Comparing efficacy and safety of P013, a proposed pertuzumab biosimilar, with the reference product in HER2-positive breast cancer patients: a randomized, phase III, equivalency clinical trial.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the leading reason for cancer-related death among women. Neoadjuvant treatment with dual-HER2 (human epidermal growth factor receptor 2) blockade has shown promising effects in this regard. The present study aimed to compare the efficacy and safety of a proposed pertuzumab biosimilar with the reference pertuzumab. METHODS: This randomized, phase III, multicenter, equivalency clinical trial was conducted on chemotherapy-naive women with HER2-positive breast cancer. Patients were randomly assigned (1:1) to receive six cycles of either P013 (CinnaGen, Iran) or the originator product (Perjeta, Roche, Switzerland) along with trastuzumab, carboplatin, and docetaxel every 3 weeks. Patients were stratified by cancer type (operable, locally advanced, inflammatory) and hormone receptor status. The primary endpoint was breast pathologic complete response (bpCR). Secondary endpoints included comparisons of total pCR, overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. RESULTS: Two hundred fourteen patients were randomized to treatment groups. bpCR rate in the per-protocol population was 67.62% in the P013 and 71.57% in the reference drug groups. Based on bpCR, P013 was equivalent to the reference pertuzumab with a mean difference of - 0.04 (95% CI: - 0.16, 0.09). Secondary endpoints were also comparable between the two groups. CONCLUSIONS: The proposed biosimilar P013 was equivalent to the reference product in terms of efficacy. The safety of both medications was also comparable.

Evaluating the safety and effectiveness of PegaGen® (pegfilgrastim) for the prevention of chemotherapy-induced febrile neutropenia: a post-marketing surveillance study.

PURPOSE: Phase IV clinical trials are required to evaluate the real-world safety and effectiveness of drugs. This study aimed to evaluate the safety and effectiveness of once-per-cycle administration of PegaGen® (pegfilgrastim, CinnaGen, Iran) in cancer patients. METHODS: In this open-label, multicenter, prospective, real-world, post-marketing surveillance study, patients with any type of cancer receiving chemotherapy regimens with a high risk of febrile neutropenia (FN) were included if they were prescribed pegfilgrastim for FN prophylaxis. The primary objective of this study was to assess the safety and the secondary objective was to assess the effectiveness of pegfilgrastim in the prevention of FN in cancer patients. RESULTS: A total of 654 patients (51.73 ± 15.12 years of age) were enrolled and 3615 cycles of pegfilgrastim injections were recorded. The most common malignancies among the study patients were breast cancer (n = 192, 29.36%), lymphoma (n = 131, 20.03%), and gastric cancer (n = 65, 9.94%). The median (Q1, Q3) number of pegfilgrastim cycles per patient was 6 (4, 7). A single 6 mg dose was injected in 99.17% of the cycles. A total number of 816 adverse events (AEs) were reported in 246 patients (37.62%). Bone pain was recorded in 141 patients (21.56%) and in 440 cycles (12.17%). Among all patients, 45 patients (6.88%) experienced FN 51 times, and FN frequency was 1.4% among cycles. Moreover, 14 (2.14%) patients were hospitalized following FN. Antibiotics were administered to 24 patients (3.67%) for FN treatment. CONCLUSION: The results from this post-marketing surveillance study support the safety and effectiveness of PegaGen® used for the prevention of chemotherapy-induced FN in patients with various types of cancer and treatment regimens. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04460079.

CD markers variations in chronic lymphocytic leukemia: New insights into prognosis.

Chronic lymphocytic leukemia (CLL) is one of the most commonly occurring adult leukemias that is associated with clonal accumulation of mature apoptosis-resistant B-cells in bone marrow, peripheral blood, and specific tissues. Different pathogenesis factors can contribute to the aggression of the clinical course in this disease. Cytogenetic abnormalities and surface biomarkers of neoplastic CLL cells can be effective in the outcome of CLL, and the examination of changing CD markers expressions in the progression of CLL can be related to the prognosis of this disease. Changing expression levels of CD markers on lymphocytes and other cells in CLL patients can play a role in the aggressive clinical outcomes such as organomegaly, immunodeficiency, and advanced disease stages through their interaction with CLL microenvironment. Given the involvement of CD markers in the pathogenesis of CLL, it can be stated that recognizing the expression changes of CD markers in the cells involved in CLL can be a proper approach to evaluate prognosis among these patients.

Evaluation of HLA-B*05, *07, *08, *27 and *51 Allele Expression in Adults with Immune Thrombocytopenic Purpura.

Background: Immune thrombocytopenic purpura (ITP) is an immune mediated acquired disease characterized by isolated thrombocytopenia. Since there is no specific and sensitive biomarkers to guide treatment of ITP patients, this study aimed to evaluate the possible application of human leukocyte alleles HLA-B5, 7, 8, 27 and 51 and their association with patients' laboratory data and clinical findings. Methods:Thirty-one adult patients with chronic ITP were included in the present study. Human leukocyte antigen (HLA) typing was done using the standard lymphocytotoxicity HLA typing method. Moreover, patients' medical records were used to collect data about disease presentations, platelet count at diagnosis. Results:Our study included 31 patients (25 females and six males) with a mean age of 40.23±17.06 years. Among all participants, HLA-B5 (25.8%) and HLA-B51 (22.6%) alleles were the most prevalent alleles, followed by HLA-B7 (9.7%) and HLA-B8 (9.7%), HLA-B27 (3.2%). The mean platelet count significantly was lower in patients with HLA-B5 (16.13x10³/µL versus 36.63x10³/µL) (P=0.01) and HLA-B51 (14.14x10³/µL versus 36.24x10³/µL) (P=0.04). Also, epistaxis and gingival bleeding were observed in patients with 11.5x10³/µL mean platelet count (P=0.04). In addition, lymphocyte and neutrophil cell counts were significantly associated with the expression of HLA-B*05 and HLA-B*51 antigens (P <0.05). Conclusions:According to the present study results, it seems that HLA-B5 and HLA-B51 alongside complete blood count test parameters may have a positive relationship in ITP patients.

The role of melatonin on caspase-3-like activity and expression of the genes involved in programmed cell death (PCD) induced by in vitro salt stress in alfalfa (Medicago sativa L.) roots.

BACKGROUND: Alfalfa (Medicago sativa L.) is the most cultivated forage plant as a model in legumes. Salinity stress due to Na+ toxicity causes severe, oxidative stress as a main reason for program cell death (PCD) in plants. Melatonin application can increase plant productivity in response to diverse stressors via modulating plant antioxidant mechanisms and PCD inhibition in plants. RESULTS: Alfalfa roots were subjected to different concentrations of in vitro salinity supplemented with melatonin (0.1, 10 and 15 µM) for ten days. Application of melatonin under salinity stress reduced ROS, H2O2 and [Formula: see text] content and showed a dramatic impact on TTC reduction and augmented cell viability. Interestingly, melatonin inhibited caspase 3-like protease activity and could decrease DNA fragmentation induced by salinity while increased expression of anti-apoptotic genes BI-1, UCP1-UCP2 involved in PCD pathway. In contrast, in 300 mM salinity, γVPE gene as a proapoptotic of PCD down-regulated significantly. CONCLUSIONS: For the first time, present data showed that, melatonin plays a major function in preventing PCD in alfalfa root meristem cells. We attempted to offer a mechanism for the function of melatonin as an anti-apoptotic agent by demonstrating significant actions of melatonin on mitochondria proteins, such as UCPs, in a manner similar to animal cells.

Proteome analysis of soybean leaves, hypocotyls and roots under salt stress.

BACKGROUND: Salinity is one of the most widespread agricultural problems in arid and semi-arid regions that makes fields unproductive, and soil salinization is a serious problem in the entire world. To determine the effects of salt stress on soybean seedlings, a proteomic technique was used. RESULTS: Soybean plants were exposed to 0, 20, 40, or 80 mM NaCl for one week. The effect of treatment at 20 mM NaCl on plant growth was not severe, at 80 mM NaCl was lethal, and at 40 mM NaCl was significant but not lethal. Based on these results, proteins were extracted from the leaves, hypocotyls and roots of soybean treated with 40 mM NaCl. Nineteen, 22 and 14 proteins out of 340, 330 and 235 proteins in the leaves, hypocotyls and roots, respectively, were up- and down-regulated by NaCl treatment. In leaves, hypocotyls and roots, metabolism related proteins were mainly down-regulated with NaCl treatment. Glyceraldehyde-3-phosphate dehydrogenase was down-regulated in the leaf/hypocotyls, and fructokinase 2 was down-regulated in the hypocotyls/root with NaCl treatment. Stem 31 kDa glycoprotein precursor was up-regulated in all three organs with NaCl treatment. Glyceraldehyde-3-phosphate dehydrogenase was specifically down-regulated at the RNA and protein levels by salt stress. CONCLUSION: These results suggest that metabolism related proteins play a role in each organ in the adaptation to saline conditions.

Rosmarinic acid inhibits programmed cell death in Solanum tuberosum L. calli under high salinity.

Oxidative stress induced by salinity is a prime cause of cell death when Na+ toxicity becomes unbearable. We explored the effect of rosmarinic acid (RA) on the Solanum tuberosum L. cv. Desiree calli against salt-induced programmed cell death (PCD). We showed that PCD events were triggered in calli under 250 mM NaCl by the loss of plasma membrane integrity as measured by the amount of malondialdehyde (MDA) in the cytoplasm, the degree of DNA degradation resulting from the cleavage of nuclear DNA into oligonucleosomal fragments in apoptotic cells, the presence of TUNEL-positive nuclei (90 ± 0.005%) damage in genomic DNA, and activation of caspase 3-like protease. Callus Formation Medium (CFM) supplemented with RA led to the suppression of salt-induced cell death and a dramatic decrease in the MDA level and frequency of TUNEL-positive nuclei under salinity to 4 ± and 7.3 ± % in the presence of 50 and 350 µM RA, respectively. The application of RA also resulted in an increase in GSH content and maintenance of a high GSH/GSSG ratio. Interestingly, these reductions in PCD were accompanied by inhibiting caspase 3-like protease activities due to RA under salinity. Molecular docking predicted high binding energies of RA for binding to subtilisin-like protease (StSCTc-3), which has caspase-3 like activity in Solanum tuberosum, near the active site. This finding supports the notion of a role for RA in PCD protection in plants, which is consistent with earlier reports in animal cells.

Potato responds to salt stress by increased activity of antioxidant enzymes.

To understand the response of potato to salt stress, antioxidant enzyme activities and ion content were analyzed for a sensitive and a tolerant cultivar. Nodal cuttings of the tolerant cultivar, Kennebec, and the sensitive cultivar, Concord, were exposed to media without or with 30, 60, 90 or 120 mmol/L NaCl for 4 weeks. On exposure to NaCl, the length and fresh and dry weight of both shoots and roots of Concord showed greater decrease than those of Kennebec. The decrease in shoot growth was more severe than that of the root for both cultivars. The K(+) content of shoots and roots of both cultivars was reduced in a dose-dependent manner by exposure to NaCl; the Na(+) content increased. Activities of ascorbate peroxidase, catalase and glutathione reductase were increased in NaCl-exposed shoots of Kennebec; the corresponding activities in NaCl-exposed shoots of Concord were decreased. Roots of both cultivars showed similar changes in the activities of these enzymes on exposure to NaCl. These studies established that enzyme activities in Concord shoots are inversely related to the NaCl concentration, whereas those in Kennebec do not show a dose dependency, which is also the case for the roots of both cultivars. Our findings suggest that an increase in activity of antioxidant enzymes, such as ascorbate peroxidase, catalase and glutathione reductase, can contribute to salt tolerance in Kennebec, a salt resistant cultivar of potato.

Sesquiterpene lactones from shoot culture of Artemisia aucheri with cytotoxicity against prostate and breast cancer cells.

Plant tissue culture is used to grow plant cells, tissues, or organs under sterile and determined conditions on culture media. It is alternative to traditional vegetative propagation, and is applied as an effective technology for the production of valuable secondary metabolites. The Artemisia aucheri (A. aucheri) was obtained from shoot culture grown on MS (Murashige and Skoog 1962) medium. Shade-dried aerial parts of in vitro grown A. aucheri (50 g) were extracted with dichloromethane-acetone (90:10). The extract was submitted for isolation to sephadex gel chromatography and preparative thin layer chromatography, which resulted in identification of one known eudesmanolide named artemin or 2,5-dihydroxy-12, 6-eudesmanolide-4(15)-en for the first time in this plant. In cell cytotoxicity test, artemin showed cytotoxic activity against DU-145,LNCaP prostate cancer, and MCF-7 breast cancer cells with IC50 values of 82.2 ± 5.6, 89.1 ± 6.3 and 111.5 ± 6.7 µM , respectively. Artemin was more active against prostate cancer cells with approximately same cytotoxicity against LNCaP androstane dependent cells and DU 145 which is androstane independent.

The Expression of Microvesicles in Leukemia: Prognostic Approaches.

Microvesicles (MVs) are the smallest subclass of the extracellular vesicles (EVs) spontaneously secreted by the external budding from the cell membranes in physiologic and pathologic conditions. The MVs derived from leukemic cells (LCs) can be detected by the expression of specific cluster of differentiation (CD) markers indicating their cellular origin while they can transfer different agents such as microRNAs, cytokines, and chemokines. The secretion of these agents from MVs can affect the vital processes of LCs such as cell cycle, proliferation, differentiation, and apoptosis. According to the effects of MVs components on the vital processes of LCs, it has been postulated that a change in the expression of MVs might be involved in the progression and prognosis of leukemia. However, further studies are needed to confirm the association between the presence of MVs and their components with the prognosis of leukemia. It seems that the identification of the prognostic values and the application of them for the detection of MVs in leukemia can provide new therapeutic targets for monitoring the status of patients with leukemia.

Human leukocyte antigens in cancer metastasis: Prognostic approach and therapeutic susceptibility.

Human leukocyte antigens (HLA), which are a group of antigen-presenting proteins, are classified into two main groups: classic (including HLA-I, HLA-II, HLA-III) and non-classic. These molecules are expressed on the surface of several immune cells, which contribute to the defense of body against foreign antigens. Changing expressions of these molecules on tumor cells can be related to reduced ability of the immune system in killing tumor cells, as well as metastasis induction of many solid tumors. The purpose of this review article is to assess the possible relationship between changing expressions of HLA molecules with cancer metastasis and relapse. It can be stated that the changes in the expressions of HLA molecules on tumor cells are an important mechanism for tumor cell escape from immune cells. Therefore, these changes can be associated with tumor development, metastasis, or relapse. Given the essential role of HLA molecule expression in cancer metastasis and relapse, identification of prognostic value of these alterations as well as targeting HLA molecules with new therapeutic approaches may lead to the prevention of these complications.

Expression of CD markers in JAK2V617F positive myeloproliferative neoplasms: Prognostic significance.

Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders characterized by the presence of JAK2V617F mutation. Thrombohemorrhagic as well as autoimmune or inflammatory phenomena are common clinical outcomes of these disorders. Recent studies have shown that abnormality in frequency and function of blood cells manifested by an alteration in CD markers' expression patterns play a key role in these complications. So, there may be a relationship between CD markers' expressions and prognosis of JAK2V617F positive MPNs. Therefore, in this review, we have focused on these abnormalities from the perspective of changing expressions of CD markers and assessment of the relationship between these changes with prognosis of JAK2V617F positive MPNs. It can be stated that the abnormal expression of a large number of CD markers can be used as a prognostic biomarker for clinical outcomes including thrombohememorrhagic events, as well as autoimmune and leukemic transformation in JAK2V617F positive MPNs. Considering the possible role of CD markers' expressions in JAK2V617F MPNs prognosis, further studies are needed to confirm the relationship between the expression of CD markers with prognosis to be able to find an appropriate therapeutic approach via targeting CD markers.

An outbreak of chickenpox in adult renal transplant recipients.

Infection with the varicella-zoster virus, the etiologic agent of chickenpox and herpes zoster, is more serious in immunosuppressed renal transplant recipients than it is in the general population. Chickenpox is a rare infection in adult renal transplant recipients; however, it is significant owing to the severity of its clinical features and its associated high mortality rate. To date, there are no reported outbreaks of primary varicella-zoster virus infection in adult renal transplant recipients. Here, we report 3 patients with chickenpox who presented to our center between May 2006 and June 2006.

Physiological targets of salicylic acid on Artemisia aucheri BOISS as a medicinal and aromatic plant grown under in vitro drought stress.

BACKGROUND: Artemisia aucheri BOISS is a medicinal and aromatic plant, which is endemic to mountainous areas of Iran and surroundings. In this study, we investigated the alleviating effects of salicylic acid (SA) pretreatment (0.01 and 0.1 mM) on A. aucheri under in vitro drought stress induced by 2 and 4% polyethylene glycol (PEG/6000). RESULTS: Plants exposed to PEG stress showed higher levels of H2O2, MDA and electrolyte leakage compared with control. While SA pretreatment decreased these parameters under PEG stress significantly. The activity of CAT, POD, APX, SOD and GR positively changed with PEG and more induction in activity of antioxidant enzymes was observed in SA-pretreated plants under PEG stress. Furthermore, ASA, GSH and their redox ratios (ASC/DHA and GSH/GSSG) enhanced with SA pretreatments. Analysis of our data revealed that MDA, DHA and H2O2 were the best targets for SA under in vitro PEG treatment for A. aucheri plants. CONCLUSIONS: Salicylic acid as a signal molecule mitigated adverse effects of PEG-simulated drought stress on A. aucheri under in vitro condition by improving the activity of antioxidant enzymes. In addition, protective role of SA was also related to promotion of ascorbate-glutathione cycle.

Antioxidant response of Stevia rebaudiana B. to polyethylene glycol and paclobutrazol treatments under in vitro culture.

This investigation was carried out with the aim of determining the effect of paclobutrazol (PBZ) (0 and 2 mg l(-1)) and polyethylene glycol (PEG) (0, 2, 4 and 6 % w/v of PEG 6000) treatments on antioxidant system of Stevia rebaudiana Bertoni under in vitro condition. Analysis of data showed that PEG treatment significantly increased hydrogen peroxide (H2O2) and phenolic contents, while PBZ treatment limited the effect of PEG on them. Our data revealed that PEG treatment significantly increased total antioxidant capacity, catalase (CAT), ascorbate peroxidase (APX), polyphenol oxidase (PPO) and peroxidase (POD) activity, while it inversely decreased glutathione reductase (GR) activity. The superoxide dismutase (SOD) activity was not affected by PEG treatment. PBZ treatment induced significantly higher levels of CAT and GR activity and lower levels of SOD activity in PEG-treated plants. PBZ in combination with PEG resulted in no significant difference on APX activity with PEG treatment alone. PBZ treatment prevented the effect of PEG on the PPO activity. PEG (with or without PBZ) treatment increased the ascorbate pool, whereas total glutathione level was not affected by PEG. Our finding indicated that PBZ reduced the negative effect of PEG treatment by quenching H2O2 accumulation and increasing the CAT activity. Collectively, the antioxidant capacity of S. rebaudiana in PEG treatment condition was associated with active enzymatic and non-enzymatic defence systems which partly could be improved by the PBZ treatment. In addition, a higher accumulation of phenolic compounds leads to a more potent reactive oxygen species scavenging activity in S. rebaudiana.

Alterations in antibiotic susceptibility of urinary tract infection pathogens.

BACKGROUND: Urinary tract infection (UTI) is the third most common infection in human. New resisted strains of uropathogens have been developed due to different factors such as widespread use of antibiothics. OBJECTIVES: We conducted this study to assess the recent pattern and susceptibility of uropathogens. MATERIALS AND METHODS: This descriptive cross-sectional study was carried on 32600 ambulatory patients' urine samples from six laboratories from 2008 to 2010 in Ahvaz, Khuzestan. Of those, 3000 positive culture were found. Data including underlying disease, pregnancy, catheterization and drug history were gathered by questionnaire. Susceptibility of pathogens to eight antimicrobial agents was determined. MATERIALS AND METHODS: This descriptive cross-sectional study was carried on 32600 ambulatory patients' urine samples from six laboratories from 2008 to 2010 in Ahvaz, Khuzestan. Of those, 3000 positive culture were found. Data including underlying disease, pregnancy, catheterization and drug history were gathered by questionnaire. Susceptibility of pathogens to eight antimicrobial agents was determined. RESULTS: Mean age of patients was 33.87 ± 3.80 years and 84.9% of them were female. The results showed that, E. coli, Kelebsiella and Enterobacter were the most common pathogens (73.5%, 13.8% and 6.6%, respectively). E. coli was susceptible to Ciprofloxacin, Amikacin, and Nitrofurantoin in 76.9%, 76.4% and 76.1% of cases, respectively. Klebsiella was more susceptible to Ciprofloxacin, Ceftizoxim and Amikacin in 81.1%, 79.9% and 87.7% of positive cultures. Enterobacter was most susceptible to Ciprofloxacin (71.7%), but completely resistant to Ampicillin unexpectedly. CONCLUSIONS: E. coli and other isolates were more sensitive to Gentamicin, Amikacin and Ciprofloxacin compared to the other antibiotics tested and therefore these may be the drugs of choice for the empiric treatment of community-acquired UTI in our region.

Alteration of panel-reactive antibodies following treatment with either atorvastatin or low-dose mycophenolate mofetil in sensitized hemodialysis patients.

INTRODUCTION: Both atorvastatin and mycophenolate mofetil (MMF) have been used for panel reactive antibodies (PRA) reduction in transplant candidates. The purpose of this study was to compare the effect of low-dose MMF and atorvastatin on PRA in sensitized hemodialysis patients waiting for kidney transplantation. MATERIALS AND METHODS: A total of 40 adult patients with end-stage renal disease who were highly sensitized to human leukocyte antigens (PRA > 40%) were enrolled and randomly assigned into atorvastatin or low-dose MMF groups. All of the patients received the treatments for 2 months. The PRA status was determined at the end of the 1st and 2nd month. RESULTS: Forty percent of the patients in the atorvastatin group compared with 5% in the low-dose MMF group showed complete response, defined as a minimum 50% reduction in PRA (P = .02). Reduction of PRA in the atorvastatin group was significantly higher than that in the low-dose MMF group (P = .01). No major infectious or other complications occurred in our patients. CONCLUSIONS: Atorvastatin has a significant effect on lowering of PRA in sensitized hemodialysis patients waiting for kidney transplantation. In addition, a short course of low-dose MMF is safe in ESRD patients; however, it has no effect on reduction of PRA.

Hypertension and microalbuminuria 5 years after pregnancies complicated by pre-eclampsia.

INTRODUCTION: Pre-eclampsia is part of a spectrum of conditions known as the hypertensive disorders of pregnancy. It is claimed that pregnant women with pre-eclampsia or eclampsia are at increased risk of kidney disease and hypertension later in life. We investigated whether Iranian women with a history of pre-eclampsia had higher rates of hypertension and microalbuminuria compared with women with uneventful pregnancy. MATERIALS AND METHODS: Medical records of pregnancies delivered at two hospitals in Ahvaz, between March 2001 and February 2003 were reviewed. Thirty-five pre-eclamptic women were identified and contacted for assessment of hypertension and albuminuria. They were compared with 35 women matched for year of delivery and age who had a pregnancy uncomplicated by hypertension. RESULTS: The mean follow-up from the index pregnancy was 5.7 years (range, 5.2 to 7.3 years). While only 1 woman (2.9%) in the control group was currently hypertensive, 28.6% of those with a history of pre-eclampsia (n = 10) were hypertensive (P = .003; relative risk, 10.0; 95% confidence interval, 1.35 to 74.00), 7 of whom were receiving antihypertensive medication at the time of evaluation. Among the formerly pre-eclamptic women, 7 had albuminuria (20.0%), whereas none of the controls were albuminuric (P < .001). Microalbuminuria was present in all hypertensive women in the pre-eclampsia group, but not in the only women in the control group with hypertension. CONCLUSIONS: We showed that in patients with a history of pre-eclampsia, there are increased risks of hypertension and microalbuminuria in the long term after pregnancy.

Changes in plasma concentrations of hypoxanthine and uric acid before and after hemodialysis.

INTRODUCTION: Purine metabolites constitute a major class of uremic toxins, and reliable characterization of which helps nephrologists to choose the most appropriate treatment for the patients individually. In the present study, we assessed plasma concentrations of hypoxanthine and uric acid as purine metabolites in patients on maintenance hemodialysis, before and after a dialysis session. MATERIALS AND METHODS: A total of 20 patients on maintenance hemodialysis were enrolled in this study. All of the patients underwent a routine 4-hour dialysis, as scheduled 3 times per week. Polysulfone membranes and bicarbonate dialysis solution were used in all dialysis sessions. Blood specimens were taken from the arteriovenous fistula immediately before and after one hemodialysis session, in order to measure plasma concentrations of hypoxanthine and uric acid by high-performance liquid chromatography, and to compare the predialysis and postdialysis values. RESULTS: Before hemodialysis, the mean plasma hypoxanthine and uric acid concentrations were 18.93 +/- 8.28 micromol/L and 44.16 +/- 22.88 micromol/L, respectively. After hemodialysis, these concentrations reduced to 13.68 +/- 4.42 micromol/L and 15.61 +/- 11.12 micromol/L, respectively. Hypoxanthine concentration had a 27.7% decrease after hemodialysis (mean difference, 5.25 +/- 6.24 micromol/L; 95% confidence interval, 2.32 to 8.10; P < .001). Also, uric acid concentration decreased by 64.6% (mean difference, 28.55 +/- 14.39 micromol/L; 95% confidence interval, 21.81 to 32.28; P < .001). CONCLUSIONS: Plasma concentrations of hypoxanthine and uric acid are higher than normal before hemodialysis, and they decrease significantly after hemodialysis; however, both of them may be still higher than normal values.