Lipotoxicity-associated inflammation is prevented by guarana (Paullinia cupana) in a model of hyperlipidemia.

Hyperlipidemia causes lipotoxicity which prompts an inflammatory response linked to the development of cardiovascular diseases. Natural compounds have been receiving special attention for its potential to treat diseases, inexpensiveness, and safety. Guarana (Paullinia cupana) has demonstrated notable anti-inflammatory and antioxidant effects, which may prevent chronic diseases caused by changes in lipid profile. Thus, this study aims to evaluate the effect of guarana powder (Paullinia cupana) in the purine metabolism and inflammatory profile in lymphocytes and serum of rats with Poloxamer-407-induced hyperlipidemia. Pretreatment with guarana 12.5, 25, and 50 mg/kg/day or caffeine (0.2 mg/kg/day) by gavage was applied to adult male Wistar rats for a period of 30 days. As a comparative standard, we used simvastatin (0.04 mg/kg) post-induction. Hyperlipidemia was acutely induced with intraperitoneally injection of Poloxamer-407 (500 mg/kg). Guarana powder and caffeine increased the activity of the E-NTPDase (ecto-apyrase), and all pretreatments decreased the E-ADA (ecto-adenosine deaminase) activity, reducing the inflammatory process caused by lipotoxicity. In hyperlipidemic rats, ATP levels were increased while adenosine levels were decreased, guarana and caffeine reverted these changes. Guarana powder, caffeine, and simvastatin also prevented the increase in INF-γ and potentiated the increase in IL-4 levels, promoting an anti-inflammatory profile. Guarana promoted a more robust effect than caffeine. Our results show that guarana powder and caffeine have an anti-inflammatory as seen by the shift from a proinflammatory to an anti-inflammatory profile. The effects of guarana were more pronounced, suggesting that guarana powder may be used as a complementary therapy to improve the lipotoxicity-associated inflammation.

Uncaria tomentosa improves cognition, memory and learning in middle-aged rats.

Aging accelerates neurodegeneration, while natural and safe neuroprotective agents, such as Uncaria tomentosa, may help to overcome this problem. This study assessed the effects of U. tomentosa extract treatment on the aging process in the brain of Wistar rats. The spatial memory and learning, acetylcholinesterase (AChE) activity, and DNA damage were assessed. Animals of 14 months were tested with different doses of U. tomentosa (5 mg/kg, 15 mg/kg, and 30 mg/kg) and with different durations of treatment (one month and one year). In the Morris Water Maze (MWM), the escape latency was significantly (p < 0.0001) shorter in rats that received 5 mg/kg, 15 mg/kg, and 30 mg/kg of U. tomentosa for both one month and one year of treatment. There was a significant difference in time spent at the platform zone (p < 0.05) of the middle-aged rats treated with U. tomentosa extract for one year when compared to the control rats. The cortex and hippocampus of rats treated with U. tomentosa for one year showed significant (p > 0.05) reduction in AChE activity. DNA damage index on cortex was significantly lower (p < 0.05) in animals treated with 30 mg/kg of U. tomentosa for one month while all the tested doses demonstrated significant (p < 0.001) reductions in DNA damage index in animals treated for one year. In conclusion, U. tomentosa may represent a source of phytochemicals that could enhance memory activity, repair DNA damage, and alter AChE activity, thereby providing neuroprotection during the aging process.

Antioxidant, hepatoprotective, genoprotective, and cytoprotective effects of quercetin in a murine model of arthritis.

Rheumatoid arthritis is a highly debilitating inflammatory autoimmune disease which is characterized by joint destruction. The present study sought to investigate the effect of quercetin in rats with complete Freund's adjuvant-induced arthritis. Animals were divided into control/saline, control/quercetin (5 mg/kg, 25 mg/kg, and 50 mg/kg) arthritis/saline, and arthritis/quercetin (5 mg/kg, 25 mg/kg, and 50 mg/kg); the treatments were administered for 45 days. Biochemical, oxidative stress, genotoxicity, and cytotoxicity parameters were evaluated. All doses of quercetin reduced the levels of aspartate aminotransferase, thiobarbituric acid-reactive substances, and reactive oxygen species; however, only treatment with 25 or 50 mg/kg increased catalase activity. Total thiol and reduced glutathione levels were not significantly affected by the induction nor by the treatments. Genotoxicity assessed by DNA damage, and cytotoxicity through picogreen assay, decreased after treatments with quercetin. Our results present evidence of the antioxidant, cytoprotective, genoprotective and hepatoprotective, and effects of quercetin, demonstrating its potential as a candidate for coadjuvant therapy.

Increased cytokines production and oxidative stress are related with purinergic signaling and cell survival in post-thyroidectomy hypothyroidism.

Thyroid hormones have essential roles in regulation of cellular functions, including the immune system. The purinergic signaling, activated through extracellular nucleotides and nucleosides has also strong implications in immune response regulation. Hypothyroidism may involve effects on the immune and purinergic systems. In view of that, we evaluated cytokines levels, their relation with the expression of purinergic enzymes and the effects of this condition on immune system cells from patients with post-thyroidectomy hypothyroidism. Increased IL6, IL10, IL17 and TNF-α levels as well as an increase in CD73 expression in lymphocytes were observed in patients' blood. Moreover, augmented myeloperoxidase activity, lipid peroxidation and thiolgroup production were observed in post-thyroidectomy hypothyroidism. In addition, proliferation and cell death of lymphocytes were enhanced when exposed to patients' serum. This study demonstrates that hypothyroidism is related to changes in the purinergic system, increased cytokines production and oxidative stress, which interfere in the cell life and signaling.

Effect of quercetin on E-NTPDase/E-ADA activities and cytokine secretion of complete Freund adjuvant-induced arthritic rats.

The effect of quercetin was assessed in rats induced with complete Freund adjuvant (CFA). Arthritis scores, paw oedema, latency, activities of myeloperoxidase (MPO), ectonucleoside triphosphate diphosphohydrolase (E-NTPDase), and ectoadenosine deaminase (E-ADA) in lymphocytes were determined. Furthermore, nucleotide and nucleoside levels as well as the secretion of pro- and anti-inflammatory cytokines were evaluated. Animals were treated with saline and quercetin in doses of 5, 25, and 50 mg/kg for 45 days. The result revealed that quercetin (50 mg/kg) reduced arthritis score and paw oedema, and increased the latency in the thermal hyperalgesia test. Histopathological analysis showed that all the doses of quercetin reduced infiltration of inflammatory cells. MPO activity was increased in the arthritis group; however, quercetin reduced this activity. E-NTPDase activity was increased in lymphocytes of arthritis rats, and treatment with quercetin reversed this increase. However, E-ADA activity was reduced in the arthritis group, and treatment with quercetin modulated the activity of this enzyme in arthritis rat groups. Serum adenosine levels were increased in arthritis, and the levels were lowered with quercetin treatment. Quercetin treatment in arthritis groups decreased the elevated levels of cytokines in the arthritis control group. Thus, quercetin demonstrated an anti-inflammatory effect, and this flavonoid may be a promising natural compound for the treatment of arthritis. SIGNIFICANCE OF THE STUDY: Quercetin may represent a potential therapeutic compound in the treatment of rheumatoid arthritis. Findings from this study indicate that quercetin suppresses swelling and attenuates the underlying inflammatory responses. This is the first report where quercetin was shown to modulate the immune response to arthritis via attenuation of the purinergic system (E-NTPDase and E-ADA activities) and the levels of IFN-gamma and IL-4. Thus, this work is relevant to basic research and may be translated into clinical practice.

Neuroprotective effects of berberine on recognition memory impairment, oxidative stress, and damage to the purinergic system in rats submitted to intracerebroventricular injection of streptozotocin.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. The present study investigated the effects of 50 and 100 mg/kg berberine (BRB) on recognition memory, oxidative stress, and purinergic neurotransmission, in a model of sporadic dementia of the Alzheimer's type induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) in rats. Rats were submitted to ICV-STZ 3 mg/kg or saline, and 3 days later, were started on a treatment of BRB or saline for 21 days. The results demonstrated that BRB was effective in protecting against memory impairment, increased reactive oxygen species, and the subsequent increase in protein and lipid oxidation in the cerebral cortex and hippocampus, as well as δ-aminolevulinate dehydratase inhibition in the cerebral cortex. Moreover, the decrease in total thiols, and the reduced glutathione and glutathione S-transferase activity in the cerebral cortex and hippocampus of ICV-STZ rats, was prevented by BRB treatment. Besides an antioxidant effect, BRB treatment was capable of preventing decreases in ecto-nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase (EC-5'-Nt), and adenosine deaminase (ADA) activities in synaptosomes of the cerebral cortex and hippocampus. Thus, our data suggest that BRB exerts a neuroprotective effect on recognition memory, as well as on oxidative stress and oxidative stress-related damage, such as dysfunction of the purinergic system. This suggests that BRB may act as a promising multipotent agent for the treatment of AD.

Pretreatment with quercetin prevents changes in lymphocytes E-NTPDase/E-ADA activities and cytokines secretion in hyperlipidemic rats.

Hyperlipidemia (HL) is a condition associated with endothelial dysfunction and inflammatory disorders. Purinergic system ectoenzymes play an important role in modulating the inflammatory and immune response. This study investigated whether the preventive treatment with quercetin is able to prevent changes caused by hyperlipidemia in the purinergic system, through the activities of E-NTPDase and E-ADA in lymphocytes, and quantify the nucleotides and nucleoside, and the secretion of anti- and proinflammatory cytokines. Animals were divided into saline/control, saline/quercetin 5 mg/kg, saline/quercetin 25 mg/kg, saline/quercetin 50 mg/kg, saline/simvastatin (0.04 mg/kg), hyperlipidemia, hyperlipidemia/quercetin 5 mg/kg, hyperlipidemia/quercetin 25 mg/kg, hyperlipidemia/quercetin 50 mg/kg, and hyperlipidemia/simvastatin. Animals were pretreated with quercetin for 30 days and hyperlipidemia was subsequently induced by intraperitoneal administration of 500 mg/kg of poloxamer-407. Simvastatin was administered after the induction of hyperlipidemia. Lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Serum was separated for the cytokines and nucleotide/nucleoside quantification. E-NTPDase and E-ADA activities were increased in lymphocytes from hyperlipidemic rats and pretreatment with quercetin was able to prevent the increase in the activities of these enzymes caused by hyperlipidemia. Hyperlipidemic rats when receiving pretreatment with quercetin and treatment with simvastatin showed decreased levels of ATP and ADP when compared to the untreated hyperlipidemic group. The IFN-γ and IL-4 cytokines were increased in the hyperlipidemic group when compared with control group, and decreased when hyperlipidemic rats received the pretreatment with quercetin. However, pretreatment with quercetin was able to prevent the alterations caused by hyperlipidemia probably by regulating the inflammatory process. We can suggest that the quercetin is a promising compound to be used as an adjuvant in the treatment of hyperlipidemia.

Post-thyroidectomy hypothyroidism increases the expression and activity of ectonucleotidases in platelets: Possible involvement of reactive oxygen species.

Signaling mediated by purines is a widespread mechanism of cell-cell communication related to vasomotor responses and the control of platelet function in the vascular system. However, little is known about the involvement of this signaling as well as the role of reactive oxygen species (ROS) in the development of hypothyroidism. Therefore, the present study investigates changes in the purinergic system, including enzyme activities and expression in platelets, and oxidative profiles in patients with post-thyroidectomy hypothyroidism. The nucleoside triphosphate diphosphohydrolase 1 (NTPDase/CD39) expression in patients increased by 40%, and the adenosine triphosphate (ATP) or adenosine diphosphate (ADP) hydrolyzing activity increased by 82% and 70%, respectively. The activities of ecto-5´-nucleotidase and adenosine deaminase (ADA) also significantly enhanced (39% and 52%, respectively), which correlates with a 45% decrease in adenosine concentration. Furthermore, these patients demonstrated an increased production of ROS (42%), thiobarbituric acid reactive substances (TBARS) (115%), carbonyl protein (30%) and a decreased glutathione S-transferase (GST) activity (20%). This study demonstrates that hypothyroidism interferes with adenine nucleoside and nucleotide hydrolysis and this is correlated with oxidative stress, which might be responsible for the increase in ADA activity. This increase causes rapid adenosine deamination, which can generate a decrease in their concentration in the systemic circulation, which can be associated with the development of vascular complications.

Sepsis induced by cecal ligation and perforation (CLP) alters nucleotidase activities in platelets of rats.

Sepsis is a potentially lethal condition, and it is associated with platelet alterations. The present study sought to investigate the activity of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), E-5'-nucleotidase, and ecto-adenosine deaminase (E-ADA) in the platelets of rats that were induced with sepsis. Male Wistar rats were divided into three groups of ten animals each: a negative control group (normal; NC); a group that underwent surgical procedures (sham); and a group that underwent cecal ligation and perforation (CLP). The induction of sepsis was confirmed by bacteremia, and the causative pathogen identified was Escherichia coli. Hematological parameters showed leukocytosis and thrombocytopenia in animals in the septic group. The results also revealed that there were significant (p < 0.05) increases in adenosine triphosphate (ATP) and adenosine monophosphate (AMP) hydrolyses, and in the deamination of adenosine in the CLP group compared to the sham and control groups. Conversely, ADP hydrolysis was significantly decreased (p < 0.05) in the CLP group compared to the sham and control groups. Purine levels were analyzed by high-performance liquid chromatography (HPLC) in serum samples from control, sham, and CLP groups. Increased concentrations of ATP, adenosine, and inosine were found in the CLP group compared to the sham and control groups. Conversely, the concentrations of ADP and AMP in the CPL group were not significantly altered. We suggest that alterations in hematological parameters, nucleotide hydrolysis in platelets, and nucleotide concentrations in serum samples of rats with induced sepsis may be related to thromboembolic events.

Increased oxidative stress alters nucleosides metabolite levels in sickle cell anemia.

OBJECTIVES: This study was conducted to assess the markers of oxidative stress, myeloperoxidase (MPO), acetylcholinesterase (AChE) and xanthine oxidase (XO) activities as well as the levels of nucleotide metabolites in sickle cell anemia (SCA) patients. METHODS: Fifteen SCA treated patients and 30 health subjects (control group) were selected. The markers of oxidative stress (levels of reactive oxygen species (ROS), plasma proteins, carbonyl content, lipid peroxidation (TBARS), total thiols (T-SH), glutathione and catalase activity), MPO, AChE and XO activities as well as the levels of nucleotide metabolites were measured in SCA patients. RESULTS: ROS, thiobarbituric acid-reactive substances (TBARS) and T-SH levels as well as the activities of catalase and MPO were significantly increased while glutathione level was reduced in SCA patients. Furthermore, a significant (P < 0.001) increase in hypoxanthine level was demonstrated in SCA patients. However, the serum levels for xanthine (P < 0.01) and uric acid (P < 0.001) were decreased in SCA patients. A significant (P < 0.001) decrease in XO activity was detected in SCA patients. DISCUSSION: The altered parameters in SCA patients suggest that the generation and impairment of oxidative stress in this disease as well as antioxidant markers are contributory factors towards cellular redox homeostasis and alteration of purine metabolites.

Curcumin attenuates memory deficits and the impairment of cholinergic and purinergic signaling in rats chronically exposed to cadmium.

This study investigated the protective effect of curcumin on memory loss and on the alteration of acetylcholinesterase and ectonucleotidases activities in rats exposed chronically to cadmium (Cd). Rats received Cd (1 mg/kg) and curcumin (30, 60, or 90 mg/kg) by oral gavage 5 days a week for 3 months. The animals were divided into eight groups: vehicle (saline/oil), saline/curcumin 30 mg/kg, saline/curcumin 60 mg/kg, saline/curcumin 90 mg/kg, Cd/oil, Cd/curcumin 30 mg/kg, Cd/curcumin 60 mg/kg, and Cd/curcumin 90 mg/kg. Curcumin prevented the decrease in the step-down latency induced by Cd. In cerebral cortex synaptosomes, Cd-exposed rats showed an increase in acetylcholinesterase and NTPDase (ATP and ADP as substrates) activities and a decrease in the 5'-nucleotidase activity. Curcumin was not able to prevent the effect of Cd on acetylcholinesterase activity, but it prevented the effects caused by Cd on NTPDase (ATP and ADP as substrate) and 5'-nucleotidase activities. Increased acetylcholinesterase activity was observed in different brain structures, whole blood and lymphocytes of the Cd-treated group. In addition, Cd increased lipid peroxidation in different brain structures. Higher doses of curcumin were more effective in preventing these effects. These findings show that curcumin prevented the Cd-mediated memory impairment, demonstrating that this compound has a neuroprotective role and is capable of modulating acetylcholinesterase, NTPDase, and 5'-nucleotidase activities. Finally, it highlights the possibility of using curcumin as an adjuvant against toxicological conditions involving Cd exposure. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 70-83, 2017.

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.

Guarana (Paullinia cupana) ameliorates memory impairment and modulates acetylcholinesterase activity in Poloxamer-407-induced hyperlipidemia in rat brain.

Hyperlipidemia is a risk factor for the development of cognitive dysfunction and atherosclerosis. Natural compounds have recently received special attention in relation to the treatment of disease due to their low cost and wide margin of safety. Thus, the aim of this study was to determine the possible preventive effect of guarana powder (Paullinia cupana) on memory impairment and acetylcholinesterase (AChE) activity in the brain structures of rats with Poloxamer-407-induced hyperlipidemia. Adult male Wistar rats were pretreated with guarana (12.5, 25 and 50mg/kg/day) and caffeine (0.2mg/kg/day) by gavage for a period of 30days. Simvastatin (0.04mg/kg) was administered as a comparative standard. Acute hyperlipidemia was induced with intraperitoneal injections of 500mg/kg of Poloxamer-407. Memory tests and evaluations of anxiety were performed. The cortex, cerebellum, hippocampus, hypothalamus and striatum were separated to assess acetylcholinesterase activity. Our results revealed that guarana powder was able to reduce the levels of TC and LDL-C in a manner similar to simvastatin. Guarana powder also partially reduced the liver damage caused by hyperlipidemia. Guarana was able to prevent changes in the activity of AChE and improve memory impairment due to hyperlipidemia. Guarana powder may therefore be a source of promising phytochemicals that can be used as adjuvant therapy in the management of hyperlipidemia and cognitive disorders.

Biochemical and oxidative stress markers in the liver and kidneys of rats submitted to different protocols of anabolic steroids.

The objective of this study was to evaluate the effects of different protocols (P1, P2, and P3) of boldenone undecylenate (BU) and stanozolol (ST) on markers of liver and kidney function and variables of oxidative stress in these organs. For this, 54 male Wistar rats were divided into nine groups of six animals each. Each animal received intramuscularly 5.0 mg kg-1 of BU or ST once a week for 4 weeks (P1); 2.5 mg kg-1 of BU or ST once a week for 8 weeks (P2); and 1.25 mg kg-1 of BU or ST once a week for 12 weeks (P3). For each protocol, a control group was used, and they received 0.1 ml of olive oil intramuscularly. Blood and fragments of liver and kidney were collected for alanine aminotransferase activity (ALT), alkaline phosphatase, albumin, creatinine, cholesterol, total protein, triglycerides, urea, reactive oxygen species, thiobarbituric acid reactive substances, total thiols, and glutathione evaluation. The results show that the BU in doses of 5 (day 30) and 2.5 mg kg-1 (day 60) changes the ALT seric activity, possibly showing a hepatotoxic effect. High doses of BU may lead to increased levels of cholesterol (protocol P1) possibly due to inhibition of the normal steroid biosynthesis process. All protocols used caused changes in the redox balance of the organs studied (except in the liver, protocol P2), which indicates that these drugs might be harmful even at low doses.

Berberine protects against memory impairment and anxiogenic-like behavior in rats submitted to sporadic Alzheimer's-like dementia: Involvement of acetylcholinesterase and cell death.

The present study aimed to investigate the effects of berberine (BRB) on spatial and learning memory, anxiety, acetylcholinesterase activity and cell death in an experimental model of intracerebroventricular streptozotocin (ICV-STZ) induced sporadic Alzheimer's-like dementia. Sixty male Wistar rats were randomly divided into six groups: control (CTR), BRB 50mg/kg (BRB 50), BRB 100mg/kg (BRB 100), streptozotocin (STZ), streptozotocin plus BRB 50mg/kg (STZ+BRB 50), and streptozotocin plus BRB 100mg/kg (STZ+BRB 100). Rats were injected with ICV-STZ (3mg/kg) or saline, and daily oral BRB treatment began on day 4 for a period of 21days. Behavioral tests were carried out on day 17, and rats were euthanized on day 24. Cell death analysis and determination of acetylcholinesterase activity was performed on the cerebral cortex and hippocampus of the brain. Administration of BRB prevented the memory loss, anxiogenic behavior, increased acetylcholinesterase activity and cell death induced by ICV-STZ. This may be explained, in part, by a protective effect of BRB on ameliorating the progression of neurodegenerative diseases, including Alzheimer's disease, and the results of this study provide a better understanding of the effect of BRB on the brain. Thus, BRB may act as a potential neuroprotective agent.

Cholinesterases as markers of the inflammatory process associated oxidative stress in cattle infected by Babesia bigemina.

The objective of this study was to assess the influence of an asymptomatic experimental infection by Babesia bigemina on cholinesterase's as markers of the inflammatory process and biomarkers of oxidative imbalance. For this purpose, eight naive animals were used, as follows: four as controls or uninfected; and four infected with an attenuated strain of B. bigemina. Blood samples were collected on days 0, 7 and 11 post-inoculation (PI). Parasitemia was determined by blood smear evaluation, showing that the infection by B. bigemina resulted in mean 0.725 and 0.025% on day 7 and 11 PI, respectively, as well as mild anemia. The activities of acetylcholinesterase, butyrylcholinesterase and catalase were lower, while levels of thiobarbituric acid reactive substances and superoxide dismutase activity were higher in infected animals, when compared with the control group. This attenuated strain of B. bigemina induced an oxidative stress condition, as well as it reduces the cholinesterasés activity in infected and asymptomatic cattle. Therefore, this decrease of cholinesterase in infection by B. bigemina purpose is to inhibit inflammation, for thereby increasing acetylcholine levels, potent anti-inflammatory molecules.

Effect of antiretroviral therapy in thromboregulation through the hydrolysis of adenine nucleotides in platelets of HIV patients.

The human immunodeficiency virus (HIV) infection results in biochemical and vascular dysfunctions. The highly active antiretroviral therapy (HAART) markedly reduces mortality and opportunistic diseases associated with acquired immunodeficiency syndrome (AIDS). This increased survival time predisposes the development of cardiovascular diseases. Platelets present purinergic system ectoenzymes such as E-NTPDase, E-5'-nucleotidase and E-ADA on its surface. In view of this, the aim of this study was to evaluate the activity of these ectoenzymes in platelets as well as the platelet aggregation and lipid profile of patients with HIV infection and also patients receiving HAART. The results showed an increase in the E-NTPDase activity for ATP hydrolysis in the HIV group compared with the control group and the HIV/HAART group. When assessing the activity E-NTPDase hydrolysis to ADP, the results revealed an increase in activity in the HIV group when compared to the control group, and a decrease in activity when in the HIV/HAART group when compared to the control and HIV groups. The activity of E-5'-nucleotidase revealed an increase in AMP hydrolysis in the HIV group, as the results from control and HIV/HAART groups showed no statistical difference. Regarding the E-ADA activity, the HIV and HIV/HAART groups revealed a decreased deamination of adenosine when compared with the control group. Furthermore, we observed an increased platelet aggregation of HIV/HAART group compared with the control group. Thus, our results suggest that antiretroviral treatment against HIV has a significant effect on the activity of purinergic system ectoenzymes demonstrating that thromboregulation is involved in the process.

Epidemiology of Substance Use among University Students in Sudan.

Background. Youth populations are vulnerable to substance use particularly in developing countries where circumstances may be favorable for it. There is no published data on substance use among the youth in Sudan other than on tobacco use. Objectives. The aim of this study was to investigate the prevalence, circumstances, and factors associated with substance use. Methods. An institution-based survey was conducted on a sample of 500 students. Data was collected using a questionnaire designed by the WHO for student drug surveys and analyzed using IBM SPSS version 20. Results. The overall prevalence of substance use is 31%. The current prevalence of tobacco, cannabis, alcohol, amphetamines, tranquilizers, inhalants, opiates, cocaine, and heroin use was 13.7%, 4.9%, 2.7%, 2.4%, 3.2%, 1%, 1.2%, 0.7%, and 0.5%, respectively. Curiosity (33.1%) was the main reason for initiation of substance use. The main adverse effects reported were health problems (19.7%) and theft (19.7%). Peers (40.9%) were the prime source of substance use. On multivariate analysis, male sex was the principle predictor for substance use (AOR: 5.55; 95% CI: 3.38, 9.17). Conclusion. Strategies to control substance use should encompass the role of the university and parents in observing and providing education to improve awareness of substances and their consequences.

Regular exercise training reverses ectonucleotidase alterations and reduces hyperaggregation of platelets in metabolic syndrome patients.

BACKGROUND: Alterations in the activity of ectonucleotidase enzymes have been implicated in cardiovascular diseases, whereas regular exercise training has been shown to prevent these alterations. However, nothing is known about it relating to metabolic syndrome (MetS). We investigated the effect of exercise training on platelet ectonucleotidase enzymes and on the aggregation profile of MetS patients. METHODS: We studied 38 MetS patients who performed regular concurrent exercise training for 30 weeks. Anthropometric measurements, biochemical profiles, hydrolysis of adenine nucleotides in platelets and platelet aggregation were collected from patients before and after the exercise intervention as well as from individuals of the control group. RESULTS: An increase in the hydrolysis of adenine nucleotides (ATP, ADP and AMP) and a decrease in adenosine deamination in the platelets of MetS patients before the exercise intervention were observed (P<0.001). However, these alterations were reversed by exercise training (P<0.001). Additionally, an increase in platelet aggregation was observed in the MetS patients (P<0.001) and the exercise training prevented platelet hyperaggregation in addition to decrease the classic cardiovascular risks. CONCLUSIONS: An alteration of ectonucleotidase enzymes occurs during MetS, whereas regular exercise training had a protective effect on these enzymes and on platelet aggregation.

NTPDase and 5'-nucleotidase activities in synaptosomes of rabbits experimentally infected with BoHV-5.

Bovine herpesvirus type 5 (BoHV-5) is the causative agent of herpetic meningoencephalitis in cattle. The purinergic system is described as a modulator of the immune response and neuroinflammation. These functions are related to the extracellular nucleotides concentration. NTPDase and 5'-nucleotidase are enzymes responsible for controlling the extracellular concentration of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine (ADO). The aim of this study is to determinate the ectonucleotidase activity in cortical synaptosomes and synaptosomes from the hippocampus of rabbits experimentally infected with BoHV-5. Rabbits were divided into four groups, two control groups (non-inoculated animals), and two infected groups (inoculated with BoHV-5). The infected groups received 0.5 ml of BoHV-5 suspension with 10(7.5)TCID50 of viral strain SV-507/99, per paranasal sinuses, and the control groups received 0.5 ml of minimum essential media per paranasal sinuses. Animals were submitted to euthanasia on days 7 and 12 post-inoculation (p.i.); cerebral cortex and hippocampus were collected for the synaptosomes isolation and posterior determination of the ectonucleotidase activities. The results showed a decrease (P < 0.05) in ectonucleotidase activity in synaptosomes from the cerebral cortex of infected rabbits, whereas an increased (P < 0.05) ectonucleotidase activity was observed in synaptosomes from the hippocampus. These differences may be related with the heterogeneous distribution of ectonucleotidases in the different brain regions and also with the viral infectivity. Therefore, it is possible to speculate that BoHV-5 replication results in changes in ectonucleotidase activity in the brain, which may contribute to the neurological signs commonly observed in this disease.