The progression of the human immunodeficiency virus (HIV) infection to acquired immunodeficiency syndrome (AIDS) can be efficiently interrupted by antiretroviral therapy (ART). However, even successfully treated HIV‐infected individuals are prone to develop non‐AIDS‐related diseases that affect the metabolism and several organs and systems. Biomarkers that predict the occurrence of comorbidities may help develop preventive measures. Current research shows that CD4+ T cell counts and viral load do not predict the development of non‐AIDS‐related diseases. The CD4/CD8 ratio has been indicated as a suitable marker of persistent immune dysfunction and the occurrence of non‐AIDS‐related events in treated HIV‐positive patients. In this study, we explored the relationship between CD4/CD8 ratios, comorbidities, and aging in ART‐treated HIV patients on viral suppression. We collected and evaluated data from 352 HIV‐positive adults who were virologically suppressed (<40 copies/mL) on ART and with CD4 counts above 350 cells/mm3. The median age for participants was 46 years, 218 individuals had at least one comorbidity, and 239 had inverted CD4/CD8 ratios (<1). Current CD4/CD8 ratios were predicted by baseline CD4/CD8 ratios and nadir CD4 counts. Despite the high rates of inverted CD4/CD8 ratios and prevalence of comorbidities, no association between them was observed. The prevalence of comorbidities was significantly higher in older individuals, though aging alone did not explain the rate of all individual comorbidities. Low CD4/CD8 ratios were linked to neurocognitive disorders, suggesting that persistent T cell dysfunction contributes to neurocognitive decline.
Hyperlipidemia generates deposition of lipids, inflammation, and oxidative damage in cells and tissues, including those of the brain. Tucumã (Astrocaryum aculeatum) fruits contain bioactive compounds with antioxidant and anti-inflammatory effects. We evaluated the action of Tucumã extract on memory and brain cortex redox balance in hyperlipidemic rats. For 30 days, Wistar rats received Tucumã extract (250 mg/kg). Then, hyperlipidemia was induced by intraperitoneal administration of Poloxamer-407. Twenty-four hours later, the object recognition index was measured. The animals were euthanized for sample collection 36 hr postinduction.Hyperlipidemic animals showed memory loss and an imbalance between reactive species and intrinsic antioxidants. We found that Tucumã prevented memory loss and protein and lipid oxidative damage and prompted a better antioxidant response in the cerebral cortex of rats with hyperlipidemia. These findings suggest a neuroprotective effect and nutraceutical potential of Tucumã.
Practical applicationsIn the present work, we demonstrated that induced hyperlipidemia in rats caused memory loss and redox unbalance, both factors prevented by the administration of Tucumã (Astrocaryum aculeatum) extract. Two aims were fulfilled with these results.The first was to show that hyperlipidemia affected brain function through oxidative damage and concerned basic research. The second was to offer a therapy that prevented this harm and could be applied in the clinic. Tucumã has ethnopharmacological importance through the consumption of fruits or the administration of extracts and oils by a population that was shown to enjoy improved health and longevity.Here, we show evidence that Tucumã contributes to the maintenance of brain health by preventing memory loss and oxidative damage, a nutraceutical supplement that may aid the prevention of vascular, inflammatory, and brain diseases.
Ectonucleotidases are a plasma membrane‐bound enzyme that hydrolyses extracellular adenosine triphosphate (eATP) and adenosine diphosphate (eADP) to adenosine monophosphate (AMP). It regulates normal function of lymphocytes, acts as an inflammatory marker and represents a molecular target for new therapeutics. Thus, this study sought to isolate lymphocytes from blood (BL), spleen (SL) and cervical lymph node (CLL), and characterize the eATP and eADP enzymatic hydrolysis in Wistar rats. The hydrolysis of the nucleotides occurred primarily at pH 8.0, 37°C in the presence of Ca2+ or Mg2+. Chevillard‐plot showed the hydrolysis of eATP and eADP at the same active site. The inhibitors of some classical ATDPases did not cause any significant change on enzymatic activity. Inhibitors of E‐NTPDase (‐1, ‐2, ‐3 isoforms) and E‐NPP‐1 decrease the enzyme activity in all resident lymphocytes. Furthermore, kinetic parameters (Vmax and Km) revealed that SL had significantly (P < .001) higher enzymatic activity when compared to BL and CLL. In conclusion, this study standardized kinetic values for eATP and eADP hydrolysis for resident lymphocytes isolated from BL, SL and CLL.
Plasma membrane anchored nucleotidases (E-ATPDases), as the E-NTPDase family, could hydrolyse and regulate the pericellular levels of nucleotides in lymphocytes. Each immune organ has a different microenvironment and display lymphocytes with different functions and phenotypes. Considering the different functions of each resident lymphocytes, the E-ATPDases activities in bone marrow (BML), thymus (TL) and mesenteric lymph node (MLL) lymphocytes of Wistar rats were characterized. The hydrolysis of extracellular nucleotides (eATP and eADP) showed linearity in time (0 to 120 min) and protein (1 to 6 μg protein) intervals. The optimal activity was attained at 37ºC in a pH value of 8.0. The essence of cofactor was shown by availability of Ca2+ or Mg2+ within the concentration range of 0 to 1000 µM in the reaction medium, with both ions showing similar effect. The Chevillard plot revealed that the hydrolysis of eATP and eADP occurred at the same active site of the enzyme. The analyses of E-ATPDases inhibitor and enzyme specificity showed possible actions of E-NTPDase isoforms -1 and -2 in the isolated cells. Furthermore, different kinetic behaviour of the nucleotide hydrolysis in each resident lymphocyte was observed in this study, as MLL showed the higher Vmax with the lowest km values, while TL had the lowest Vmax and high km values. The observed variation in enzyme activity of each resident lymphocyte may account for the different physiological signalling of nucleotides in each immune organ.
Objectives
This study was aimed at assessing the anti-arthritic effects of hesperidin on the inflammatory markers in serum/plasma, ectoenzymes activity in platelet, reactive oxygen species (ROS), apoptosis and cell cycle in bone marrow cells of a rat model of arthritis.
Methods
Fifty-six adult female Wistar rats (245–274 g) were grouped into eight of seven rats each: control rats given normal saline or 40 mg/kg of hesperidin or 80 mg/kg of hesperidin, 0.2 mg/kg of dexamethasone, arthritic rats given normal saline, or 40 mg/kg of hesperidin or 80 mg/kg of hesperidin, and 0.2 mg/kg of dexamethasone. Myeloperoxidase and nitrate plus nitrite levels were evaluated in the plasma and serum, respectively. The ecto-nucleoside triphosphate diphosphohydrolases, ecto-5′-nucleotidase and ecto-adenosine deaminase activities were assessed in platelets. Subsequently, the cells of the bone marrow were obtained, and the assays for ROS, apoptosis and cell cycle were evaluated using flow cytometry.
Key findings
The results showed that hesperidin mitigated inflammation, modulated adenosine nucleotides and nucleoside hydrolysing enzymes and levels, minimized ROS intracellularly, attenuated apoptotic process and activated cell cycle arrest in arthritic rat.
Conclusion
This study suggests that hesperidin could be a natural and promising anti-inflammatory compound for the management of arthritis.
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