Effects of a physical exercise or motor activity protocol on cognitive function, lipid profile, and BDNF levels in older adults with mild cognitive impairment.

This study analyzed the effects of a physical exercise program compared to the complexity of the motor task on the cognitive function, brain-derived neurotrophic factor (BDNF) levels, and lipid profile of older adults with mild cognitive impairment (MCI). Twenty-seven participants were randomized into three intervention groups: Physical Exercise (PE), Motor Task (MT), and Physical Exercise associated with Motor Task (PE + MT). Six months of intervention twice a week resulted in improvements in cognitive function, total cholesterol (TC), and LDL cholesterol (LDL-C) in the PE (p < 0.05). In the PE + MT, in addition to improved cognitive capacity, there was also a reduction in non-HDL cholesterol (NHDL-C) and LDL cholesterol (LDL-C) levels (p < 0.05), while in the MT, the values of TC, NHDL-C, and LDL-C decreased as a result of the intervention. BDNF levels were not affected by the interventions. In conclusion, PE alone or combined with MT is effective in promoting improvements in overall cognitive function and lipid profile in older adults with MCI; and BDNF seems not to be a sensitive marker for people with mild cognitive impairment.

Modulation of Inflammatory Mediators and Microglial Activation Through Physical Exercise in Alzheimer's and Parkinson's Diseases.

Neuroinflammation is an inflammatory process in the central nervous system (CNS), in addition to being one of the main features of Alzheimer's disease (AD) and Parkinson's disease (PD). Microglia are known for their immune functions and have multiple reactive phenotypes related to the types of stages involving neurodegenerative diseases. Depending on the state of activation of microglia in the CNS, it can be neuroprotective or neurotoxic. In this context, AD is a neurodegenerative and neuroinflammatory disease characterized by the deposition of beta-amyloid plaques, formation of fibrillar tangles of tau protein, and loss of neurons due to neurotoxic activation of microglia. However, PD is characterized by the loss of dopaminergic neurons in the substantia nigra and accumulation of alpha-synuclein in the cortical regions, spinal cord, and brain stem, which occurs by microglial activation, contributing to the neuroinflammatory process. In this aspect, the activation of microglia in both pathologies triggers high levels of inflammatory markers, such as interleukins, and causes the neuroinflammatory process of the diseases. Thus, physical exercise is pointed out as neuroprotective, as it can act to strengthen neurogenesis and reduce the inflammatory process. Therefore, the present review addresses the neuroprotective effect of microglia after different types of physical exercise protocols and evaluates the activity and effects of inflammatory and anti-inflammatory parameters and mechanisms of AD and PD. This review will discuss the anti-inflammatory effects of physical exercise through microglia activation with neuroprotective activity and the role of pro-and anti-inflammatory cytokines in AD and PD.

The purinergic signalling and inflammation in the pathogenesis and progression of diabetes: key factors and therapeutic targets.

Type 2 diabetes mellitus (T2DM) is an important chronic disease around the world, and according to the World Health Organization, it is the 9th principal cause of global death. This pathology is characterized by high levels of circulating glucose as a result of insulin resistance, and it is well stated that inflammation related to obesity is directly associated with the development of the disease. The purinergic signalling is involved in both pancreatic destruction, which impairs insulin secretion, and the cytokine production that favors insulin resistance in T2DM. In this review, the purinergic signalling aspects will be discussed, showing the impact of the enzymes, nucleotides, nucleosides, and receptors of this system and the cytokines that result in inflammation, in the development and progression of T2DM, besides, pointing the purinergic receptors as a possible therapeutic approach.

Inflammatory profile in cervical cancer: influence of purinergic signaling and possible therapeutic targets.

INTRODUCTION AND OBJECTIVE: Cervical cancer is the fourth most prevalent type of cancer in the world. The tumor microenvironment of this disease is associated with the production of several cytokines, pro and anti-inflammatory, and with the purinergic signaling system so that changes in these components are observed throughout the pathological process. The aim of this review is to understand the pathophysiology of cervical cancer based on immunological processes and purinergic signaling pathways, in addition to suggesting possibilities of therapeutic targets. MATERIALS AND METHODS: To make up this review, studies covering topics of cervical cancer, inflammation and purinergic system were selected from the Pubmed. RESULTS: The main pro-inflammatory cytokines involved are IL-17, IL-1ß, IL-6, and IL-18, and among the anti-inflammatory ones, IL-10 and TGF-ß stand out. As new therapeutic targets, P2X7 and A2A receptors have been suggested, since blocking P2X7 would lead to reduced release of pro-inflammatory cytokines, and blocking A2A would increase activation of cytotoxic T lymphocytes in the context of tumor combat. The association between the immune system and the purinergic system, already known in other types of disease, also presents possibilities for a better understanding of biomolecular processes and therapeutic possibilities in the context of cervical cancer.

Effects of time-restricted feeding in weight loss, metabolic syndrome and cardiovascular risk in obese women.

BACKGROUND: The increasing prevalence of overweight and obesity among the worldwide population has been associated with a range of adverse health consequences such as Type 2 diabetes and cardiovascular diseases. The metabolic syndrome (MetS) is a cluster of cardiometabolic abnormalities that occur more commonly in overweight individuals. Time-restricted feeding (TRF) is a dietary approach used for weight loss and overall health. TRF may be an option for those subjects who struggle with extreme restriction diets with foods that generally do not belong to an individual's habits. OBJECTIVE: The purpose of this study was to determine the effect of TRF on body composition and the association of weight loss with metabolic and cardiovascular risks in obese middle-aged women. METHODS: A non-randomized controlled clinical trial was performed over 3 months in obese women (TRF group, n = 20, BMI 32.53 ± 1.13 vs. Control n = 12, BMI 34.55 ± 1.20). The TRF protocol adopted was 16 h without any energy intake followed by 8 h of normal food intake. MAIN OUTCOMES AND MEASURES: Anthropometric measurements, body composition, blood biomarkers, cardiovascular risk in 30 years (CVDRisk30y), and quality of life were evaluated at baseline and after the 3 months. RESULTS: TRF was effective in reducing weight (~ 4 kg), BMI, % of body fat (%BF), waist circumference from baseline without changes in blood biomarkers associated with MetS. TRF promoted a reduction in CVDRisk30y (12%) wich was moderately correlated with %BF (r = 0.62, n = 64, p < 0.001) and %MM (r = - 0.74, n = 64, p < 0.001). CONCLUSIONS: TRF protocol reduces body weight without changes in biomarkers related to MetS. In addition, the anthropometric evaluation that predicts %BF and %MM could be used as an approach to follow individuals engaged in the TRF regimen since they correlate with cardiovascular risk.

Possible role of purinergic signaling in COVID-19.

The coronavirus disease (COVID-19), caused by SARS-CoV-2 infection, accounts for more than 2.4 million deaths worldwide, making it the main public health problem in 2020. Purinergic signaling is involved in the pathophysiology of several viral infections which makes the purinergic system a potential target of investigation in COVID-19. During viral infections, the ATP release initiates a cascade that activates purinergic receptors. This receptor activation enhances the secretion of pro-inflammatory cytokines and performs the chemotaxis of macrophages and neutrophils, generating an association between the immune and the purinergic systems. This review was designed to cover the possible functions of purinergic signaling in COVID-19, focusing on the possible role of purinergic receptors such as P2X7 which contributes to cytokine storm and inflammasome NLRP3 activation and P2Y1 that activates the blood coagulation pathway. The possible role of ectonucleotidases, such as CD39 and CD73, which have the function of dephosphorylating ATP in an immunosuppressive component, adenosine, are also covered in detail. Moreover, therapeutic combination or association possibilities targeting purinergic system components are also suggested as a possible useful tool to be tested in future researches, aiming to unveil a novel option to treat COVID-19 patients.

Purinergic signaling as a new mechanism underlying physical exercise benefits: a narrative review.

In the last years, it has become evident that both acute and chronic physical exercise trigger responses/adaptations in the purinergic signaling and these adaptations can be considered one important mechanism related to the exercise benefits for health improvement. Purinergic system is composed of enzymes (ectonucleotidases), receptors (P1 and P2 families), and molecules (ATP, ADP, adenosine) that are able to activate these receptors. These components are widely distributed in almost all cell types, and they respond/act in a specific manner depending on the exercise types and/or intensities as well as the cell type (organ/tissue analyzed). For example, while acute intense exercise can be associated with tissue damage, inflammation, and platelet aggregation, chronic exercise exerts anti-inflammatory and anti-aggregant effects, promoting health and/or treating diseases. All of these effects are dependent on the purinergic signaling. Thus, this review was designed to cover the aspects related to the relationship between physical exercise and purinergic signaling, with emphasis on the modulation of ectonucleotidases and receptors. Here, we discuss the impact of different exercise protocols as well as the differences between acute and chronic effects of exercise on the extracellular signaling exerted by purinergic system components. We also reinforce the concept that purinergic signaling must be understood/considered as a mechanism by which exercise exerts its effects.

Oxidative damage and antioxidants in cervical cancer.

The pathogenesis of cervical cancer is related to oxidative damage caused by persistent infection by one of the oncogenic types of human papillomavirus (HPV). This damage comes from oxidative stress, which is the imbalance caused by the increase in reactive oxygen and nitrogen species and impaired antioxidant mechanisms, promoting tumor progression through metabolic processes. The incorporation of HPV into the cellular genome leads to the expression of oncoproteins, which are associated with chronic inflammation and increased production of reactive oxygen species, oxidizing proteins, lipids and DNA. The increase in these parameters is related, in general, to the reduction of circulating levels of enzymatic antioxidants-superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase; and non-enzymatic antioxidants-reduced glutathione, coenzyme Q10 and vitamins A, C and E, according to tumor staging. In contrast, some enzymatic antioxidants suffer upregulation in the tumor tissue as a way of adapting to the oxidative environment generated by themselves, such as glutathione-S-transferase, reduced glutathione, glutathione peroxidase, superoxide dismutase 2, induced nitric oxide synthase, peroxiredoxins 1, 3 and 6, and thioredoxin reductase 2. The decrease in the expression and activity of certain circulatory antioxidants and increasing the redox status of the tumor cells are thus key to cervical carcinoma prognosis. In addition, vitamin deficit is considered a possible modifiable risk factor by supplementation, since the cellular functions can have a protective effect on the development of cervical cancer. In this review, we will discuss the impact of oxidative damage on cervical cancer progression, as well as the main oxidative markers and therapeutic potentialities of antioxidants.

Purinergic signaling and tumor microenvironment in cervical Cancer.

Cervical cancer is the fourth most common type of cancer incidence in the world female population, and it has become a public health problem worldwide. Several factors are involved in this type of cancer, including intrinsic factors related to the inflammatory process, such as extracellular nucleotides and adenosine-components of the purinergic system. The present review focuses on the role of the purinergic system in cervical cancer, especially regarding the interaction of extracellular nucleotides with their respective receptors expressed in the tumor microenvironment of cervical cancer and their role in the host immune response. The high concentrations of extracellular nucleotides in the tumor microenvironment of cervical cancer interfere in the regulation, proliferation, differentiation, and apoptosis of cancer cells of the uterine cervix through different P1 and P2 receptor subtypes. Such diverse cellular processes that are mediated by adenosine triphosphate and adenosine across the tumor microenvironment and that also have effects on host immune defense will be reviewed here in detail.

Resistance training affects the hemodynamic parameters of hypertensive and normotensive women differently, and regardless of performance improvement.

BACKGROUND: Although the positive effects of resistance training (RT) on strength and functional capacity have been well evidenced in the scientific literature, the effects of RT on blood pressure and the relationship of these responses with performance improvement are not yet well established. OBJECTIVE: This study aimed to analyze the effects of three and six months of RT on the hemodynamic parameters and functional capacity of hypertensive and normotensive women. METHOD: Sixteen hypertensive and 15 normotensive elderly women participated in a RT protocol designed to increase muscle strength and hypertrophy, lasting six months, twice a week. RESULTS: Systolic blood pressure (SBP) had a reduction at six months only in hypertensive patients, while diastolic blood pressure (DBP) decreased at six months of intervention in both groups (p < 0.05). SBP showed differences between the groups in the pretest (p < 0.05), but not at three and six months of intervention (p > 0.05). Heart rate (HR) was reduced at three months in hypertensive patients, and at six months in the normotensive (p < 0.05). The strength and functional mobility of both hypertensive and normotensive individuals significantly increased at three and six months of intervention (p < 0.05). Hypertensive women showed increased strength at all moments, while normotensive ones showed improvement only at six months. CONCLUSION: Moderate to high intensity RT improves the hemodynamic parameters of hypertensive and normotensive women differently, and independently of strength gain and functional capacity improvement.

Physical exercise prevents alterations in purinergic system and oxidative status in lipopolysaccharide-induced sepsis in rats.

Sepsis is a generalized infection that involves alterations in inflammatory parameters, oxidant status, and purinergic signaling in many tissues. Physical exercise has emerged as a tool to prevent this disease because of its anti-inflammatory and antioxidant properties. Thus, in this study, we investigated the effects of physical exercise on preventing alterations in purinergic system components, oxidative stress, and inflammatory parameters in lipopolysaccharide (LPS)-induced sepsis in rats. Male Wistar rats were divided into four groups: control, exercise (EX), LPS, and EX+LPS. The resisted physical exercise was performed for 12 weeks on a ladder with 1 m height. After 72 hours of the last exercise session, the animals received 2.5 mg/kg of LPS for induction of sepsis, and after 24 hours, lungs and blood samples were collected for analysis. The results showed that the exercise protocol used was able to prevent, in septic animals: (1) the increase in body temperature; (2) the increase of lipid peroxidation and reactive species levels in the lung, (3) the increase in adenosine triphosphate levels in serum; (4) the change in the activity of the enzymes ectonucleotidases in lymphocytes, partially; (5) the change in the density of purinergic enzymes and receptors in the lung, and (6) the increase of IL-6 and IL-1ß gene expression. Our results revealed the involvement of purinergic signaling and oxidative damage in the mechanisms by which exercise prevents sepsis aggravations. Therefore, the regular practice of physical exercise is encouraged as a better way to prepare the body against sepsis complications.

High levels of extracellular ATP lead to chronic inflammatory response in melanoma patients.

Skin cancer represents a serious public health problem and melanoma is considered the most significant due to its high metastasis capacity. Evasion mechanisms are the main characteristic of these tumor cells to escape of immune response. Extracellular nucleotides and nucleosides play an important role in inflammatory and immune responses. In this study, we analyzed the expression and activity of purinergic system enzymes in platelets and lymphocytes, ATP levels quantification, as well the level of pro and anti-inflammatory interleukins in the serum of 23 patients with surgical melanoma removal (CM group) and 23 control subjects (CT group). Results showed a decrease in ATP, ADP, and AMP hydrolysis and an increase in ATP levels quantification in CM group. The pro-inflammatory cytokines were elevated in CM group when compared to CT group. These results suggest an inflammatory process, even after surgical removal, due to elevated extracellular ATP levels. Besides, CM group displayed an increase in IL-10 levels and an increased in ADA activity in platelets and lymphocytes. Once adenosine and IL-10 are anti-inflammatory molecules, these results indicate a down-regulation of immune system front to malignant process. The alteration in nucleotide and nucleoside hydrolysis reinforces the purinergic systems role in this cancer. Therefore, even after surgical removal, the purinergic system can develop a chronic inflammatory micro-environment that can influence directly on relapse or metastasis.

Acute responses of hemodynamic and oxidative stress parameters to aerobic exercise with blood flow restriction in hypertensive elderly women.

Systemic arterial hypertension has been associated with the majority deaths from cardiovascular disease, especially among the elderly population, and the imbalance between antioxidant and pro-oxidants has been associated with hypertension. This study analyzed the acute responses of cardiorespiratory and oxidative stress parameters to low intensity aerobic exercise (LIAE) with blood flow restriction (BFR) in hypertensive elderly women. The experimental group consisted of 16 hypertensive women (67.2 ± 3.7 years) who underwent a progressive treadmill test and performed three exercise protocols in random order: high intensity (HIAE), low intensity aerobic exercise (LIAE) and low intensity aerobic exercise with blood flow restriction (LIAE + BFR). Data analysis showed that blood pressure and heart rate augmented from rest to post effort (p < 0.05) and reduced from post effort to recovery (p < 0.05) in all protocols. The values of lipid peroxidation were higher after 30 min of recovery when compared to the moment at rest in the LILIAE + BFR (p < 0.05). The same occurred with glutathione-S-transferase and superoxide dismutase activity. However, non-protein thiols levels (NPSH) reduced after 30 min of recovery when compared to the moment at rest in the LILIAE + BFR protocol (p < 0.05). In the HIAE and LIAE + BFR protocols, the levels of NPSH were lower at 30 min of recovery when compared to the same moment in the LIAE protocol (p < 0.05). LIAE + RBF produces an oxidative status and hemodynamic stimulus similar to HIAE. Taken together, these results support the indication of LIAE with BFR in chronic intervention protocols, with potential benefits for the hypertensive elderly population.

Hypothyroidism Enhanced Ectonucleotidases and Acetylcholinesterase Activities in Rat Synaptosomes can be Prevented by the Naturally Occurring Polyphenol Quercetin.

Thyroid hormones have an influence on the functioning of the central nervous system. Furthermore, the cholinergic and purinergic systems also are extensively involved in brain function. In this context, quercetin is a polyphenol with antioxidant and neuroprotective properties. This study investigated the effects of (MMI)-induced hypothyroidism on the NTPDase, 5'-nucleotidase, adenosine deaminase (ADA), and acetylcholinesterase (AChE) activities in synaptosomes of rats and whether the quercetin can prevent it. MMI at a concentration of 20 mg/100 mL was administered for 90 days in the drinking water. The animals were divided into six groups: control/water (CT/W), control/quercetin 10 mg/kg, control/quercetin 25 mg/kg, methimazole/water (MMI/W), methimazole/quercetin 10 mg/kg (MMI/Q10), and methimazole/quercetin 25 mg/kg (MMI/Q25). On the 30th day, hormonal dosing was performed to confirm hypothyroidism, and the animals were subsequently treated with 10 or 25 mg/kg quercetin for 60 days. NTPDase activity was not altered in the MMI/W group. However, treatment with quercetin decreased ATP and ADP hydrolysis in the MMI/Q10 and MMI/Q25 groups. 5'-nucleotidase activity increased in the MMI/W group, but treatments with 10 or 25 mg/kg quercetin decreased 5'-nucleotidase activity. ADA activity decreased in the CT/25 and MMI/Q25 groups. Furthermore, AChE activity was reduced in all groups with hypothyroidism. In vitro tests also demonstrated that quercetin per se decreased NTPDase, 5'-nucleotidase, and AChE activities. This study demonstrated changes in the 5'-nucleotidase and AChE activities indicating that purinergic and cholinergic neurotransmission are altered in this condition. In addition, quercetin can alter these parameters and may be a promising natural compound with important neuroprotective actions in hypothyroidism.

Vitamin D3 prevents the increase in ectonucleotidase activities and ameliorates lipid profile in type 1 diabetic rats.

This study was designed to assess the potential effect of vitamin D3 (VD3) in avoiding atherothrombosis by modulation of lipid metabolism and platelet activation in type 1 diabetic rats. Male wistar rats were divided into eight groups (n = 5-10): Control/Saline (Sal); Control/Metformin 500 mg/kg (Metf); Control/Vitamin D3 90 µg/kg (VD3); Control/Metformin 500 mg/kg + VD3 90 µg/kg (Metf + VD3); Diabetic/Saline (Sal); Diabetic/Metformin 500 mg/kg (Metf); Diabetic/Vitamin D3 90 µg/kg (VD3); Diabetic/Metformin 500 mg/kg + VD3 90 µg/kg (Metf + VD3). Treatments were administered during 30 days after diabetes induction with streptozotocin (STZ). After 31 days, the rats were euthanized and blood was collected and separated into serum and platelets, both used for lipid profile and ectonucleotidase activity assays, respectively. Ectonucleoside triphosphate phosphohydrolase (E-NTPDase), ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP), and 5'-nucleotidase and adenosine deaminase (E-ADA) were significantly higher in the Diabetic than in Control group. Treatment with Metf and/or VD3 prevented the increase in NTPDase and E-NPP activities in diabetic rats. Only Metf + VD3 significantly prevented the increase in 5'-nucleotidase. VD3 alone, but not Metf, prevented the increase in ADA activity when compared to saline-treated diabetic rats. Treatment of rats with VD3, Metf, and Metf + VD3 was also effective in the prevention of lipid metabolism disorder in diabetic and was able to ameliorate lipid metabolism in non-diabetic rats. These results provide evidence for the potential of Metf and VD3 in the treatment of platelet dysfunction and lipid metabolism impairment in T1D, which may be important in the control and prevention of atherothrombosis in diabetes.

Protective effect of quercetin in ecto-enzymes, cholinesterases, and myeloperoxidase activities in the lymphocytes of rats exposed to cadmium.

The ex vivo and in vitro effects of quercetin on NTPDase, adenosine deaminase (ADA), and acetycholinesterase (AChE) activities in lymphocytes, as well as the effects of quercetin on butyrylcholinesterase (BChE) activity in serum and myeloperoxidase (MPO) activity in plasma were determined in rats. For the ex vivo experiment, animals were orally exposed to Cadmium (Cd) for 45 days. Animals were divided into eight groups: saline/ethanol, saline/Querc 5 mg/kg, saline/Querc 25 mg/kg, saline/Querc 50 mg/kg, Cd/ethanol, Cd/Querc 5 mg/kg, Cd/Querc 25 mg/kg, and Cd/Querc 50 mg/kg. The ex vivo data showed an increase in the ATP and ADP hydrolysis and ADA activity in Cd-exposed rats when compared to the control group. The treatment with quercetin 25 and 50 mg/kg prevented this increase in the ATP and ADP hydrolysis, while the treatment with quercetin 5, 25, and 50 mg/kg prevented the increase in the ADA activity. AChE, BChE, and MPO activities ex vivo presented an increase in the Cd-exposed group when compared to the control group, and the treatment with quercetin 5, 25, and 50 mg/kg prevented this increase caused by Cd exposure. The in vitro experiment showed that quercetin 5, 10, 25, or 50 µM decreased the ADA activity proportionally to the increase of the concentrations of quercetin when compared to the control group. Thus, we can suggest that the quercetin is able to modulate NTPDase, ADA, AChE, and MPO activities and contribute to maintain the levels of ATP, adenosine, and acetylcholine normal, respectively, exhibiting potent pro-inflammatory and anti-inflammatory actions.

Effects of chlorogenic acid, caffeine, and coffee on behavioral and biochemical parameters of diabetic rats.

Diabetes mellitus (DM) is associated with brain alterations that may contribute to cognitive dysfunctions. Chlorogenic acid (CGA) and caffeine (CA), abundant in coffee (CF), are natural compounds that have showed important actions in the brain. The present study aimed to evaluate the effect of CGA, CA, and CF on acetylcholinesterase (AChE), Na(+), K(+)-ATPase, aminolevulinate dehydratase (δ-ALA-D) activities and TBARS levels from cerebral cortex, as well as memory and anxiety in streptozotocin-induced diabetic rats. Animals were divided into eight groups (n = 5-10): control; control/CGA 5 mg/kg; control/CA 15 mg/kg; control/CF 0.5 g/kg; diabetic; diabetic/CGA 5 mg/kg; diabetic/CA 15 mg/kg; and diabetic/CF 0.5 g/kg. Our results demonstrated an increase in AChE activity and TBARS levels in cerebral cortex, while δ-ALA-D and Na(+), K(+)-ATPase activities were decreased in the diabetic rats when compared to control water group. Furthermore, a memory deficit and an increase in anxiety in diabetic rats were observed. The treatment with CGA and CA prevented the increase in AChE activity in diabetic rats when compared to the diabetic water group. CGA, CA, and CF intake partially prevented cerebral δ-ALA-D and Na(+), K(+)-ATPase activity decrease due to diabetes. Moreover, CGA prevented diabetes-induced TBARS production, improved memory, and decreased anxiety. In conclusion, among the compounds studied CGA proved to be a compound which acts better in the prevention of brain disorders promoted by DM.

Hypoxia-ischemia alters nucleotide and nucleoside catabolism and Na+,K+-ATPase activity in the cerebral cortex of newborn rats.

It is well known that the levels of adenosine in the brain increase dramatically during cerebral hypoxic-ischemic (HI) insults. Its levels are tightly regulated by physiological and pathophysiological changes that occur during the injury acute phase. The aim of the present study was to examine the effects of the neonatal HI event on cytosolic and ecto-enzymes of purinergic system--NTPDase, 5'-nucleotidase (5'-NT) and adenosine deaminase (ADA)--in cerebral cortex of rats immediately post insult. Furthermore, the Na(+)/K(+)-ATPase activity, adenosine kinase (ADK) expression and thiobarbituric acid reactive species (TBARS) levels were assessed. Immediately after the HI event the cytosolic NTPDase and 5'-NT activities were increased in the cerebral cortex. In synaptosomes there was an increase in the ecto-ADA activity while the Na(+)/K(+) ATPase activity presented a decrease. The difference between ATP, ADP, AMP and adenosine degradation in synaptosomal and cytosolic fractions could indicate that NTPDase, 5'-NT and ADA were differently affected after insult. Interestingly, no alterations in the ADK expression were observed. Furthermore, the Na(+)/K(+)-ATPase activity was correlated negatively with the cytosolic NTPDase activity and TBARS content. The increased hydrolysis of nucleotides ATP, ADP and AMP in the cytosol could contribute to increased adenosine levels, which could be related to a possible innate neuroprotective mechanism aiming at potentiating the ambient levels of adenosine. Together, these results may help the understanding of the mechanism by which adenosine is produced following neonatal HI injury, therefore highlighting putative therapeutical targets to minimize ischemic injury and enhance recovery.

Ectoenzymes and cholinesterase activity and biomarkers of oxidative stress in patients with lung cancer.

We aimed to examine the nucleoside triphosphate diphosphohydrolases (NTPDase) in lymphocytes; adenosine deaminase (ADA) and butyrylcholinesterase (BChE) in serum; and acetylcholinesterase (AChE), superoxide dismutase (SOD), and catalase (CAT) activity in whole blood; since these enzymes are involved in inflammation responses as well as in oxidative stress conditions. We also checked the levels of total thiols (T-SH), non-protein thiols (NPSH), and thiobarbituric acid reactive substances (TBARS) in serum of patients with lung cancer. We collected blood samples from patients (n = 31) previously treated for lung cancer with chemotherapy. Patients were classified as stage IIIb and IV according to the Union for International Cancer Control (UICC). The results showed a significant increase in the hydrolysis of ATP, ADP, and adenosine in patients when compared with the control group. The activity of AChE, SOD, and CAT as well as the T-SH and NPSH levels were higher in patients group and TBARS levels were lower in patients compared with the control group. These findings demonstrated that the enzymes activity involved in the control of inflammatory and immune processes as well as the oxidative stress parameters are altered in patients with lung cancer.