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Background The nucleotides and nucleosides of adenine are signaling molecules related to thromboregulation and modulation of immune responses in patients with malignancies. Thus, this study aims to determine NTPDase, 5′-nucleotidase, ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) activities in the platelets of patients with lung cancer. Methods We collected blood samples from patients ( n = 33) previously treated for lung cancer with chemotherapy. Patients were classified as stage IIIb and IV according to the Union for International Cancer Control (UICC). Results Patients showed a significant decrease in the hydrolysis of adenosine diphosphate (ADP) and adenosine, whereas the adenosine monophosphate (AMP) hydrolysis and platelet aggregation were significantly increased in this group. Adenosine triphosphate (ATP) hydrolysis did not show significant results between the group of patients and the control group. Conclusions We may suggest that ectonucleotidases as well as ADA are enzymes involved in thromboembolic events but especially here we may see that they are also directly involved in the generation of adenosine formation in the cancer patient circulation.

Background Uterine cervical neoplasia is an important worldwide malignancy sometimes associated with thrombosis. Ectonucleotidases are membrane-bound enzymes which participate in thromboregulation by hydrolyzing adenine nucleotides in the extracellular medium. In this sense, we aimed to investigate their activity in patients with uterine cervical neoplasia. Methods We evaluated NTPDase and 5′-nucleotidase activities from patients previously treated for uterine cervical neoplasia with either conization or radiotherapy (RTX). These patients were divided into four groups: two conization groups (I and II) and two RTX groups (III and IV), which were further divided based on the amount of time that had passed since the conclusion of their treatment, where groups I and III were extended-remission-period groups (patients with 1 to 5 years elapsed after the conclusion of treatment), and groups II and IV were recently treated patients (treated up to three months before). Results For both conization and RTX groups, ATP and ADP hydrolysis decreased in the extended-remission groups when compared to the control and recently treated groups. On the other hand, AMP hydrolysis was decreased in all the treated groups (both conization and RTX) compared to the control. CD39 expression was decreased in extended-remission groups (I and III) when compared to the other groups. Conclusions NTPDase protects against platelet aggregation and 5‘-nucleotidase is more involved in the control of adenosine formation.

NTPDase and 5'-nucleotidase activities in synaptosomes and platelets and oxidative stress parameters, such as TBARS levels, non-protein thiols and catalase activity were analyzed in rats submitted to demyelination by ethidium bromide (EB) and treated with vitamin E. The following groups were studied: I control (saline); II (canola oil); III (vitamin E); IV (EB) and V (EB and vitamin E). 2mg/kg of vitamin E were injected intraperitoneally in animals from groups III and V for seven days. After this time, the animals were submitted to euthanasia and samples were collected for biochemical assays. The results showed that NTPDase and 5'-nucleotidase activities were significantly increased in synaptosomes and platelets of rats from group IV when compared with the groups I, II, III and V (p

Ischemic stroke is a leading cause of mortality and disability particularly in the elderly. Hypertension is the most important risk factor in strokes, representing roughly 70% of all cases. Oxidative stress is believed to be one of the mechanisms taking part in neuronal damage in stroke. It is well documented that cholinergic system plays a key role in normal brain functions and in memory disturbances of several pathological processes, such as in cerebral blood flow regulation. This study investigated the oxidative status and acetylcholinesterase (AChE) activity in whole blood in patients diagnosed with acute and chronic stages of ischemia, as well as with hypertension. Malondialdehyde (MDA) levels and protein carbonylation content showed increased levels both in the acute ischemic groups and in the hypertensive group, when compared to the control. Catalase activity and reduced glutathione (GSH) levels in the acute group were also higher than in the hypertensive, chronic ischemic and control groups (p < 0.05). The activity of AChE in acute ischemic patients was significantly higher than that presented by the control, hypertensive and chronic ischemic patients (p < 0.05). The hypertensive group presented AChE activity significantly lower than control and chronic groups. In spite of having a defined location the ischemic event results in a systemic disorder that induces changes, which can be detected by measuring the peripheral markers of oxidative stress and AChE activity in erytrocytes.

Objectives To evaluate the oxidative status and antioxidant defense in patients with acute lymphoblastic leukemia (ALL). Design and methods We measured concentrations of plasmatic thiobarbituric acid reactive substances (TBARS), serum protein carbonylation, whole blood catalase (CAT) and superoxide dismutase (SOD) activities, as well as the plasmatic and erythrocyte thiol levels and serum vitamin E concentration. This study was performed on 80 children with ALL divided into 4 groups: just diagnosed, remission induction, remission maintenance and out-of-treatment. Results TBARS levels and serum protein carbonylation were higher in ALL patients than in controls and reduced levels of antioxidants were found in these patients. Conclusion These findings may indicate a possible link between decreased antioxidants and increased levels of cells alterations due to oxidative damage, supporting the idea that there is a persistence of oxidative stress in acute lymphoblastic leukemia.

The relation between adenine nucleotides and cancer has already been described in literature. Considering that the enzymes ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) act together to control nucleotide levels, we aimed to investigate the role of these enzymes in prostate cancer (PCa). E-NPP and ADA activities were determined in serum and platelets of PCa patients and controls. We also verified the influence of the Gleason score, bone metastasis and treatment in the enzyme activities. Platelets and serum E-NPP activity increased, whereas ADA activity in serum decreased in PCa patients. In addition, Gleason score, metastasis and treatment influenced E-NPP and ADA activities. We may propose that E-NPP and ADA are involved in the development of PCa. Moreover, E-NPP and ADA activities are modified in PCa patients with distinct Gleason score, with bone metastasis, as well as in patients under treatment.

Introduction Cervical cancer remains the second leading cause of death among women. Intraepithelial neoplasias and uterine invasive cancer are frequently associated with disturbances in coagulation and changes in the concentrations of adenine nucleotides. This work intended to analyze changes in extracellular adenine nucleotide hydrolysis and blood platelet aggregation in patients diagnosed for cervical intraepithelial neoplasia in different stages as well as uterine invasive cancer. Patients and methods NTPDase, E-NPP, 5′-nucleotidase, total ADA and its isoforms (ADA1 and ADA2), as well as the platelet aggregation from patients with different stages of cervical intraepithelial neoplasia (NICs I, NIC II, NIC III) and uterine invasive cancer were verified. Results Neither ATP hydrolysis nor E-NPP activity was changed by the neoplasia stage. On the other hand, ADP and AMP hydrolysis as well as ADA activity were enhanced in NIC I group. AMP hydrolysis was also increased in the cancer group. ADA 1 was the ADA isoform found in platelets from both control and patient groups. Conclusion Our results showed for the first time that NTPDase, 5′-nucleotidase, E-NPP and ADA are not sensible regarding the grade of neoplasia development, since no significant difference was found between the groups studied. Only ADP hydrolysis and ADA activity showed a significant enhancement in NIC I group related to the other stages possibly as a result of the beginning of the neoplasic transformation. This increase could be reflecting a body's reaction against the probable high adenosine levels. We propose for the first time that the ADA isoform present in platelets is ADA 1.

Introduction The thrombogenic process that affects the hypertensive patient is associated with regulatory mechanisms present in the vascular endothelium. These mechanisms involve release of an endothelium-derived relaxing factor, ectonucleotidase activity and calcium ion concentration. Methods Interference with ENTPDase activity in platelets of hypertensive patients and healthy donors was evaluated for arginine, sodium nitroprusside, and hydralazine. In addition, the kinetic behavior of NTPDase was determined in the presence of the vasodilator that showed the greatest inhibitory influence. Results Vasodilators decreased NTPDase activity with ATP and ADP as substrates. In controls, hydrolysis was increased in the presence of arginine. Captopril did not affect enzyme activities. The dose response for increasing sodium nitroprusside was biphasic. Kinetic behavior studies were estimated in the presence of sodium nitroprusside, which caused a mixed inhibition. The K m values increased and V max decreased with increasing sodium nitroprusside concentrations. The IC 50 and K i values indicated that the vasodilator was a strong NTPDase inhibitor when tested for the control and hypertensive group, using ATP and ADP as substrate, respectively. Conclusion It is postulated that there was an interaction between vasodilators, NO donors and inhibition of NTPDase.

Objective Ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) activities, in the platelets and serum, were examined in patients with uterine cervix neoplasia without treatment as well as in patients treated by conization or radiotherapy (RTX). Design and methods The patients were divided based on the amount of time from the end of the treatments until the day of the blood sampling. Groups I (n = 19) (conization) and III (n = 11) (radiotherapy) (treated from one to five years earlier), groups II (n = 19) (conization) and IV (n = 16) (radiotherapy) (treated recently; up to three months earlier) and the non-treated group (cancer) (n = 7). Results E-NPP and ADA in the platelets and E-NPP in the serum were decreased in all the treated groups in relation to the control and non-treated groups, while ADA in the serum was decreased only in the conization groups in relation to them. In group II, E-NPP and ADA, in the platelets, were increased in relation to group IV. Conclusion The tendency of reduction for E-NPP and ADA indicates that they may act together to control nucleotide levels and it may also be speculated that surgery causes greater platelet activation contributing to the changes seen in the conization groups. In this sense, platelets seem to be more sensitive than serum.

The nucleotide degrading enzymes, ectonucleotidases, present on the platelet surface of human pregnant with a normal (without complications) or high risk for thrombosis (hypertension and gestational diabetes) were studied. NTPDase (E.C. 3.6.1.5, CD39) and 5'-nucleotidase (E.C. 3.1.3.5, CD73) activities of four patient groups, non-pregnant (NP, n = 18), pregnant without complications (P, n = 25), pregnant with hypertension (HP, n = 15) and pregnant with gestational diabetes mellitus (GDP, n = 10), were analyzed. Increased NTPDase activities were observed in the groups P (37.0%, S.D. = 2.03 and 34.0%, S.D. = 3.19), HP (40.0%, S.D. = 3.32 and 56.0%, S.D. = 3.25) and GDP (23.0%, S.D. = 2.30 and 42.0%, S.D. = 2.26) in comparison to the control group NP (p < 0.01, S.D. = 1.92 and S.D. = 2.48) when ATP and ADP were used as substrate, respectively. AMP was used as substrate to determine the 5'-nucleotidase activities, which showed to be elevated in the groups P (45.0%, S.D. = 1.73), HP (54.0%, S.D. = 2.64) and GDP (68.0%, S.D. = 1.69) when compared to the control group NP (p < 0.01, S.D. = 1.26). However, no statistically significant differences were observed between the groups P, HP and GDP. As a consequence, the enhanced ATP, ADP and AMP hydrolysis was ascribed to the pregnancy itself, independent of a normal or high risk for thrombosis. The enhanced NTPDase and 5'-nucleotidase activities in platelets suggest that these enzymes are involved in the thromboregulation process in the pregnancy.

In this paper, we studied the influence of uremia and hemodialysis on oxidative parameters and delta-aminolevulinic acid dehydratase (delta-ALA-D) activity in control subjects, patients with chronic renal failure (CRF) on hemodialysis treatment (HD) and in patients not undergoing hemodialysis (ND). An increased lipid peroxidation was observed in the serum of HD and ND patients, as measured by the MDA serum levels. However, the level of MDA from erythrocytes was only elevated in HD patients. Blood catalase activity was increased in HD and ND groups. This study also showed a decreased activity of blood delta-aminolevulinic acid dehydratase (delta-ALA-D) in both groups of patients. This study demonstrated a positive correlation between ALA-D activity and hemoglobin, suggesting that inhibition of this enzyme might enhance anemia in CRF. A negative correlation was found between the alteration in delta-ALA-D activity and oxidative stress, which may indicate that the inhibition of ALA-D can be used as an index of oxidative stress.

Background Cervical cancer is a major cause of morbidity among women. We investigated the treatment effect on oxidative status from patients submitted to radiotherapy or conization surgery to high-grade SIL (squamous intraepithelial lesion) treatment, and oxidative profile from patients newly diagnosed for uterine cervix cancer, without treatment. Methods We determined the catalase activity in blood, reduced glutathione (GSH) in plasma, TBARS and protein carbonyl content from serum samples of the patients. Results The catalase activity, GSH levels, TBARS and protein carbonyl content had no statistical differences related to the controls, neither when the 2 treatments were compared, possibly because the antioxidant defense may be acting in the first period of the neoplasic transformation, and maybe indicating a possible arrest of the tumor cells caused by the efficiency of the treatments. In the non-treated patients, TBARS and protein carbonyl contents, GSH levels and catalase activity were shown to be increased comparing with the treated patients and compared with the controls indicating an tumor effect on oxidative profile, and the antioxidant activity been increased in the beginning of the tumor development. Conclusions We suggest that the treatments were efficient in arrest of the tumor.