Amazonian fruits with potential effects on COVID-19 by inflammaging modulation: A narrative review.

The COVID-19 pandemic had a great impact on the mortality of older adults and, chronic non- transmissible diseases (CNTDs) patients, likely previous inflammaging condition that is common in these subjects. It is possible that functional foods could attenuate viral infection conditions such as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causal agent of COVID-19 pandemic. Previous evidence suggested that some fruits consumed by Amazonian Diet from Pre-Colombian times could present relevant proprieties to decrease of COVID-19 complications such as oxidative-cytokine storm. In this narrative review we identified five potential Amazonian fruits: açai berry (Euterpe oleracea), camu-camu (Myrciaria dubia), cocoa (Theobroma cacao), Brazil nuts (Bertholletia excelsa), and guaraná (Paullinia cupana). Data showed that these Amazonian fruits present antioxidant, anti-inflammatory and other immunomodulatory activities that could attenuate the impact of inflammaging states that potentially decrease the evolution of COVID-19 complications. The evidence compiled here supports the complementary experimental and clinical studies exploring these fruits as nutritional supplement during COVID-19 infection. PRACTICAL APPLICATIONS: These fruits, in their natural form, are often limited to their region, or exported to other places in the form of frozen pulp or powder. But there are already some companies producing food supplements in the form of capsules, in the form of oils and even functional foods enriched with these fruits. This practice is common in Brazil and tends to expand to the international market.

Worst spasticity in patients post-stroke associated with MNSOD ALA16VAL polymorphism and interleukin-1ß.

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to risk factors of several metabolic and vascular diseases. However, little is known about interaction between MnSOD Ala16Val SNP in stroke, a frequent neurologic disease that involves clinic manifestations such as motor deficits and spasticity. In this sense, we decided to investigate the relationship between MnSOD Ala16Val SNP with spasticity in stroke and also its influence on interleukin levels, BDNF, and glycolipid parameters. Eighty post-stroke subjects and 80 healthy controls were investigated. We showed a higher spasticity, levels of total cholesterol, LDL, IL-1ß, IL-6, and INF-γ in VV post-stroke group. Interesting, we found a correlation between IL-1ß levels and spasticity in VV post-stroke. Triglycerides, glucose levels and caspases (1 and 3) activation were significantly higher, as well as BDNF levels were lower in VV and AV post-stroke. DNA damage was higher in post-stroke group. Thus, we can suggest that the V allele has a worse glycolipid profile, which would facilitate changes in neurovascular homeostasis. These events associated with an increase in inflammatory markers and a reduction in BDNF can contribute with the stroke and a worse clinical evolution in relation to spasticity in patients with VV genotype.

Açaí (Euterpe oleracea Mart.) reduces the inflammatory response triggered in vitro by the antipsychotic drug olanzapine in RAW 264.7 macrophage cells.

BACKGROUND: Açaí (Euterpe oleracea Mart), a Brazilian fruit, is considered a "superfruit" due its energetic properties and bioactive compounds. The açai's anti-inflammatory effects could attenuate the undesirable metabolic and pro-inflammatory side effects triggered by some antipsychotic drugs, such as Olanzapine (OLZ). It is possible to infer that açai supplement could potentially minimize the adverse effects of OLZ. Aim. This study tested the potential in vitro effects of açai hydroalcoholic extract on the inflammatory activation of the RAW 264.7 macrophage line triggered by OLZ antipsychotic drugs. METHODS: An in vitro protocol was performed using commercial RAW 264.7 macrophages, cultured under sterile conditions at 37°C with 5% CO2 saturation. Initially, a pharmacological curve was defined to determine the concentration of Olanzapine to be used. After this, the cells were supplemented with different concentrations of hydroalcoholic extract of açaí, which had been previously chemically characterized. After 24 and 72 hours of treatment, oxidative and inflammatory tests were performed. Therefore, the aim of this study was to verify whether the hydroalcoholic extract of açaí can modulate the oxy-inflammatory response of olanzapine in vitro. RESULTS: From a preliminary analysis, the açai extract at 5 mg/mL presented higher activity against inflammation triggered by OLZ (0.03 µg/mL). At this concentration, açai was able to reduce several oxidative and inflammatory markers triggered by OLZ (0.03 µg/mL) exposure, such as nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory cytokine levels (IL-1b, IL-6, TNF-a, IFN-g) caused by OLZ (0.03 µg/mL). Moreover, açaí reverted the levels of anti-inflammatory cytokine IL-10 that had been dropped by OLZ exposure to their pre-exposure treatments. CONCLUSIONS: The results suggest that açai extract could be useful in attenuating the peripheral inflammatory states triggered by OLZ. Additional pre-clinical and clinical investigations could be useful in testing therapeutic açai extract supplements.

Safety indicators of a novel multi supplement based on guarana, selenium, and L-carnitine: Evidence from human and red earthworm immune cells.

Neurodegenerative diseases are associated with chronic inflammatory states. There is evidence to support the design of novel supplements based on guarana (G) (Paullinia cupana), selenium (S), and L-carnitine (C), the use of which, potentially attenuates neuro oxi-inflammatory conditions. Therefore, this study analyzed the cytotoxic and redox effects of GSC on human leucocytes, the inflammatory activation of microglia BV-2 cells, and effect on mortality, oxidative metabolism, and the immune modulation of red earthworms (Eisenia fetida). The GSC concentrations tested in cell culture were in the range of 0.04-2.1 mg/mL. All the GSC-supplemented samples tested, reverted H2O2 oxidation in DNA molecules, suggesting its genoprotective potential. GSC did not induce mortality in leucocyte cultures. On the contrary, a reduction in the levels of oxidation of lipids, proteins, and cell apoptosis was observed, via downregulation of caspase 3 and 8 genes. GSC showed a dual effect on microglia, decreasing the cellular proliferation at lower concentrations (<0.24 mg/mL) and increasing the cellular proliferation mainly at concentrations > 1.0 mg/mL. GSC did not have a toxic effect on red earthworms, but induced an increase in amoebocyte cells and in brown body formation, indicating immune response activation. The results suggest that GSC could be safe for human consumption.

Lemongrass (Cymbopogon citratus (D.C.) Stapf) Presents Antitumoral Effect and Improves Chemotherapy Activity in Prostate Cancer Cells.

BACKGROUND: Prostate cancer is the most common visceral neoplasia in men and frequently presents chemotherapy resistance. In this context, lemongrass (Cymbopogon citratus (D.C.) Stapf) has been studied since it presents many important biological activities, such as anticancer. OBJECTIVE: We investigated the antitumor effect of lemongrass and in chemotherapy activity using prostate cancer cells line (DU-145). METHODS: DU-145 cells were exposed to different concentrations of aqueous extract of lemongrass (30; 100; 300; 500 and 1000 µg/mL), isolated and in combination with docetaxel, during 24 and 72 hours. After, cell viability and proliferation, oxidative metabolism, colony formation and cell cycle analyses were performed. Also, we exposed the African green monkey kidney cell line (VERO) to the same lemongrass concentrations to investigate a possible toxicity of this extract. RESULTS: Our findings suggested that lemongrass presented an antitumor effect and improved docetaxel chemotherapy activity by decreasing cell viability and proliferation as well as colony formation. Moreover, we found an oxidative stress increased and cell cycle arresting in G0 /G1 phase. In addition, this extract presented selectivity action for cancer cells, since it did not cause cytotoxicity in normal cells, ensuring non-toxic therapeutic concentrations. CONCLUSION: Lemongrass is a promising medicinal plant that could be used during chemotherapeutic treatment, in order to potentiate the antitumor response and decrease the resistance of prostate cancer.

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.

Astrocaryum aculeatum fruit improves inflammation and redox balance in phytohemagglutinin-stimulated macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Astrocaryum aculeatum G.Mey. (tucumã) is highly consumed by riverside communities in the Amazonian region. These communities have recently been shown to have increased longevity and reduced prevalence of age-related morbidity. Tucumã, which is locally used in their diet and traditional medicine may contribute to these features. AIM OF THE STUDY: To investigate the anti-inflammatory and antioxidant properties of A. aculeatum extract against phytohemagglutinin-induced inflammation in cell cultures. MATERIALS AND METHODS: Cell viability and cytotoxicity assays, gene expression of interleukins IL-1ß, IL-6, IL-10, levels of reactive oxygen species (ROS), nitric oxide (NO) and thiols were employed, as well as the activities of antioxidant enzymes in RAW 264.7 cells stimulated with phytohemagglutinin to mimic inflammation. RESULTS: The extract of A. aculeatum fruit inhibited macrophage proliferation (P < 0.05), arrested the cell cycle in G0/G1 phase (P < 0.001), increased antioxidant defenses (P < 0.01), reduced oxidative stress (P < 0.01), and modulated genes related to the inflammatory response (P < 0.001). CONCLUSION: Our results demonstrate that A. aculeatum fruit has anti-inflammatory and antioxidant capacities. These beneficial effects of tucumã on cells are also likely to be seen in vivo, thereby suggesting that its extract is a suitable therapeutic adjuvant in the prevention or treatment of inflammatory diseases.

Involvement of MnSOD Ala16Val polymorphism in epilepsy: A relationship with seizure type, inflammation, and metabolic syndrome.

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to inflammatory pathways and many metabolic disorders, such as obesity and dyslipidemia. Metabolic syndrome (MetS) is an emergent problem among patients with epilepsy. However, little is known about interaction between MnSOD Ala16Val SNP and metabolic comorbities in epilepsy. Thus, we investigated the relationship between MnSOD Ala16Val SNP with epilepsy and its influence on MetS, inflammation, apoptosis and DNA damage parameters. Ninety subjects were evaluated (47 epilepsy patients and 43 healthy controls) by questionnaires and laboratorial exams. Levels of inflammatory, apoptotic and DNA damage markers, as well as MnSOD polymorphism were assessed. An increased proportion of VV genotype in epilepsy group when compared to control group was observed. Tumor Necrosis Factor-α (TNF-α), Acetylcholinesterase, caspase-8, and Picogreen levels were increased in VV epilepsy group. An important correlation between TNF-α vs caspase-8, and Cholesterol vs. Triglycerides was observed in the epilepsy group with VV genotype. Our findings suggest that the MnSOD Ala16Val SNP might have an important role in epilepsy, mainly in patients with generalized seizures and particularly with VV genotype. The metabolic parameters also presented significant results in epilepsy group with VV genotype, which applying attention in view of further consequences and disorders that could be developed.

Resveratrol-mediated reversal of changes in purinergic signaling and immune response induced by Toxoplasma gondii infection of neural progenitor cells.

The effects of Toxoplasma gondii during embryonic development have not been explored despite the predilection of this parasite for neurons and glial cells. Here, we investigated the activation of the purinergic system and proinflammatory responses during congenital infection by T. gondii. Moreover, neuroprotective and neuromodulatory properties of resveratrol (RSV), a polyphenolic natural compound, were studied in infected neuronal progenitor cells (NPCs). For this study, NPCs were isolated from the telencephalon of infected mouse embryos and subjected to neurosphere culture in the presence of EGF and FGF2. ATP hydrolysis and adenosine deamination by adenosine deaminase activity were altered in conditions of T. gondii infection. P2X7 and adenosine A2A receptor expression rates were augmented in infected NPCs together with an increase of proinflammatory (INF-γ and TNF-α) and anti-inflammatory (IL-10) cytokine gene expression. Our results confirm that RSV counteracted T. gondii-promoted effects on enzymes hydrolyzing extracellular nucleotides and nucleosides and also upregulated P2X7 and A2A receptor expression and activity, modulating INF-γ, TNF-α, and IL-10 cytokine production, which plays an integral role in the immune response against T. gondii.

Analysis of In Vitro Cyto- and Genotoxicity of Barbatimão Extract on Human Keratinocytes and Fibroblasts.

Barbatimão (Stryphnodendron adstringens, Mart.) is a native Brazilian species used in traditional medicine and some commercial preparations owing to its strong wound-healing activity. However, controversy regarding its use due to safety concerns over the potential genotoxic effect of this plant remains. In order to clarify this issue, the effect of hydroalcoholic extract of barbatimão in vitro on cell viability, DNA damage, and induction of apoptosis in two commercial cell lines of keratinocytes (HaCaT) and fibroblasts (HFF-1) was evaluated. Barbatimão stem bark hydroalcoholic extract (70% ethanol) was obtained and lyophilized for subsequent use in all experiments. The main bioactive molecules quantified by HPLC were gallic acid, caffeic acid, quercetin, catechin, and epigallocatechin gallate (EGCG). Barbatimão (0.024 to 1.99 mg/mL) was found to decrease cellular mortality as compared to the control group. GEMO assay, a noncellular DNA protocol that uses H2O2-exposed calf thymus DNA, revealed not only a genotoxic effect of barbatimão, but also a potential genoprotective action against H2O2-triggered DNA fragmentation. These results indicated that barbatimão at concentrations of 0.49 and 0.99 mg/mL, which are near to the levels found in commercial preparations, exerted an in vitro genoprotective effect on cells by decreasing the levels of DNA oxidation quantified by 8-hydroxy-2'-deoxyguanosine (8-OHdG) and reactive oxygen species (ROS) levels. Gene and protein apoptotic markers, quantified by qRT-PCR (BAX/Bcl-2 genes) and immunoassays (Caspases 3 and 8), respectively, also indicated a decrease in apoptotic events in comparison with control cells. Collectively, the results suggest that barbatimão could exert genoprotective and antiapoptotic effects on human keratinocytes and fibroblasts.

High serum uric acid is associated with oxidation of nucleosides in patients with type 2 diabetes.

Uric acid presents different roles in an organism, since it can act as an antioxidant or a pro-oxidant molecule. High serum uric acid levels may cause damage to several structures, including nucleic acids and its components. Therefore, in this study the association between increased serum uric acid concentrations and oxidation of nucleosides was investigated by assessment of urinary 8-hydroxydeoxyguanosine (8-OHdG) in patients with type 2 diabetes (T2D) and in healthy individuals. Urinary 8-OHdG and biochemical parameters were assessed in 61 patients who were initially grouped into 2 groups based on the median serum uric acid levels (<5.3 mg/dL and ≥5.3 mg/dL). Urinary 8-OHdG was higher in patients with T2D and serum uric acid levels ≥5.3 mg/dL, when compared with the patients with serum uric acid levels <5.3 mg/dL; however, co-occurrence of high serum uric acid with high urinary 8-OHdG was not observed in healthy individuals. A significant positive correlation between 8-OHdG and uric acid (r = 0.40, P < 0.01) was observed in patients with T2D. High serum uric acid levels were associated with high urinary 8-OHdG levels in patients with T2D, and this association was independent of gender, hypertension, body mass index, and serum creatinine.

Genetic or pharmacological superoxide-hydrogen peroxide imbalances modulate the in vitro effects of lithium on glycogen synthase kinase-3ß.

INTRODUCTION: Lithium (Li), a mood stabilizer used to treat bipolar disorder (BP) symptoms has important anti-inflammatory effects by downregulation of glycogen synthase kinase-3 beta (GSK-3ß). However, sometime Li effect is not efficient in some patients suggesting genetic interference. Previous investigations described association between a genetic superoxide­hydrogen (S-HP) imbalance caused by a superoxide dismutase manganese dependent gene polymorphism (Val16Ala-SOD2 SNP, rs4880) and differential anti-inflammatory response of some drugs and bioactive molecules. Therefore, we postulated here that S-HP imbalance could present some effect on GSK-3ß modulation by Li. METHODS: to test this hypothesis, a genetic and a pharmacological S-HP imbalance protocols were performed. In the two protocols, immune cells were activated by phythohemaglutin (PHA). The first one, used peripheral blood mononuclear cells (PBMCs) cultures carrying different Val16Ala-SOD2 genotypes, and the second used a commercial macrophage cell line RAW 264.7. Macrophages were exposed to paraquat to induce high S levels (VV-like cells) or porphyrin, that is a SOD2-like molecule that increase dismutation of S into HP (AA-like cells). In both protocols the Li effects on GSK-3ß gene and protein modulation as evaluated in 24 h cultures. The inflammatory activation was also analyzed by cellular proliferation in 72 h cell cultures. RESULTS: as expected PHA exposure triggered a strong upregulation of GSK-3ß gene expression (p ≤ 0.001), and Li exposure showed GSK-3ß gene downregulation from 0.7 mEq/L concentrations. However, Li modulatory effects on GSk-3ß gene and protein expression was directly influenced by basal S-HP balance. Presence of high S-basal levels (VV genotype and VV-like cells) induced attenuated Li anti-inflammatory effects in comparison with balanced and AA and AA-like cells (p < 0.001). Despite methodological limitations related to in vitro assays, the whole of results suggested that Li anti-inflammatory effects is influenced by S-HP basal state and is plausible that its influence could contributes to resistance of some patients to Li treatment or to increase of intensity of some side effects Li-associated.

Association between T102C 5-HT2A receptor gene polymorphism and 5-year mortality risk among Brazilian Amazon riparian elderly population.

OBJECTIVE: Serotonin (5-HT) is a pleiotropic molecule that exerts several functions on brain and peripheral tissues via different receptors. The gene for the 5-HT2A receptor shows some variations, including a T102C polymorphism, that have been associated with increased risk of neuropsychiatric and vascular disorders. However, the potential impact of 5-HT2A imbalance caused by genetic variations on the human lifespan has not yet been established. METHODS: We performed a prospective study involving an Amazon riparian elderly free-living population in Maués City, Brazil, with a 5-year follow-up. Out of a cohort of 637 subjects selected in July, 2009, we genotyped 471 individuals, including 209 males (44.4%) and 262 females (55.6%), all averaging 72.3 ± 7.8 years of age (ranging from 60 to 100 years). RESULTS: The T102C-SNP genotypic frequencies were 14.0% TT, 28.0% CC, and 58.0% CT. From 80 elderly individuals who died during the period investigated, we observed significantly (P = .005) higher numbers of TT carriers (27.3%) and CC carriers (21.2%), compared to heterozygous CT carriers (12.5%). Cox-regression analysis showed that association between the T102C-SNP and elderly survival was independent of age, sex, and other health variables. CONCLUSIONS: Our findings strongly suggest that imbalance in 5-HT2A may cause significant disturbances that lead to an increased susceptibility to death for individuals who are over 60 years of age.

ALA16VAL-MnSOD gene polymorphism and stroke: Association with dyslipidemia and glucose levels.

Stroke risk has been associated to the progression of carotid plaques due to high glucose levels and lipid accumulation, which are greatly associated to cerebral injury, brain oxidative stress, and apoptosis. The ALA16VAL-MnSOD gene single nucleotide polymorphism (SNP) has shown to modulate risk factors of several metabolic and vascular diseases, such as blood glucose (GLU) and lipid levels. However, the association of these factors in stroke patients has not been studied to date. Thus, we evaluated the influence of the Ala16Val-MnSOD SNP on lipid profile, GLU levels, oxidative and DNA damage of 44 patients in a late phase of stroke (>6months). The statistical analysis showed a greater proportion of VV carries in stroke patients. The results also indicated that stroke patients had higher cholesterol (CHO) and GLU levels when compared to healthy counterparts. Interestingly, V allele carriers with stroke showed higher levels of CHO and GLU when compared to AA stroke and healthy counterparts. Our findings suggest that oxidative stress markers are still increased even after 6 months of cerebral injury. Furthermore, we propose that the Ala16Val-MnSOD SNPs may contribute to hypercholesterolemia and higher GLU levels, increasing the risk to neurovascular events that may lead to stroke.

Cytotoxic effects of moderate static magnetic field exposure on human periphery blood mononuclear cells are influenced by Val16Ala-MnSOD gene polymorphism.

Technological advancement has increasingly exposed humans to magnetic fields (MFs). However, more insights are necessary into the potential toxicity of MF exposure as a result of genetic variations related to oxidative metabolism. Therefore, the following study has assessed an in vitro cytotoxic effect of static magnetic field (SMF) (5 mT) on cells with Val16Ala polymorphism (AA, VA, and VV) in the manganese superoxide dismutase gene. Homozygous Val16Ala-superoxide dismutase 2 (SOD2) genotypes present oxidative imbalance that is associated with risk to several chronic degenerative diseases (VV produces less efficient and AA more efficient SOD2 enzyme). Blood samples from healthy adult subject carriers with different Val16Ala-SOD2 genotypes were obtained and exposed to MF at different times (0, 1, 3, 6 h). The cytotoxic effect as well as oxidative stress was evaluated after incubation of 24 h at 37 °C. In addition, apoptosis induction has been analyzed by flow cytometry as well as Bcl-2-associated X protein (BAX), B-cell lymphoma 2 (BCL-2), and caspases 8 and 3 gene expression. SMF cytotoxic effect has been observed in AA cells at all times of exposure, whereas AV cells presented higher mortality only after 6 h of exposure at SMF. Higher apoptosis induction has been observed in AA cells when compared to VV and AV cells. These results suggest a toxicogenetic SMF effect related to an imbalance in SOD2 activity.

Impact of functional determinants on 5.5-year mortality in Amazon riparian elderly.

Objective To ascertain whether modifiable physical performance-based measurements predicted 5.5-year mortality in a riparian elderly cohort in the Amazon rainforest region. Methods A longitudinal study evaluating the impact of functional determinants on 5.5-year mortality in a riparian elderly cohort from Maués City in the state of Amazonas, Brazil, was performed. The study was a follow-up of a previous observational investigation that evaluated various fitness tests in 630 Amazonian riparian elderly (291 males and 339 females) aged 72.3 ± 8.0 (60-99) years old. The cohort was selected for its adverse environmental conditions, which increased the risk of falls yet required maintenance of good physical condition for carrying out relatively rigorous daily activities, and restricted access to specialized health services. Official death records were obtained from the Maués Municipal Health Department. Results A total of 80 study participants (12.7%) died over the 5.5-year study period. Kaplan-Meier regression analysis showed significant association between Timed Up and Go (TUG) test scores ≥ 14 seconds and mortality risk, independent of sex, age, and other health variables. Conclusions The study results suggest that the TUG test can be used as an indicator for initiating therapeutic and preventive actions, including conducting exercises or physical activities adapted to the health and functional conditions of the elderly, by identifying elderly people with a higher relative risk of mortality.

Impact of functional determinants on 5/5-year mortality in Amazon riparian elderly / Influencia de los determinantes de la capacidad funcional sobre la mortalidad a 5/5 años de los ancianos de las zonas ribereñas del Amazonas

ABSTRACT Objective To ascertain whether modifiable physical performance–based measurements predicted 5.5-year mortality in a riparian elderly cohort in the Amazon rainforest region. Methods A longitudinal study evaluating the impact of functional determinants on 5.5-year mortality in a riparian elderly cohort from Maués City in the state of Amazonas, Brazil, was performed. The study was a follow-up of a previous observational investigation that evaluated various fitness tests in 630 Amazonian riparian elderly (291 males and 339 females) aged 72.3 ± 8.0 (60–99) years old. The cohort was selected for its adverse environmental conditions, which increased the risk of falls yet required maintenance of good physical condition for carrying out relatively rigorous daily activities, and restricted access to specialized health services. Official death records were obtained from the Maués Municipal Health Department. Results A total of 80 study participants (12.7%) died over the 5.5-year study period. Kaplan-Meier regression analysis showed significant association between Timed Up and Go (TUG) test scores ≥ 14 seconds and mortality risk, independent of sex, age, and other health variables. Conclusions The study results suggest that the TUG test can be used as an indicator for initiating therapeutic and preventive actions, including conducting exercises or physical activities adapted to the health and functional conditions of the elderly, by identifying elderly people with a higher relative risk of mortality.

RESUMEN Objetivo Evaluar si los parámetros modificables del rendimiento físico permiten predecir la mortalidad a 5,5 años en una cohorte de ancianos de las zonas ribereñas de la selva tropical del Amazonas. Métodos En este estudio longitudinal se evaluó la influencia de los determinantes de la capacidad funcional sobre la mortalidad a 5,5 años en una cohorte de ancianos de la ciudad ribereña de Maués del estado de Amazonas (Brasil). El estudio consistió en un seguimiento de una investigación observacional anterior en la que se efectuaron diversas pruebas para determinar el estado físico de 630 ancianos de las zonas ribereñas del Amazonas (291 hombres y 339 mujeres) de 72,3 años de edad ± 8,0 (60-99) años. La cohorte fue seleccionada en función de las condiciones ambientales adversas, que aumentan el riesgo de caídas pero exigen un buen estado físico para llevar adelante las actividades relativamente rigurosas de la vida cotidiana, así como del acceso limitado a servicios de salud especializados. Los certificados de defunción oficiales se obtuvieron del Ministerio de Salud del Municipio de Maués. Resultados En el transcurso del estudio, que tuvo una duración de 5,5 años, fallecieron 80 participantes (12,7 %). El análisis de regresión de Kaplan-Meier reveló una relación significativa entre los valores de la prueba cronometrada de levantarse y caminar (TUG) ≥ 14 segundos y el riesgo de mortalidad, que fue independiente del sexo, la edad y demás variables de salud. Conclusiones Los resultados de este estudio indican que la prueba TUG puede emplearse como indicador de la necesidad de instituir medidas terapéuticas y preventivas, como ejercicios o actividades físicas adaptadas a la salud y el estado funcional de los ancianos, dado que permite detectar a aquellos que están expuestos a un riesgo relativo de muerte más alto.

Impact of functional determinants on 5.5-year mortality in Amazon riparian elderly / Influencia de los determinantes de la capacidad funcional sobre la mortalidad a 5,5 años de los ancianos de las zonas ribereñas del Amazonas

Objective. To ascertain whether modifiable physical performance–based measurements predicted 5.5-year mortality in a riparian elderly cohort in the Amazon rainforest region. Methods. A longitudinal study evaluating the impact of functional determinants on 5.5-year mortality in a riparian elderly cohort from Maués City in the state of Amazonas, Brazil, was performed. The study was a follow-up of a previous observational investigation that evaluated various fitness tests in 630 Amazonian riparian elderly (291 males and 339 females) aged 72.3 ± 8.0 (60–99) years old. The cohort was selected for its adverse environmental conditions, which increased the risk of falls yet required maintenance of good physical condition for carrying out relatively rigorous daily activities, and restricted access to specialized health services. Official death records were obtained from the Maués Municipal Health Department. Results. A total of 80 study participants (12.7%) died over the 5.5-year study period. Kaplan- Meier regression analysis showed significant association between Timed Up and Go (TUG) test scores ≥ 14 seconds and mortality risk, independent of sex, age, and other health variables. Conclusions. The study results suggest that the TUG test can be used as an indicator for initiating therapeutic and preventive actions, including conducting exercises or physical activities adapted to the health and functional conditions of the elderly, by identifying elderly people with a higher relative risk of mortality.

Objetivo. Evaluar si los parámetros modificables del rendimiento físico permiten predecir la mortalidad a 5,5 años en una cohorte de ancianos de las zonas ribereñas de la selva tropical del Amazonas. Métodos. En este estudio longitudinal se evaluó la influencia de los determinantes de la capacidad funcional sobre la mortalidad a 5,5 años en una cohorte de ancianos de la ciudad ribereña de Maués del estado de Amazonas (Brasil). El estudio consistió en un seguimiento de una investigación observacional anterior en la que se efectuaron diversas pruebas para determinar el estado físico de 630 ancianos de las zonas ribereñas del Amazonas (291 hombres y 339 mujeres) de 72,3 años de edad ± 8,0 (60-99) años. La cohorte fue seleccionada en función de las condiciones ambientales adversas, que aumentan el riesgo de caídas pero exigen un buen estado físico para llevar adelante las actividades relativamente rigurosas de la vida cotidiana, así como del acceso limitado a servicios de salud especializados. Los certificados de defunción oficiales se obtuvieron del Ministerio de Salud del Municipio de Maués. Resultados. En el transcurso del estudio, que tuvo una duración de 5,5 años, fallecieron 80 participantes (12,7 %). El análisis de regresión de Kaplan-Meier reveló una relación significativa entre los valores de la prueba cronometrada de levantarse y caminar (TUG) ≥ 14 segundos y el riesgo de mortalidad, que fue independiente del sexo, la edad y demás variables de salud. Conclusiones. Los resultados de este estudio indican que la prueba TUG puede emplearse como indicador de la necesidad de instituir medidas terapéuticas y preventivas, como ejercicios o actividades físicas adaptadas a la salud y el estado funcional de los ancianos, dado que permite detectar a aquellos que están expuestos a un riesgo relativo de muerte más alto.

Apoptotic markers and DNA damage are related to late phase of stroke: Involvement of dyslipidemia and inflammation.

Oxidative stress and brain inflammation are thought to contribute to the pathophysiology of cerebral injury in acute stroke, leading to apoptosis and cell death. Lipid accumulation may lead to progression of carotid plaques and inflammation, contributing to increased acute stroke risk. However, little is known about these events and markers in the late stroke (>6 months) and if dyslipidemia could contribute to disease's pathophysiology in a later phase. In this case-control study, we recruited patients in the late stroke phase (n=40) and health subjects (control group; n = 40). Dichlorodihydrofluorescein (DCFH), nitrite/nitrate (NOx), Tumor necrosis factor-alpha (TNF-α), Acetylcholinesterase (AChE), Caspase 8 (CASP 8), Caspase 3 (CASP 3) and Picogreen (PG) were measured in periphery blood samples. Furthermore, a correlation among all measured markers (DCFH, NOx, TNF-α, AChE, CASP 8, CASP 3 and PG) was realized. The marker levels were also compared to triglycerides (TG), total (CHO), LDL and HDL cholesterol levels and medications used. Statistical analyses showed that stroke patients presented an increase of DCFH, NOx, TNF-α and AChE levels when compared to control subjects. In addition, we observed that stroke patients had significantly higher CASP 8, CASP 3 and PG levels than control group. A significant correlation between TNF-α with CASP 8 (r = 0.4) and CASP 3 (r = 0.4) levels was observed, but not with oxidative/nitrosative markers. Moreover, we observed that stroke patients with dyslipidemia had significantly higher TNF-α, CASP 8 and CASP 3 levels than stroke without dyslipidemia and control groups. Our findings suggest that oxidative and inflammatory markers may be still increased and lead to caspase activation and DNA damage even after 6 months to cerebral injury. Furthermore, it is plausible to propose that dyslipidemia may contribute to worsen proinflammatory state in a later phase of stroke and an increased risk to new neurovascular events.

Effect of Uncaria tomentosa Extract on Apoptosis Triggered by Oxaliplatin Exposure on HT29 Cells.

Background/Aim. The use of herbal products as a supplement to minimize the effects of chemotherapy for cancer treatment requires further attention with respect to the activity and toxicity of chemotherapy. Uncaria tomentosa extract, which contains oxindole alkaloids, is one of these herbal products. The objective of this study was to evaluate whether Uncaria tomentosa extract modulates apoptosis induced by chemotherapy exposure. Materials and Methods. Colorectal adenocarcinoma cells (HT29 cells) were grown in the presence of oxaliplatin and/or Uncaria tomentosa extract. Results. The hydroalcoholic extract of Uncaria tomentosa enhanced chemotherapy-induced apoptosis, with an increase in the percentage of Annexin positive cells, an increase in caspase activities, and an increase of DNA fragments in culture of the neoplastic cells. Moreover, antioxidant activity may be related to apoptosis. Conclusion. Uncaria tomentosa extract has a role for cancer patients as a complementary therapy. Further studies evaluating these beneficial effects with other chemotherapy drugs are recommended.