enrolled to this investigation. They were allocated into two groups: in the PSE group (n = 16), PSE was used for 6 months, followed by PS for an additional 12 months; in the PS group (n = 15), PS was used for the entire observation period. Plasma ADMA, oxidized low density lipoprotein (Ox-LDL) and malondialdehyde LDL (MDA-LDL) levels were measured at baseline, 3, 6, 12 and 18 months. Plasma ADMA in peritoneal dialysis (PD) patients and in healthy individuals was also measured. RESULTS: Predialysis concentrations of ADMA (0.72+/- 0.13 nmol/ml) were significantly higher in the HD group than in both PD patients (0.63+/-0.10 nmol/ml, P<0.01) and healthy individuals (0.44+/-0.01 nmol/ml, P<0.0001). Treatment with PSE for 6 months significantly reduced predialysis levels of ADMA (0.54+/-0.09 nmol/ml) compared with baseline (0.74+/-0.12 nmol/ml; P<0.01). Predialysis levels of Ox-LDL and MDA-LDL after 6 months therapy with PSE were also significantly lower than baseline values. Treatment with PS subsequent to treatment with PSE again increased ADMA, Ox-LDL and MDA-LDL back to baseline levels. In the PS group, ADMA, Ox-LDL and MDA-LDL levels remained unchanged during the entire treatment period of 18 months. CONCLUSIONS: We confirmed that use of PSE reduced ADMA that had accumulated in HD patients. This finding indicates that PSE exerts anti-oxidant activity. A randomized controlled study will be required to determine whether PSE prevents cardiovascular diseases and other dialysis-related complications by reducing oxidative stress.     

Effect of renal dialysis therapy modality on T cell cytokine production.

INTRODUCTION: Dialysis has been associated with acute changes in the complement activation status, granulocyte markers, macrophage function, T cell activation and the release of pro-inflammatory cytokines. The most common analysis of cytokine production in patients on dialysis has focused on the changes in monokines (particularly IL-1 and TNF alpha), however it is becoming clear that T cell cytokines play a major role in the impaired lymphocyte function of dialysis patients. METHODS: To assess the effect of dialysis modality on T cell function we analysed the ability of T cells within peripheral blood mononuclear cell populations (PBMC) to produce cytokines after mitogen (phorbol-12-myristate-13-acetate; PMA and lonomycin; I) stimulation in patients on peritoneal dialysis (PD) compared to low flux haemodialysis (HD) and normal individuals (controls). RESULTS: In control PBMC, PMA + I stimulation significantly increased the percentage of CD3+ cells expressing IL-2, IFN gamma, TNF alpha, IL-4 and IL-10, as expected. However, although mitogen stimulation significantly enhanced the percentage of the classical Th1 cytokines (IL-2, IFN gamma and TNF alpha) in the low flux HD PBMC, it had no effect on CD3+ IL-2 or CD3+ TNF alpha producing cells in the PD group. In contrast, the percentage of T cells producing Th2 cytokines (IL-4 and IL-10) could not be consistently enhanced by mitogen in either dialysis group. CONCLUSIONS: We suggest that PD alters the ability of T cells to produce cytokines, possibly by causing an 'exhaustion' of the Th1 cells, thereby preventing cells to produce cytokine on ex vivo stimulation. Furthermore, since T cells from both low flux HD and PD groups could not be induced to produce Th2 cytokines we suggest that uraemia or dialysis per se inhibits T cells from producing Th2 cytokines.