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Brain and serum lipid peroxidation was studied in rats treated with vincristine sulphate and different doses of nandrolone decanoate. Thirty rats were distributed into six groups (n=5). The treatments were applied once a week for two weeks. Sample collection was performed in the third week. Treatments during the first week were: G1 (control) - physiologic solution, G2 - vincristine sulphate (4mg/m²), G3 - physiologic solution, G4 - physiologic solution, G5- vincristine sulphate (4mg/m²), and G6 - vincristine sulphate (4mg/m²). In the second week, they were: G1 (control) - physiologic solution, G2- physiologic solution, G3 - nandrolone decanoate (1.8mg/kg-1), G4 - nandrolone decanoate (10mg/kg-1), G5 - nandrolone decanoate (1.8mg/kg-1), and G6 - nandrolone decanoate (10mg/kg-1). Lipid peroxidation increased with the isolated use of vincristine and nandrolone decanoate, and with vincristine associated to the highest dose of the ester as well. These results suggest that vincristine sulphate and nandrolone decanoate increase free radical production. Therapeutic dose of nandrolone decanoate when associated with vincristine sulphate proved to be beneficial, as it was able to protect the organism from damaging processes involved in free radical production Este estudo teve por objetivo detectar a peroxidação lipídica presente no cérebro e no soro de ratos tratados com sulfato de vincristina e diferentes doses de decanoato de nandrolona. Trinta ratos foram distribuídos em seis grupos (n=5). Os tratamentos foram aplicados uma vez por semana, durante duas semanas, e a coleta de amostras foi realizada na terceira semana. Na primeira semana, os tratamentos consistiram de: G1(controle) - solução fisiológica; G2 - sulfato de vincristina (4mg/m 2 ); G3 - solução fisiológica; G4 - solução fisiológica; G5 - sulfato de vincristina (4mg/m 2 ) e G6 - sulfato de vincristina (4mg/m 2 ). Na segunda semana: G1(controle) - solução fisiológica; G2 - solução fisiológica; G3 - decanoato de nandrolona (1.8mg/kg-1 ); G4 - decanoato de nandrolona (10mg/kg-1 ); G5 - decanoato de nandrolona (1.8mg/kg-1 ) e G6 - decanoato de nandrolona (10mg/kg-1 ). A peroxidação lipídica aumentou com o uso isolado tanto da vincristina quanto do decanoato de nandrolona e com a associação da vincristina à dose mais alta do éster. Estes resultados sugerem que o sulfato de vincristina e o decanoato de nandrolona aumentam a produção de radicais livres. A dose terapêutica do decanoato de nandrolona, quando associada ao sulfato de vincristina, provou ser benéfica, já que foi capaz de proteger o organismo dos processos prejudiciais induzidos pela produção de radicais livres

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.

This study aimed to detect brain and red blood cell acetylcholinesterase activity (AChE and RBC-AChE, respectively) of rats treated with vincristine sulphate and different doses of nandrolone decanoate. Thirty rats were divided into six groups (n = 5). The treatments were applied once a week for 2 weeks. Sample collection was performed in the third week. The groups were divided in: G1, physiologic solution (PS) (first and second week); G2, vincristine sulphate (4 mg/m2) in the first week and PS in the second week; G3, PS in the first week and nandrolone decanoate (1.8 mg/kg−1) in the second week; G4, PS in the first week and nandrolone decanoate (10 mg/kg−1) in the second week; G5, vincristine sulphate (4 mg/m2) in the first week and nandrolone decanoate (1.8 mg/kg−1) in the second week; and G6, vincristine sulphate (4 mg/m2) in the first week and nandrolone decanoate (10 mg/kg−1) in the second week. The isolated use of nandrolone decanoate and its use in association with vincristine sulphate altered brain AChE and RBC-AChE activity. These results suggest that there is interference in cholinergic neurotransmission, which could cause an alteration of its neurotransmitter, as well as a low or high stimulation of post-synaptic receptors. The serum RBC-AChE activity results presented in this study are similar to those exhibited by brain tissue.

The aim of the present study was to investigate the effects of resveratrol (RV), an important neuroprotective compound on NTPDase, 5'-nucleotidase and acetylcholinesterase (AChE) activities in cerebral cortex synaptosomes of streptozotocin (STZ)-induced diabetic rats. The animals were divided into six groups (n=8): control/saline; control/RV 10mg/kg; control/RV 20mg/kg; diabetic/saline; diabetic/RV 10mg/kg; diabetic/RV 20mg/kg. After 30 days of treatment with resveratrol the animals were sacrificed and the cerebral cortex was removed for synaptosomes preparation and enzymatic assays. The results demonstrated that NTPDase and 5'-nucleotidase activities were significantly increased in the diabetic/saline group (p0.05) compared to control/saline group. Treatment with resveratrol significantly increased NTPDase, 5'-nucleotidase activities in the diabetic/RV10 and diabetic/RV20 groups (p0.05) compared to diabetic/saline group. When resveratrol was administered per se there was also an increase in the activities of these enzymes in the control/RV10 and control/RV20 groups (p0.05) compared to control/saline group. AChE activity was significantly increased in the diabetic/saline group (p0.05) compared to control/saline group. The treatment with resveratrol prevented this increase in the diabetic/RV10 and diabetic/RV20 groups. In conclusion, this study demonstrated that the resveratrol interfere with the purinergic and cholinergic neurotransmission by altering NTPDase, 5'-nucleotidase and AChE activities in cerebral cortex synaptosomes of diabetic rats. In this context, we can suggest that resveratrol should be considered potential therapeutics and scientific tools to be investigated in brain disorders associated with the diabetes.

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

The objective of the present study was to investigate the effect of the administration of resveratrol (RV) on memory and on acetylcholinesterase (AChE) activity in the cerebral cortex, hippocampus, striatum, hypothalamus, cerebellum and blood in streptozotocin-induced diabetic rats. The animals were divided into six groups (n=6-13): Control/saline; Control/RV 10 mg/kg; Control/RV 20 mg/kg; Diabetic/saline; Diabetic/RV 10 mg/kg; Diabetic/RV 20 mg/kg. One day after 30 days of treatment with resveratrol the animals were submitted to behavioral tests and then submitted to euthanasia and the brain structures and blood were collected. The results showed a decrease in step-down latency in diabetic/saline group. Resveratrol (10 and 20 mg/kg) prevented the impairment of memory induced by diabetes. In the open field test, no significant differences were observed between the groups. In relation to AChE activity, a significant increase in diabetic/saline group (P

Background Acute lymphoblastic leukemia (ALL) is a type of cancer that affects lymphocytes and it is the most common form of cancer in children. Acetylcholinesterase (AChE) is well known as having non-cholinergic functions and has been detected in the blood and plasma of humans including in lymphocytes. Thus, we investigated whole blood and lymphocyte AChE activity in patients with ALL. Methods This study was performed on 72 children with ALL divided into 4 groups: newly diagnosed, remission induction, remission maintenance and out-of-treatment and one control group of 50 healthy subjects. We determined AChE activity in whole blood and lymphocytes of these patients. Results Results demonstrated that whole blood AChE activity was enhanced in the newly diagnosed group and reduced in the remission induction and remission maintenance groups in relation to the control group. For lymphocyte AChE activity we found an increase in the newly diagnosed group and a decrease in the remission induction group in relation to the control. Conclusions These results suggest that AChE activity was altered in ALL patients. This fact may be related with the essential role played by AChE in the development of hematological disease and its contribution to the regulation of immune function.

Aims Diabetes mellitus is associated with platelet alterations that may contribute to the development of cardiovascular complications. The present study investigates the effects of resveratrol (RSV), an important compound with cardioprotective activities, on NTPDase, ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP), 5′-nucleotidase and adenosine deaminase (ADA) activities in platelets from streptozotocin (STZ)-induced diabetic rats. Main methods The animals were divided into six groups (n = 8): control/saline; control/RSV 10 mg/kg; control/RSV 20 mg/kg; diabetic/saline; diabetic/RSV 10 mg/kg; diabetic/RSV 20 mg/kg. RSV was administered during 30 days and after this period the blood was collected for enzymatic assay. Key findings The results demonstrated that NTPDase, E-NPP and 5′-nucleotidase activities were significantly higher in the diabetic/saline group (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.

The activity of the enzymes NTPDase and 5'-nucleotidase was studied in both diabetes mellitus and an associated model of iron-overload. Rats were divided in five groups: citrate (CC), saline (S), diabetic (D), iron-overload (IO), and diabetic iron-overload (DIO). Diabetes was induced with alloxan (150 mg/kg), and iron-overload was induced with iron-dextran (10 intramuscular applications of +/-80 mg/kg). The enzymatic activities were evaluated in the platelets. The results demonstrated an increase in the activity of NTPDase with substrates ATP and ADP (60% and 120%, respectively; P0.001), and 5'-nucleotidase (60%, P0.001). This increase was more intense in the IO and DIO groups. The results obtained in vitro showed an activation in ATP, ADP, and AMP hydrolysis between 1 microM and 1,000 microM ferric nitrate concentrations, being more pronounced at 100 microM and decreasing at 1,000 microM. We concluded that diabetes mellitus in association with iron-overload increased the hydrolysis of adenine nucleotides in platelets, contributing to the abnormalities found in these pathological conditions.

Kinetic parameters of the effect of tacrine as a cholinesterase inhibitor have been studied in two different sources: snake venom (Bungarus sindanus) acetylcholinesterase (AChE) and human serum butyrylcholinesterase (BChE). Tacrine inhibited both venom acetylcholinesterase (AChE) as well as human serum butyrylcholinesterase (BChE) in a concentration-dependent manner. Kinetic studies indicated that the nature of inhibition was mixed for both enzymes, i.e. Km values increase and Vmax decrease with the increase of the tacrine concentration. The calculated IC50 for snake venom and for human serum were 31 and 25.6 nM, respectively. Ki was observed to be 13 nM for venom acetylcholinesterase (AChE) and 12 nM for serum butyrylcholinesterase (BChE). KI (constant of AChE-ASCh-tacrine complex into AChE-ASCh complex and tacrine) was estimated to be 20 nM for venom and 10 nM for serum butyrylcholinesterase (BChE), while the gammaKm (dissociation constant of AChE-ASCh-tacrine complex into AChE-tacrine complex and ASCh) were 0.086 and 0.147 mM for snake venom AChE and serum BChE, respectively. The present results suggest that this therapeutic agent used for the treatment of Alzheimer's disease can also be considered an inhibitor of snake venom and human serum butyrylcholinesterase. Values of Ki and KI show that tacrine had more affinity with these enzymes as compared with other cholinesterases from the literature.

The ethidium bromide (EB) demyelinating model was associated with interferon beta (IFN-beta) to evaluate acetylcholinesterase (AChE) activity in the striatum (ST), hippocampus (HP), cerebral cortex (CC), cerebellum (CB), hypothalamus (HY), pons (PN) and synaptosomes from the CC. Rats were divided into four groups: I control (saline), II (IFN-beta), III (EB) and IV (EB and IFN-beta). After 7, 15 and 30 days rats (n = 6) were sacrificed, and the brain structures were removed for enzymatic assay. AChE activity was found to vary in all the brain structures in accordance with the day studied (7-15-30 days) (P0.05). In the group III, there was an inhibition of the AChE activity in the ST, CB, HY, HP and also in synaptosomes of the CC (P0.05). It was observed that IFN-beta per se was capable to significantly inhibit (P0.05) AChE activity in the ST, HP, HY and synaptosomes of the CC. Our results suggest that one of the mechanisms of action of IFN-beta is through the inhibition of AChE activity, and EB could be considered an inhibitor of AChE activity by interfering with cholinergic neurotransmission in the different brain regions.

The aqueous extract of Casearia sylvestris was tested in cortical membrane preparations. C. sylvestris was obtained commercially from two different sources, designated as Sample A and Sample B. The enzymes studied in this work were NTPDase-like, 5'-Nucleotidase, Na(+)/K(+)-ATPase and acetylcholinesterase (AChE). Adult rats received aqueous extracts from C. sylvestris in a dose of 20mg/kg body wt. daily for a 75-day-period, by oral administration (gavage). Our study showed that this treatment caused an inhibition of NTPDase-like activity with both, ATP (19.41% with Sample A and 25.03% with Sample B) and ADP (41.57% with Sample A and 31.20% with Sample B) as substrates. This treatment also caused an inhibition of 5'-nucleotidase activity (28.34% with Sample A and 31.46% with Sample B) and Na(+)/K(+)-ATPase (25.08% with Sample A and 24.81% with Sample B). The rate of acetylcholine degradation was reduced, as shown by the inhibition of AChE (31.65% and 26.74%, Samples A and B, respectively). These results suggest that extracts of C. sylvestris can cause neurochemical alterations in the purinergic and cholinergic systems of the central nervous system.

Apyrase and 5'-nucleotidase activities were analyzed in an ethidium bromide (EB) demyelinating model associated with interferon-beta (IFN-beta). The animals were divided in groups: I, control (saline); II, saline and IFN-beta; III, EB and IV, EB and IFN-beta. After 7, 15 and 30 days the animals (n = 5) were sacrificed and the cerebral cortex was removed for synaptosome preparation and enzymatic assays. Apyrase activity using ATP as substrate increased in groups II, III and IV (P0.001) after 7 days and in groups III and IV (P0.001) after 15 days. Using ADP as substrate, an activation of this enzyme was observed in group III (P0.05) after seven and 15 days. The 5'-nucleotidase activity increased in group III (P0.05) after 7 days and in groups II, III and IV (P0.001) after 15 days. After 30 days treatment, no significant alteration was observed in enzyme activities. Results showed that apyrase and 5'-nucleotidase activities are altered in demyelination events and that IFN-beta was able to regulate the adenine nucleotide hydrolysis.

The activities of the enzymes NTPDase (E.C.3.6.1.5, apyrase, ATP diphosphohydrolase, ecto-CD39) and 5′-nucleotidase (E.C.3.1.3.5, CD73) were analyzed in platelets from patients with chronic renal failure (CRF), both undergoing hemodialysis treatment (HD) and not undergoing hemodialysis (ND), as well as from a control group. The results showed an increase in platelet NTPDase activity in CRF patients on HD treatment (52.88%) with ATP as substrate (P

Aluminum (Al), oxidative stress and impaired cholinergic functions have all been related to Alzheimer's disease (AD). The present study evaluates the effect of aluminum on acetylcholinesterase (AChE) and lipid peroxidation in the mouse brain. Mice were loaded by gavage with Al 0.1 mmol/kg/day 5 days per week during 12 weeks. The mice were divided into four groups: (1) control; (2) 10 mg/mL of citrate solution; (3) 0.1 mmol/kg of Al solution; (4) 0.1 mmol/kg of Al plus 10 mg/mL of citrate solution. AChE activity was determined in the hippocampus, striatum, cortex, hypothalamus and cerebellum and lipid peroxidation was determined in the hippocampus, striatum and cortex. An increase of AChE activity was observed in the fourth group (Al + Ci) in the hippocampus (36%), striatum (54%), cortex (44%) and hypothalamus (22%) (p

To evaluate the effect of N-acetylcysteine (NAC), a potent ROS scavenger and thiol group supplier, on normoglycemic and diabetic rats, the animals received 50 or 200 mg/kg NAC by gavage daily for 45 days. The results showed a lack of uniformity in acetylcholinesterase activity among the four cerebral structures. While neither dose of NAC produced significant hypoglycemic activity, 50 mg/kg NAC partially reverted the weight loss of diabetics and was effective in restoring aminolevulinate dehydratase activity and non-protein thiol content in liver, and in diminishing serum protein carbonylation. The dose of 200 mg/kg NAC presented some negative effects per se in both the antioxidant and cholinergic systems. In conclusion, 50 mg/kg NAC produced an improvement in some parameters suggesting NAC as a possible drug in antioxidant therapies against diabetic state. However, future studies are necessary to investigate the better dose of this compound to counteract its undesirable effects.

Von Willebrand disease (VWD) is one of the most common inherited bleeding diseases caused by a qualitative or quantitative deficiency of the von Willebrand factor (FvW). FvW is a multimeric glycoprotein synthesized by megakaryocytes and endothelial cells and it is present in the subendothelial matrix, blood plasma, platelets, and endothelium. This glycoprotein plays an important role in thrombus formation by initiating platelet adhesion to sites of injury as well as platelet aggregation. The aim of this study was to evaluate the activities of enzymes that hydrolyze adenine nucleotides in platelets, ristocetin-induced platelet aggregation (RIPA), and polymorphisms of the alpha2 gene of alpha2beta1 integrin from VWD patients. Platelet nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase, and ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP) activities were verified in 14 VWD patients. For RIPA determination, a final concentration of 1.25 mg/ml of ristocetin was used. Polymorphisms of the alpha2 gene were analyzed through PCR. Platelet NTPDase and E-NPP were decreased in VWD patients. 5'-Nucleotidase activity was not statistically significant between controls and VWD patients. RIPA was significantly reduced, with an allelic frequency of 78.57% for 807C in VWD patients. Our results indicated reduced platelet NTPDase and E-NPP activities which might be related to the low platelet adhesiveness. The prevalence of the 807C allele might account for the variability in bleeding in VWD.

Background Multiple sclerosis (MS) is a demyelinating neurological disease, which is presumed to be a consequence of infiltrating lymphocytes that are autoreactive to myelin proteins. ATP and adenosine contribute to fine-tuning immune responses and NTPDase (CD39) and adenosine deaminase (ADA) are important enzymes in the control of the extracellular levels of these molecules at the site of inflammation. We evaluated the activity and expression of NTPDase and adenosine deaminase (ADA) activity in lymphocytes from patients with the relapsing–remitting form of MS (RRMS). Methods This study involved 22 patients with RRMS and 22 healthy subjects as a control group. The lymphocytes were isolated from blood and separated on Ficoll density gradients and after isolation the NTPDase and ADA activities were determined. Results The NTPDase activity and expression were increased in lymphocytes from RRMS patients when compared with the control group (p

Multiple sclerosis (MS) is the most common chronic disabling neurological disease in young adults. Alterations in platelet function have been observed in MS; however, the mechanism and the relevance of this blood cell disorder with regard to MS pathogenesis are not yet understood. The aim of this study was to evaluate activities of ectonucleoside thiphosphate diphosphohydrolase (NTPDase, CD39), ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP), 5′-nucleotidase and adenosine deaminase (ADA) in platelets from patients with the relapsing–remitting form of MS (RRMS), as well as to analyze platelet aggregation and expression of NTPDase. The results obtained show that NTPDase, 5′-nucleotidase, E-NPP and ADA activities were decreased in platelets of RRMS patients when compared with the control group (p < 0.05). In addition, NTPDase expression in platelets was also decreased in these patients (p < 0.05); however, no differences were observed in platelet aggregation between RRMS patients and the control group. Our results suggest that the alterations in NTPDase, E-NPP, 5′-nucleotidase and ADA may have contributed to the alterations in platelet function in MS by altering the levels of nucleotides and nucleosides in the circulation.

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.

The ethidium bromide (EB) demyelinating model was associated with vitamin E (Vit E) and ebselen (Ebs) treatment to evaluate acetylcholinesterase (AChE) activity in the striatum (ST), hippocampus (HP), cerebral cortex (CC) and erythrocytes. Rats were divided into seven groups: I-Control (saline), II-(canola); III-(Ebs), IV-(Vit E); V-(EB); VI-(EB+Ebs) and VII-(EB+Vit E). At 3 days after the EB injection, AChE activity in the CC and HC was significantly reduced in groups III, IV, V, VI and VII (p

Aluminum (Al), a neurotoxic agent, has been associated with Alzheimer’s disease (AD), which is characterized by cholinergic dysfunction in the central nervous system. In this study, we evaluated the effect of long-term exposure to aluminum on acetylcholinesterase (AChE) activity in the central nervous system in different brain regions, in synaptosomes of the cerebral cortex and in erythrocytes. The animals were loaded by gavage with AlCl3 50 mg/kg/day, 5 days per week, totalizing 60 administrations. Rats were divided into four groups: (1) control (C); (2) 50 mg/kg of citrate solution (Ci); (3) 50 mg/kg of Al plus citrate (Al + Ci), and (4) 50 mg/kg of Al (Al). AChE activity in striatum was increased by 15% for Ci, 19% for Al + Ci and 30% for Al, when compared to control (P

The objective of this work was to evaluate the effect of different glucose levels on the ATP, ADP and AMP hydrolysis in the platelets of diabetic, hypertensive and diabetic/hypertensive participants.The activities of the enzymes NTPDase (ATP and ADP hydrolysis) and 5'-nucleotidase (AMP hydrolysis), and CD39 expression were analyzed in human blood platelets of diabetic (DM-2), hypertensive (HT) and diabetic/hypertensive (DM-2/HT) patients. To evaluate the interference of glucose and fructose in NTPDase and 5'-nucleotidase activities, experiments were performed with glucose, fructose and mannitol concentrations ranging from 5 to 30 mM in platelet-rich plasma (PRP). Pre-incubation times of 10, 120 min and 24h were used.NTPDase and 5'-nucleotidase activities increased with increasing glucose and fructose concentrations (P0.001) and the different times of pre-incubation did not interfere in ectonucleotidases activities (P0.5). NTPDase and 5'-nucleotidase activities demonstrated a positive correlation between serum glucose levels and ATP and ADP hydrolysis in DM-2 and DM-2/HT patients. CD39 expression demonstrated that DM-2, HT and DM-2/HT groups presented a significant increase when compared to the control group (P0.004).The hydrolysis of adenine nucleotides is enhanced in platelets of patients with diabetes and hypertension. We observed that an increasing glucose concentration had a direct effect on ATP, ADP and AMP hydrolysis. Furthermore, CD39 expression was enhanced in all patients groups, indicating that these enzyme activities are related with diabetes and hypertension.

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.

Aluminium (Al), a neurotoxic compound, has been investigated in a large number of studies both in vivo and in vitro. In this study, we investigated the effect in vivo of long-term exposure to Al on NTPDase (nucleoside triphosphate diphosphohydrolase) and 5'-nucleotidase activities in the synaptosomes (obtained from the cerebral cortex and hippocampus) and platelets of rats. Here, we investigated a possible role of platelets as peripheral markers in rats. Rats were loaded by gavage with AlCl(3) 50 mg/(kg day), 5 days per week, totalizing 60 administrations. The animals were divided into four groups: (1) control (C), (2) 50 mg/kg of citrate solution (Ci), (3) 50 mg/kg of Al plus citrate (Al+Ci) solution and (4) 50 mg/kg of Al (Al). ATP hydrolysis was increased in the synaptosomes from the cerebral cortex by 42.9% for Al+Ci and 39.39% for Al, when compared to their respective control (p0.05). ADP hydrolysis was increased by 13.15% for both Al and Al+Ci, and AMP hydrolysis increased by 32.7% for Al and 27.25% for Al+Ci (p0.05). In hippocampal synaptosomes, the hydrolysis of ATP, ADP and AMP, was increased by 58.5%, 28.5% and 25.92%, respectively, for Al (p0.05) and 36.7%, 22.5% and 37.64% for Al+Ci, both when compared to their respective controls. ATP, ADP and AMP hydrolysis, in platelets, was increased by 172.3%, 188.52% and 92.1%, respectively in Al+Ci, and 317.9%, 342.8% and 177.9%, respectively, for Al, when compared to their respective controls (p0.05). Together, these results indicate that Al increases NTPDase and 5'-nucleotidase activities, in synaptosomal fractions and platelets. Thus, we suggest that platelets could be sensitive peripheral markers of Al toxicity of the central nervous system.

Carbofuran and malathion, well known pesticides, and paraquat, a world widely used herbicide, were tested on acetylcholinesterase (AChE) from Bungarus sindanus venom and butyrylcholinesterase (BChE) from human serum. The calculated IC(50 )values for inhibition of venom enzyme by malathion, carbofuran and paraquat were 2.5, 0.14, and 0.16 microM, respectively. The values for inhibition of serum butyrylcholinesterase (BChE) were 3.5, 0.09 and 0.18 microM, respectively. Analysis of kinetic data indicated that the inhibition caused by malathion, carbofuran and paraquat was mixed for venom AChE. For BChE from human serum, the inhibition caused by malathion and paraquat was mixed and for carbofuran it was uncompetitive. The present results suggest a commercial paraquat preparation (a popular herbicide) inhibits cholinesterases with similar or higher potency than classical pesticide inhibitors. Furthermore, this inhibition was observed both in human serum and snake venom, a newly studied source of AChE.

In the present study we investigated a potential mechanism by which high sugar (HS) and high fat (HF) diets could affect acetylcholinesterase (AChE) activity. The treatment with HS and HF diet was done for six months on male and female rats. The results showed decreased hippocampal AChE activity in male and females receiving HS and HF diets (HS 24% and 36%; HF 38% and 32%, males and females, respectively; P < 0.05). The activity in the cerebral cortex was reduced in males (49 and 40%) and females (19 and 17%) (P < 0.05) on HS and HF diets, respectively. In the hypothalamus AChE activity was decreased on HS diet in males (46%) and female (25%) (P < 0.05) and also on HF diet in males (34%) and females (21%) (P < 0.05). However, in the cerebellum no changes in AChE activity were observed. These results indicate that HS and HF diets produced mainly inhibition in acetylcholine degradation. It probably indicates a chronic alteration induced by these diets on the cholinergic system.

The present study verified the efficiency of the bark ethanol extract of Syzygium cumini on the cholinergic system of normal and alloxan induced diabetic rats. Thirty-nine female rats were divided in control (C), treated with Syzygium cumini (TS), diabetic (D) and diabetic treated with Syzygium cumini (DS). The activity of acetylcholinesterase (AChE) was analyzed in the following cerebral structures: cerebellum, cortex, striatum and hippocampus. The extract of the bark of Syzygium cumini in the dose of 1g.kg-1 was administered orally daily for a period of thirty days. After this period the extract inhibited the activity of the AChE in the cerebellum and cerebral cortex of the rats in the DS group (P

The organophosphorus insecticides, including malathion, are used indiscriminately in large amounts, causing environmental pollution and risk to human health. Classically, this toxicity is attributed mainly to the accumulation of acetylcholine (ACh), due to inhibition of acetylcholinesterase (AChE), and consequently overstimulation of the nicotinic and muscarinic receptors. The present study investigated the effects of acute and chronic malathion administration in immobility time in the forced swimming test (FST), open-field test and AChE activity in neural tissue of rats. Malathion was administered intraperitoneally once a day for one day (acute) or for 28 days (chronic) (in both protocols malathion was administered at 25, 50, 100 and 150 mg/kg). No significant effect was seen in immobility time in the FST after acute malathion treatment. The chronic malathion treatment induced an increase in the time of immobility in the FST. Both treatments do not interfere in locomotor activity evaluated in a novel environment. The inhibition of AChE activity was significant in the hippocampus (25, 50, 100 and 150 mg/kg), cortex (100 and 150 mg/kg) and striatum (150 mg/kg) after chronic treatment, but not significantly after acute treatment. These data suggest a possible interaction between increased immobility time in the FST and activation of cholinergic receptors by accumulated ACh subsequent to AChE inhibition.