Mechanisms involved in anti-aging effects of guarana (Paullinia cupana) in Caenorhabditis elegans.

Guarana (Paullinia cupana) is habitually ingested by people in the Amazon region and is a key ingredient in various energy drinks consumed worldwide. Extension in longevity and low prevalence of chronic age-related diseases have been associated to habitual intake of guarana. Anti-aging potential of guarana was also demonstrated in Caenorhabditis elegans; however, the mechanisms involved in its effects are not clear. Herein, we investigated the putative pathways that regulate the effects of guarana ethanolic extract (GEE) on lifespan using C. elegans. The major known longevity pathways were analyzed through mutant worms and RT-qPCR assay (DAF-2, DAF-16, SKN-1, SIR-2.1, HSF-1). The possible involvement of purinergic signaling was also investigated. This study demonstrated that GEE acts through antioxidant activity, DAF-16, HSF-1, and SKN-1 pathways, and human adenosine receptor ortholog (ADOR-1) to extend lifespan. GEE also downregulated skn-1, daf-16, sir-2.1 and hsp-16.2 in 9-day-old C. elegans, which might reflect less need to activate these protective genes due to direct antioxidant effects. Our results contribute to the comprehension of guarana effects in vivo, which might be helpful to prevent or treat aging-associated disorders, and also suggest purinergic signaling as a plausible therapeutic target for longevity studies.

Mechanisms involved in anti-aging effects of guarana (Paullinia cupana) in Caenorhabditis elegans

Guarana (Paullinia cupana) is habitually ingested by people in the Amazon region and is a key ingredient in various energy drinks consumed worldwide. Extension in longevity and low prevalence of chronic age-related diseases have been associated to habitual intake of guarana. Anti-aging potential of guarana was also demonstrated in Caenorhabditis elegans; however, the mechanisms involved in its effects are not clear. Herein, we investigated the putative pathways that regulate the effects of guarana ethanolic extract (GEE) on lifespan using C. elegans. The major known longevity pathways were analyzed through mutant worms and RT-qPCR assay (DAF-2, DAF-16, SKN-1, SIR-2.1, HSF-1). The possible involvement of purinergic signaling was also investigated. This study demonstrated that GEE acts through antioxidant activity, DAF-16, HSF-1, and SKN-1 pathways, and human adenosine receptor ortholog (ADOR-1) to extend lifespan. GEE also downregulated skn-1, daf-16, sir-2.1 and hsp-16.2 in 9-day-old C. elegans, which might reflect less need to activate these protective genes due to direct antioxidant effects. Our results contribute to the comprehension of guarana effects in vivo, which might be helpful to prevent or treat aging-associated disorders, and also suggest purinergic signaling as a plausible therapeutic target for longevity studies.

Association between advanced oxidation protein products and 5-year mortality risk among amazon riparian elderly population.

Proteins are important targets of several modifications caused by oxidative stress, leading to structural changes and consequently partial or total loss of their functions. The oxidized proteins include advanced oxidation protein products (AOPP) derived from oxidation-modified albumin, as well as fibrinogen and lipoproteins. An increase in AOPP levels indicates an oxidative stress state and the presence of coexisting inflammation. Several investigations have also suggested an association between high AOPP levels and aging-related diseases. However, the link between elevated AOPP levels and elderly mortality risk has not yet been investigated. Here, we report on a 5-year longitudinal study that investigated the potential association between AOPP levels and mortality using a population-based representative sample of riparian elders living in Brazilian Amazon region (Maués-AM). Age, sex, socioeconomic and cultural conditions, chronic morbidities, polypharmacy, and previous morbidities were also tested as potential confounders. The AOPP levels were measured in 540 (84.78%) individuals, all of whom were followed over a 5-year period in order to establish the mortality rate. Within this study period, 74 (13.7%) elders died and 466 (86.3%) survived. The AOPP levels were higher among the elders who died within the 5-year period (46.27 ± 40.6 mmol/L) compared with those who survived (36.79 ± 20.84 mmol/L) (p = 0.002). The analysis confirmed the link between high AOPP levels and mortality risk, independent of other intervenient factors. These results suggest that elevated AOPP levels could be used to predict mortality risk in elderly patients.

Avaliação da atividade antimicrobiana da planta Tradescantia pallida Munt (Taboquinha Roxa) / Evaluation of antimicrobial activity of the Tradescantia pallida Munt plant (Taboquinha Roxa)

RESUMO O objetivo deste estudo foi pesquisar o efeito antimicrobiano in vitro do extrato hidroalcóolico das folhas Tradescantia pallida Munt conhecida como Taboquinha roxa. Foram realizados testes em meio sólido, onde não observou qualquer halo de inibição, e o método de microdiluição, em que os resultados foram expressivos, com determinação da Concentração Inibitória Mínima (CIM) e Concentração Bactericida Mínima (CBM), com resultados em diferentes concentrações. Foram utilizadas cepas padrão de bactérias Gram positivas e Gram negativas. De acordo com os resultados, sugere-se que essa planta apresenta um potencial antimicrobiano.

ABSTRACT The aim of this study was to investigate the in vitro antimicrobial effect of the hydroalcoholic extract of the Tradescantia pallida Munt leaves,known as Taboquinha roxa. The tests were both conducted on solid mean, where it was not observed any zone of inhibition, and by the micro dilution method, in which the results of the Minimum Inhibitory Concentration (MIC) and the Minimum Bactericidal Concentration (MBC) were significant and related with the different concentrations. Standard strains of bacteria type Gram positive and Gram negative were employed. According to the results, this plant has an antimicrobial potential.

In vitro effects of Ala16Val manganese superoxide dismutase gene polymorphism on human white blood cells exposed to methylmercury.

Environmental contamination by methylmercury (MeHg) is an enormous public health problem in world regions such as Amazonia. MeHg toxic effects seem to be influenced by environmental and genetic factors. However, few studies have evaluated the genetic influences of MeHg toxicity in humans. Therefore, the aim of this study was to evaluate the genetic influence of Ala16Val manganese superoxide dismutase gene polymorphism (Ala16Val-MnSOD) on the cytotoxic effects of in vitro human leukocytes exposed to MeHg. Subjects were selected from 100 individuals aged 26.4 ± 7.3 years genotyped to Ala16Val-MnSOD polymorphism (AA = 6, VV = 6, and AV = 12) to perform in vitro testing using white blood cells (WBCs). Reactive oxygen species production was measured using 2',7'-dichlorofluorescein diacetate fluorimetric assay, and cell viability was measured using MTT assay on WBC samples from the same subjects that were both exposed and not exposed to MeHg (2.5 µM for 6 h). The results showed that AA- and VV-WBCs exposed to MeHg did not display increased reactive oxygen species levels compared to those in cells that were not exposed. However, AV-leukocytes exposed to MeHg displayed increased ROS levels. Cellular viability comparison among genotypes exposed to MeHg showed that the viability of AA-WBCs was lower than that of VV-WBC, with mean values of 3.46 ± 0.13 and 3.08 ± 0.77 (standard error), respectively (P = 0.033), whereas heterozygous cells (AV) displayed intermediate values. This difference was likely due to the higher basal H2O2 production of AA-WBCs compared to that of other genotypes. These results suggest that the Ala16Val-MnSOD polymorphism has toxicogenetic effects in human cells exposed to MeHg.

The protective effects of guaraná extract (Paullinia cupana) on fibroblast NIH-3T3 cells exposed to sodium nitroprusside.

The antioxidant effects of the hydro-alcoholic guaraná extract (Paullinia cupana var. sorbilis Mart.) on nitric oxide (NO) and other compounds generated from the degradation of sodium nitroprusside (SNP) in an embryonic fibroblast culture (NIH-3T3 cells) were evaluated. The guaraná bioactive compounds were initially determined by high-performance liquid chromatography: caffeine=12.240 mg/g, theobromine=6.733 mg/g and total catechins=4.336 mg/g. Cells were exposed to 10 µM SNP during a 6 h period because the cells exhibited >90% mortality at this concentration. Guaraná was added to the cultures in five concentrations (0.5, 1, 5, 10 and 20 mg/mL). The guaraná antioxidant effect was evaluated by viability assays, biochemical oxidation [lipid peroxidation, catalase and superoxide dismutase (SOD) activity] and genotoxicity (DNA Comet assay) analysis. Additionally, oxidative stress was evaluated by a 2,7-dihydrodichlorofluorescein diacetate fluorescence assay. Guaraná reverted the SNP toxicity mainly at lower concentrations (<5 mg), which decreased cell mortality, lipid peroxidation, DNA damage and cell oxidative stress as well as increased the SOD levels. These results demonstrate that guaraná has an antioxidant effect on NO metabolism in situations with higher cellular NO levels.

Hemograma e proteinograma de cutias (Dasyprocta sp. ) hígidas, criadas em cativeiro: influência do sexo e da idade / Haemogram and proteinogram of healthy agouti (Dasyprocta sp. ) raised in captivity: influence of gender and age

Determinaram-se os perfis do hemograma e do proteinograma de 24 cutias (Dasyprocta sp.) saudáveis, criadas em cativeiro, e avaliaram-se a influência de sexo e de idade e a interação sexo-idade. O delineamento foi inteiramente ao acaso em arranjo fatorial 2 x 4 (dois sexos e quatro faixas etárias), com três repetições. Os valores do hemograma e do proteinograma foram: leucócitos totais: 7,24±2,52 (x10³/µl), basófilos: 0,11±0,2 (x10³/µl), eosinófilos: 0,32±0,2 (x10³/µl), segmentados: 2,5±1,22 (x10³/µl), linfócitos: 3,58±1,52 (x10³/µl), monócitos: 0,76±0,47 (x10³/µl), hemácias: 6,51±0,83 (x10(6)/µl), hematócrito: 43,58±3,41 por cento, hemoglobina: 12,71±1,04g/dl, volume corpuscular médio: 67,61±7,52ml, concentração de hemoglobina corpuscular média: 29,19±1,61 por cento, plaquetas: 150,08±63,39 (x10³/ml), proteínas totais: 6,04±1,77g/dl, albumina: 2,07±0,79g/dl e globulinas: 3,97±1,54g/dl. Os parâmetros relativos à série vermelha e ao proteinograma não diferiram quanto ao sexo ou idade, e não houve interação sexo-idade. Os valores de linfócitos foram mais baixos entre os animais mais velhos.

The profiles of hemogram and proteinogram of healthy agouti (Dasyprocta sp.) grown in captivity, in Piauí State, Brazil, were determined, as well as the influence of gender and age factors and the relationship between sex-age them. A completely randomized design was used in a factorial arrange 2x4, two genders and four ages, totaling 24 animals. The mean values of the hemogram were: erythrocytes = 6.51±0.83 (x10(6)); hematocrit = 43.58±3,41 percent; hemoglobin = 12.71±1,04g/dl; mean corpuscular volume = 64.61±7.52μl; mean corpuscular hemoglobin concentration = 29.19±1,61 percent; platelets= 150.08±63.39 (x10³/μl); white blood cells = 7.24±2.52 (x10³/μl); basophils = 0.11±0,2 (x10³/μl); eosinophils = 0,32±0,2 (x10³/μl); neutrophils = 2.5±1,22 (x10³/μl); lymphocytes = 3.58±1.52 (x10³/μl); and monocytes = 0.76±0.47 (x10³/μl). The mean values of the proteinogram were: total serum proteins = 6.04±1.77g/dl; albumin = 2.07±0.79g/dl and globulin = 3.97±1.54g/dl. Neither gender nor age influenced the results of the studied parameters. Association between gender and age was not verified. The values of lymphocytes were lower in older animals.

Níveis iônicos e enzimáticos de cutias (Dasyprocta sp.) hígidas, criadas em cativeiro, influência do sexo e da idade / Ion and enzymatic levels of healthy agouti (Dasyprocta sp.) raised in captivit. Influence of gender and age

Determinou-se o perfil do ionograma e enzimas hepáticas de cutias (Dasyprocta sp.) saudáveis, criadas em cativeiro, como também se avaliou a influência de sexo, idade e interação sexo-idade. Foi adotado um delineamento inteiramente ao acaso, em arranjo fatorial 2 x 4 (dois sexos e quatro faixas etárias), com três repetições, totalizando 24 cutias. Foram determinados os valores para o cálcio (Ca), fósforo (P), cloretos (Cl), aspartato aminotransferase (AST), alanina aminotransferase (ALT), fosfatase alcalina (FA) e gama-glutamiltransferase (GGT). Os valores médios obtidos foram: Ca= 7,62+2,59mg/dl; P= 3,91+1,41mg/dl; Cl= 58,63+16,45mg/dl; AST= 119,54+79,35UI/ml; ALT= 28,08+15,53UI/ml; FA= 26,95+14,01UI/ml e GGT= 25,34+19,44UI/ml. O valor de P foi maior nas fêmeas e da FA nos machos. Os níveis de FA diminuíram com o aumento da idade.

This research studied the profile of the ionogram and hepatic enzymes of healthy agoutis (Dasyprocta sp.) raised in captivity as well as evaluated the influence of gender, age and interaction gender-age. It was used a completely randomized design, in a factorial arrangement of 2 x 4 (two genders and four age groups), with three repetitions, totaling 24 agoutis. The values were determined for calcium (Ca), phosphorus (P), chlorides (Cl), aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT). The mean values were: Ca= 7.62±2.59mg/dl; P= 3.91±1.41mg/dl; Cl= 58.63±16,45mg/dl; AST= 119.54±79.35UI/ml; ALT= 28.08±15.53UI/ml; ALP= 26.95±14.01UI/ml, and GGT= 25.34±19.44UI/ml. The value of P was larger in females and ALP in males. As the age increased, levels of ALP decreased.

Clinical characteristics and outcome of patients with early (<2 h), intermediate (2-4 h) and late (>4 h) presentation treated by primary coronary angioplasty or thrombolytic therapy for acute myocardial infarction.

AIMS: We examined the clinical characteristics and outcome of patients with early (<2 h), intermediate (2-4 h) and late (>4 h) presentation treated by primary angioplasty or thrombolytic therapy for acute myocardial infarction. METHODS AND RESULTS: We studied 2635 patients enrolled in 10 randomized trials of primary angioplasty (n=1302) vs thrombolytic therapy (n=1333) in acute myocardial infarction, and baseline characteristics of the two groups were comparable. Increase in presentation delay is associated with older age, female gender, diabetes and an increased heart rate. We classified the patients according to the time delay from symptom onset to presentation into three categories: early presentation (<2 h), intermediate presentation (2-4 h), and late presentation (>or=4 h). At 30 days the combined rate of death, non-fatal reinfarction and stroke in patients presenting early was 5.8% in the angioplasty group vs 12.5% in the thrombolysis group, in patients with intermediate presentation, 8.6% vs 14.2%, respectively, and in patients presenting late 7.7% vs 19.4%, respectively. With increasing time from symptom onset to presentation, all major adverse cardiac event rates show a trend to a larger increase in the thrombolysis group compared to the angioplasty group, both at 30 days and at 6 months after the acute event. CONCLUSIONS: Major adverse cardiac event rates are lower after angioplasty compared to thrombolysis, irrespective of time to presentation. With increasing time to presentation major adverse cardiac event rates increase after thrombolysis but appear to remain relatively stable after angioplasty.

Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review.

OBJECTIVE: To provide a quantitative review of the treatment effects of primary coronary angioplasty vs intravenous thrombolysis for acute myocardial infarction. DATA SOURCES: Ten randomized trials were identified through computerized bibliographic search of MEDLINE from January 1985 through March 1996 and by queries of principal investigators. STUDY SELECTION: Single-center and multicenter randomized trials comparing primary angioplasty with intravenous thrombolytic therapy among 2606 patients were included. Four trials compared angioplasty with streptokinase, 3 compared angioplasty with a 3- to 4-hour infusion of tissue-type plasminogen activator, and 3 compared angioplasty with "accelerated" administration of tissue-type plasminogen activator over 90 minutes. DATA EXTRACTION: Each investigator provided definitions and exact data for outcome events. Odds ratios (ORs), 95% confidence intervals (CIs), and P values were calculated using exact tests for categorical data. DATA SYNTHESIS: Mortality at 30 days or less was 4.4% for the 1290 patients treated with primary angioplasty compared with 6.5% for the 1316 patients treated with thrombolysis (34% reduction; OR, 0.66; 95% CI, 0.46-0.94; P=.02). The effect was similar among thrombolytic regimens, and no subgroup demonstrated a significant reduction in death. The rates of death or nonfatal reinfarction were 7.2% for angioplasty and 11.9% for thrombolytic therapy (OR, 0.58; 95% CI, 0.44-0.76; P<.001). Angioplasty was associated with a significant reduction in total stroke (0.7% vs 2.0%; P=.007) and hemorrhagic stroke (0.1% vs 1.1%; P<.001). CONCLUSIONS: Based on outcomes at hospital discharge or 30 days, primary angioplasty appears to be superior to thrombolytic therapy for treatment of patients with acute myocardial infarction, with the proviso that success rates for angioplasty are as good as those achieved in these trials. Data evaluating longer-term outcomes, operator experience, and time delay before treatment are needed before primary angioplasty can be universally recommended as the preferred treatment.

Randomized trial of direct coronary angioplasty versus intravenous streptokinase in acute myocardial infarction.

OBJECTIVES: The objective of this study was to obtain preliminary data on the relative clinical utility of direct coronary angioplasty compared with that of intravenous thrombolytic therapy for patients with acute myocardial infarction. BACKGROUND: The relative merits of intravenous thrombolytic therapy and direct coronary angioplasty as treatment for acute myocardial infarction are incompletely understood, and randomized trials of these treatments have been extremely limited. METHODS: One hundred patients with ST segment elevation presenting to a single high volume interventional center within 6 h of the onset of chest pain were randomized to receive either streptokinase (1.2 million U intravenously over 1 h) or immediate catheterization and direct coronary angioplasty. Patients were excluded for age > or = 75 years, prior bypass surgery, Q wave infarction in the region of ischemia or excessive risk of bleeding. All patients were then treated with aspirin (325 mg orally/day) and heparin (1,000 U intravenously/h) for 48 h until catheterization was performed to determine the primary study end point, namely, infarct-related artery patency at 48 h. Secondary end points were in-hospital death, left ventricular ejection fraction at 48 h and time to treatment. RESULTS: There was no difference in the baseline characteristics of the two treatment groups. Overall patient age was 56 +/- 10 years, 83% of patients were male, 11% had prior infarction, 40% had anterior infarction and 97% were in Killip class I or II. Although time to treatment was delayed in the angioplasty group (238 +/- 112 vs. 179 +/- 98 min, p = 0.005), there was no difference in 48-h infarct-related artery patency or left ventricular ejection fraction (patency 74% vs. 80%; ejection fraction 59 +/- 13% vs. 57 +/- 13%; angioplasty vs. streptokinase, p = NS for both). There were no major bleeding events, and the mortality rate with angioplasty (6%) and streptokinase (2%) did not differ (p = NS). CONCLUSIONS: These results suggest that intravenous thrombolytic therapy might be preferred over coronary angioplasty for most patients because of the often shorter time to treatment.

[Detection of myocardial ischemia during dobutamine stress echocardiography. Correlation with coronary cineangiography]. / Detecção de isquemia miocárdica através de ecocardiografia de estresse com dobutamina. Correlação com cinecoronariografia.

PURPOSE: To detect myocardial ischemia during dobutamine stress echocardiography (DSE). METHODS: Two hundred and seventy one patients were studied; 63 (23%) underwent coronary angiography within a month of DSE. Angiograms were analyzed independently by 3 angiographers, and coronary lesions larger than 50% of luminal occlusion were considered likely to cause ischemia. RESULTS: The global sensitivity and specificity were 95% and 75% respectively, with 89% accuracy. Of 43 patients showing obstructive coronary artery disease, there were 2 false negatives. One of 5 false positives had ischemic cardiomyopathy and another a technically difficult exam. The symptoms and side effects in decreasing order of occurrence are as follows: palpitation 46%; arrhythmia 24%; mild hypotension 24%; chest pain 8%; hypertension 5%; facial paresthesia 4%; chills 1.8%; nausea 1.8%; headache 1.4%; dyspnea 0.4% and severe hypotension 0.4%. CONCLUSION: Considering the results, the small number of complications and the feasibility, DSE seems to be a safe and promising method for detecting myocardial ischemia.

Myocardial revascularization without extracorporeal circulation. Seven-year experience in 593 cases.

The authors present the results of 593 consecutive and non-selected patients who underwent direct myocardial revascularization without extracorporeal circulation in the period September 1981 to December 1988. The results are compared with 3086 patients who underwent conventional bypass surgery over the same period of time. The ages varied from 33 to 80 years (mean = 56) with 40 patients older than 70. The overall mortality in the group without cardiopulmonary bypass (CPB) was 1.7% (10/593) compared with 3.8% for conventional revascularization. Our mortality in the last 3 years has been 0.5% and 0% in the last 203 patients revascularized without CPB. The number of grafts varied from 1 to 5 (average 1.6). The treated arteries were: anterior descending (557), right (282) marginal (5) and circumflex marginal (4). Immediate postoperative complications were fewer and hospital discharge was earlier in the group treated without CPB. The authors conclude that this tactical alternative has the advantages of: lower morbidity and mortality, lower cost and no need for blood transfusion. Drawbacks are the need for greater technical expertise and it seems to be possible in about 19% of all patients who undergo myocardial revascularization.

Modified Blalock-Taussig shunt with an umbilical vein graft.

We describe a modification of the Blalock Taussig anastomosis, with the interposition of a glutaraldehyde-tanned umbilical vein graft between the subclavian and pulmonary arteries. This operation was performed in 64 children: 11 were less than 1 month of age (17.2%), and 23 were between 1 and 6 months of age (34.9%). Hospital deaths occurred in six patients-all less than 6 months of age (9.4%). There was no instance of shunt occlusion noted. The clinical course was uneventful among survivors, except for one patient who died of endocarditis in the late postoperative follow-up. The shunt procedure may be performed very rapidly, with minimal dissection, allowing the use of a graft larger than the diameter of the subclavian artery. This modification of the Blalock Taussig operation compares favorably with our previous experience with other shunt procedures and may be considered a valuable alternative in the palliative surgical treatment of several malformations with severe pulmonary oligemia.

Revascularizacao miocardica pela anastomose mamario-coronaria. Analise critica dos resultados imediatos e tardios. / Myocardial revascularization through mammary-coronary anastomosis. Critical analysis of immediate and late results

Os autores estudam um grupo de 75 pacientes, consecutivos e nao selecionados, submetidos a revascularizacao miocardica, nos quais a anastomose mamario-coronaria foi utilizada como procedimento isolado ou associado a pontes de safena. Nesses pacientes a idade variou de 38 a 72 anos predominando o sexo masculino (82%). Em 43 pacientes (57,3%) associou-se uma ou mais pontes de safena e em dois aneurismectomia do VE. A mortalidade hospitalar foi de 5 casos (6,7%) nao se observando morbidade especial decorrente deste tipo de procedimento. Considerou-se como fatores de sucesso a sobrevida e a ausencia de sintomatologia anginosa que na analise atuarial, foram obtidos em 90,8% e 80,4% em 5 anos, respectivamente. As vantagens e desvantagens da utilizacao desse tipo de enxerto sao analisadas, bem como suas limitacoes. Em vista dos resultados obtidos os autores consideram a anastomose mamario-coronaria, quando adequadamente indicada, a melhor opcao na revascularizacao do territorio da arteria descendente anterior e seus ramos diagonais