Unravelling the Gastroprotective Potential of Kefir: Exploring Antioxidant Effects in Preventing Gastric Ulcers.

The present study was conducted to evaluate the protective effect of milk kefir against NSAID-induced gastric ulcers. Male Swiss mice were divided into three groups: control (Vehicle; UHT milk at a dose of 0.3 mL/100 g), proton pump inhibitor (PPI; lansoprazole 30 mg/kg), and 4% milk kefir (Kefir; 0.3 mL/100 g). After 14 days of treatment, gastric ulcer was induced by oral administration of indomethacin (40 mg/kg). Reactive oxygen species (ROS), nitric oxide (NO), DNA content, cellular apoptosis, IL-10 and TNF-α levels, and myeloperoxidase (MPO) enzyme activity were determined. The interaction networks between NADPH oxidase 2 and kefir peptides 1-35 were determined using the Residue Interaction Network Generator (RING) webserver. Pretreatment with kefir for 14 days prevented gastric lesions. In addition, kefir administration reduced ROS production, DNA fragmentation, apoptosis, and TNF-α systemic levels. Simultaneously, kefir increased NO bioavailability in gastric cells and IL-10 systemic levels. A total of 35 kefir peptides showed affinity with NADPH oxidase 2. These findings suggest that the gastroprotective effect of kefir is due to its antioxidant and anti-inflammatory properties. Kefir could be a promising natural therapy for gastric ulcers, opening new perspectives for future research.

Aplicações terapêuticas do Cymbopogon citratus (capim-limão) na odontologia: uma revisão de literatura integrativa / Therapeutic applications of Cymbopogon citratus (lemon grass) in dentistry: an integrative literature review

Introdução: O Cymbopogon citratus (capim-limão) é uma espécie herbácea pertencente à família Poaceae, que engloba aproximadamente 500 gêneros e 8.000 espécies. Objetivos: Analisar as evidências científicas disponíveis sobre as aplicações terapêuticas de Cymbopogon citratus (capim-limão) na Odontologia durante os últimos dez anos. Métodos: Trata-se de uma revisão integrativa da literatura, que envolveu as seguintes etapas: elaboração da pergunta norteadora, estabelecimento das palavras-chave e dos critérios de inclusão e exclusão de artigos, seleção e análise crítica dos artigos, resultados, discussão e conclusão. Resultados: 8% dos artigos encontrados e analisados nessa revisão de literatura integrativa demonstraram que o Cymbopogon citratus (capim-limão) apresenta potencial terapêutico no que se refere a suas propriedades antimicrobianas, sendo considerado benéfico e promissor na inibição de patógenos colonizadores bacterianos e fúngicos dentários, além de demonstrar baixa citotoxicidade. Conclusão: Apesar da existência de diversas pesquisas in vitro que demonstram eficácia e segurança do uso de diversos compostos de origem natural, nota-se que há poucos protocolos específicos que orientem o profissional cirurgião-dentista para o uso de terapias à base de plantas medicinais e/ou fitoterápicos, como no caso do Cymbopogon citratus (capim-limão). Portanto, são necessários mais estudos para explicar e fundamentar melhor os efeitos do capim-limão na odontologia.

Introduction: Cymbopogon citratus (lemon grass) is an herbaceous species belonging to the Poaceae family, which includes approximately 500 genera and 8,000 species. Objectives: To analyze the available scientific evidence about therapeutic applications of Cymbopogon citratus (lemon grass) in Dentistry over the past ten years. Methods: This is an integrative literature review, which involved the following steps: elaboration of the guiding question, establishment of keywords and criteria for inclusion and exclusion of articles, selection and critical analysis of articles, results, discussion, and conclusion. Results: 8% of the articles found and analyzed in this integrative literature review demonstrated that Cymbopogon citratus (lemon grass) has therapeutic potential because its antimicrobial properties, being considered beneficial and promising in the inhibition of bacterial and fungal dental colonizing pathogens, in addition presents low cytotoxicity. Conclusion: Despite the existence of several in vitro studies that demonstrate the efficacy and safety of natural compounds utilization, there are few specific protocols guiding the dental professional about using based therapies of medicinal and/or phytotherapeutic plants, as in the case of Cymbopogon citratus (lemon grass). Therefore, more studies are necessary to explain and provide a better validation of lemon grass effects in the dentistry practice.

Use of kefir peptide (Kef-1) as an emerging approach for the treatment of oxidative stress and inflammation in 2K1C mice.

The benefits of kefir consumption are partially due to the rich composition of bioactive molecules released from its fermentation. Angiotensin-converting enzyme (ACE) inhibitors are bioactive molecules with potential use in the treatment or prevention of hypertension, heart failure, and myocardial infarction. Here, the in vivo actions of the Kef-1 peptide, an ACE inhibitor derived from kefir, were evaluated in an angiotensin II-dependent hypertension model. The Kef-1 peptide showed a potential anti-hypertensive effect. Additionally, Kef-1 exhibited systemic antioxidant and anti-inflammatory activities. In smooth muscle cells (SMCs), the Kef-1 peptide decreased ROS production through the reduced participation of NADPH oxidase and mitochondria. The aorta of 2K1C mice treated with Kef-1 showed lesser wall-thickening and partial restoration of the endothelial structure. In conclusion, these novel findings highlight the in vivo biological potential of this peptide demonstrating that Kef-1 may be a relevant nutraceutical treatment for cardiovascular diseases.

Oxidative Stress and Dementia in Alzheimer's Patients: Effects of Synbiotic Supplementation.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia in elderly patients. Recently, several studies have shown that inflammation and oxidative stress precede the cardinal neuropathological manifestations of AD. In view of the proven antioxidant effects of probiotics, we proposed that continuous dietary supplementation with milk fermented with kefir grains might improve cognitive and metabolic and/or cellular disorders in the AD patients. METHODS: This study was designed as an uncontrolled clinical investigation to test the effects of probiotic-fermented milk supplementation (2 mL/kg/daily) for 90 days in AD patients exhibiting cognitive deficit. Cognitive assessment, cytokine expression, systemic oxidative stress levels, and blood cell damage biomarkers were evaluated before (T0) and after (T90) kefir synbiotic supplementation. RESULTS: When the patients were challenged to solve 8 classical tests, the majority exhibit a marked improvement in memory, visual-spatial/abstraction abilities, and executive/language functions. At the end of the treatment, the cytometric analysis showed an absolute/relative decrease in several cytokine markers of inflammation and oxidative stress markers (·O2 -, H2O2, and ONOO-, ~30%) accompanied by an increase in NO bioavailability (100%). In agreement with the above findings by using the same technique, we observed in a similar magnitude an improvement of serum protein oxidation, mitochondrial dysfunction, DNA damage/repair, and apoptosis. CONCLUSION: In conclusion, we demonstrated that kefir improves cognitive deficits, which seems to be linked with three important factors of the AD-systemic inflammation, oxidative stress, and blood cell damage-and may be a promising adjuvant therapy against the AD progression.

Physiological and Biochemical Vascular Reactivity Parameters of Angiotensin II and the Action of Biased Agonist TRV023.

Vascular reactivity experiments using isolated aortic rings have been widely used as a model for physiological and pharmacological studies since the early sixties. Here, we suggest several parameters that the researcher should pay attention to when investigating angiotensin II in their experimental models. Angiotensin II is one of the active peptides of the renin-angiotensin system and exerts its effect through the AT1 and AT2 receptors. Some studies seek to understand the effects of angiotensin II receptors at the vascular level by using vascular reactivity experiments. However, because of the large number of variations, there are only a handful of reactivity studies that seek to use this method. Thus, the objective of this study was to standardize experimental methods with angiotensin II, through vascular reactivity protocols. For this, variables such as basal tension, concentration interval, single concentration, curve concentration response, and multiple experiments using the same aortic ring were developed using the technique of vascular reactivity in an organ bath. This is the first study that has standardized the vascular reactivity protocol. In addition, we demonstrated the effects of TRV023-biased ligand of the AT1R at vascular sites.

Worsening of Oxidative Stress, DNA Damage, and Atherosclerotic Lesions in Aged LDLr-/- Mice after Consumption of Guarana Soft Drinks.

BACKGROUND: Excessive consumption of soft drinks (SD) has become a health problem worldwide due to its association with related cardiovascular diseases. We investigated the possible impacts associated with the consumption of Brazilian guarana (normal and zero) SD in dyslipidemic mice, thus mitigating potential clinical confounders such as poor-quality diet, lifestyle, body composition, and/or comorbidities. METHODS: Sixteen-month-old LDLr-/- mice were divided into the following groups: (1) control; (2) GSD: normal guarana SD; and (3) Z-GSD: zero guarana SD. All were fed ad libitum, and blood pressure was measured noninvasively. After 8 weeks, aorta, blood, liver, and stomach samples were collected for histological and biochemical analyses. RESULTS: Guarana soft drinks increased atherosclerosis (~60%) and were associated with hypercholesterolemia, hypertension, oxidative stress, DNA fragmentation, and apoptosis (~2-fold) of blood cells, besides presenting an increase in liver and gastric damage even in normoglycemia. Interestingly, Z-GSD did not cause the aforementioned changes, except in hemodynamic and renal parameters. CONCLUSIONS: Chronic administration of GSD is prooxidative, compromising the cardiovascular, gastric, and hepatic systems; the effects are due at least in part to free sugar consumption but not to guarana extract per se.

Chronic iron overload intensifies atherosclerosis in apolipoprotein E deficient mice: Role of oxidative stress and endothelial dysfunction.

AIMS: We previously demonstrated that iron overload induces endothelial dysfunction and oxidative stress, which could increase the risk for atherosclerosis. However, the iron-related harmfulness under a genetic predisposition to atherosclerosis is still unclear. Here, we have tested the hypothesis that chronic iron overload may change vascular reactivity associated with worsening of the atherosclerotic process in apolipoprotein E knockout (apoE(-/-)) mice. MAIN METHODS: Serum and aortas of wild-type (WT) and apoE(-/-) mice injected with iron-dextran (IO, 10 mg/mouse/day, ip) or saline 5 times a week for 4 weeks, were used. KEY FINDINGS: Iron overload increased serum levels of iron and biomarkers of liver injury and oxidative stress, and iron deposition in the aorta in both lines, but only apoE(-/-) IO mice had intensified hypercholesterolemia and atherosclerosis. By scanning electron microscopy, the small endothelial structural damage caused by iron in WT was worsened in the apoE(-/-) group. However, endothelial dysfunction was found only in the apoE(-/-) IO group, identified by impaired relaxation to acetylcholine and hyperreactivity to phenylephrine associated with reduced nitric oxide modulation. Moreover, tiron and indomethacin attenuated reactivity to phenylephrine with greater magnitude in aortas of the apoE(-/-) IO group. Confirming, there were changes in the antioxidant (superoxide dismutase and catalase) activity, increased expression of cyclooxygenase-2 in the aorta and elevated levels of thromboxane A2 and prostacyclin metabolites in the urine of apoE(-/-) IO. SIGNIFICANCE: Our results showed that chronic iron overload intensifies the atherosclerotic process and induces endothelial dysfunction in atherosclerotic mice, probably due to the oxidative stress and the imbalance between the relaxing and contractile factors synthesized by the damaged endothelium.

Silymarin protects against radiocontrast-induced nephropathy in mice.

Silymarin, an extract from Silybum marianum (milk thistle) containing a standardized mixture of flavonolignans that ameliorates some types of liver disease and, more recently, kidney damage, could be used for the ROS-scavenging effect of these antioxidants. Furthermore, contrast-induced nephropathy (CIN) is an iatrogenic impairment of renal function in patients subjected to angiographic procedures for which there is not yet a successful preventative treatment. Recent evidence has shown that this event is related to tubular/vascular injury activated mainly by oxidative stress. However, whether this bioavailable and pharmacologically safe extract protects against CIN is not clear. We proposed to evaluate the possible protective role of the antioxidant silymarin in an experimental model of CIN. Adult male Swiss mice were separated into 6 groups and pretreated orally with silymarin (50, 200 and 300 mg/kg), N-acetylcysteine (200 mg/kg) or vehicle for 5 days before the CIN and control groups. Renal function was analyzed by plasma creatinine, urea and cystatin C levels. Additionally, blood reactive oxygen species (ROS) were evaluated using ROS bioavailability, protein oxidation and DNA damage. Renal oxidative damage was evaluated using apoptosis/cell viability assays and histological analysis. We showed that silymarin preserved renal function and decreased systemic and renal oxidative damage (antigenotoxic and antiapoptotic properties, respectively) in a dose-dependent manner and was superior to conventional treatment with N-acetylcysteine. Histologically, silymarin treatment also had beneficial effects on renal glomerular and tubular injuries. Therefore, silymarin prophylaxis may be an interesting strategy for the prevention of CIN.

Lipectomy associated to obesity produces greater fat accumulation in the visceral white adipose tissue of female compared to male rats.

BACKGROUND: Mobility of fat deposited in adipocytes among different fatty territories can play a crucial role in the pathogenesis of obesity-related diseases. Our goal was to investigate which of the remaining fat pads assume the role of accumulating lipids after surgical removal of parietal WAT (lipectomy; LIPEC) in rats of both sexes displaying MSG-induced obesity. METHODS: The animals entered the study straight after birth, being separated according to gender and randomly divided into CON (control, saline-treated) and MSG (monosodium glutamate-treated) groups. Next, the animals underwent LIPEC or sham-operated surgery (SHAM). Obesity was induced by the injection of MSG (4 mg/g/day) during neonatal stage (2nd to 11th day from birth). LIPEC was performed on the 12th week, consisting in the withdrawal of parietal WAT. On the 16th week, the following WATs were isolated and collected: peri-epididymal-WAT (EP-WAT); parametrial-WAT (PM-WAT); omental-WAT (OM-WAT); perirenal-WAT (PR-WAT) and retroperitoneal-WAT (RP-WAT). RESULTS: The adiposity index was significantly increased in both male (3.2 ± 0.2** vs 1.8 ± 0.1) and female (4.9 ± 0.7* vs 2.6 ± 0.3) obese rats compared to their respective control groups. LIPEC in obese animals produced fat accumulation in visceral fat sites in a more accentuated manner in female (3.6 ± 0.3** vs 2.8 ± 0.3 g/100 g) rather than in male (1.8 ± 0.2* vs 1.5 ± 0.1 g/100 g) rats compared to obese non-lipectomized animals. Among the visceral WATs, the greater differences were observed between gonadal WATs of obese lipectomized rats, with higher accumulation having been observed in PM-WAT (2.8 ± 0.3* vs 2.1 ± 0.2 g/100 g) rather than in EP-WAT (1.0 ± 0.1 ± 0.9 ± 0.1 g/100 g) when compared to obese non-lipectomized animals. CONCLUSIONS: The results of the present study led us to conclude that obesity induced by MSG treatment occurs differently in male and female rats. When associated with parietal LIPEC, there was a significant increase in the deposition of visceral fat, which was significantly higher in obese female rats than in males, indicating that fat mobility among WATs in lipectomized-obese rats can occur more expressively in particular sites of remaining WATs.

Identification of new bioactive peptides from Kefir milk through proteopeptidomics: Bioprospection of antihypertensive molecules.

Kefir, a probiotic beverage prepared from fermented milk, has been associated with antihypertensive activity. However, the bioactive molecules responsible for this activity still remain unclear. Therefore, in this study we aim to evaluate the mechanisms of the antihypertensive effects of Kefir in the two-kidney one-clip hypertension model, and to bioprospect for bioactive peptides identified by proteomic methodologies. Treatment with Kefir was performed via gavage, and resulted in a 37 mmHg reduction in systolic arterial pressure and 19% inhibition of angiotensin converting enzyme (ACE) activity. For the proteopeptidomic study, the protein extract of Kefir beverage and non-fermented bovine milk were analysed by MALDI-TOF mass spectrometry, and their tryptic digestion products sequenced via Shotgun proteomics (Q-Exactive mass spectrometer). A list of 35 peptides with potential hypertensive activity due to ACE inhibition were identified. These results demonstrate the benefits of Kefir products, and may guide the design of new antihypertensive drugs.

Gastroprotective effect of oral kefir on indomethacin-induced acute gastric lesions in mice: Impact on oxidative stress.

AIMS: This study investigated the gastroprotective effects and the systemic oxidative status of oral kefir pretreatment in albino mice submitted to acute gastric ulcer induced by indomethacin. MAIN METHODS: Male Swiss mice were divided into three groups (n = 7): Vehicle (0.3 mL of whole milk/100 g body weight, pH adjusted to 5.0), Kefir (0.3 mL of kefir/100 g body weight) and Proton Pump Inhibitor (PPI, 30 mg/kg of lansoprazole), via gavage for 14 days. Animals were fasted for 16 h and treated orally with indomethacin (40 mg/kg). After 6 h the animals were euthanized, the blood samples were obtained and used for the determination of ROS production, oxidation of macromolecules and apoptosis. The stomachs were removed, opened by the greater curvature, and a macroscopic analysis of the gastric lesions was performed. KEY FINDINGS: Our findings demonstrated that the symbiotic kefir significantly alleviated blood oxidative stress by reducing superoxide anion, hydrogen peroxide and hydroxyl/peroxynitrite radicals, thereby leading to reduced oxidative damage to macromolecules due to a decreased oxidative stress status in induced gastric lesions. These anti-oxidative properties might contribute favorably to the ulcer attenuation in the kefir group. SIGNIFICANCE: Taken together, these findings support a significant role played by the antioxidant actions of kefir in counteracting the gastric damage induced by this cyclooxygenase inhibitor. It is also worthy to mention that, kefir also exerted the gastroprotective property partly by inhibiting oxidative systemic damage. Based on these considerations, it was implied that kefir might be a contributor for the ROS-scavenging effect.

The benefits of soluble non-bacterial fraction of kefir on blood pressure and cardiac hypertrophy in hypertensive rats are mediated by an increase in baroreflex sensitivity and decrease in angiotensin-converting enzyme activity.

OBJECTIVES: We aimed to evaluate whether long-term treatment with the soluble non-bacterial fraction of kefir affects mean arterial pressure (MAP) and cardiac hypertrophy through the modulation of baroreflex sensitivity, ACE activity, and the inflammatory-to-anti-inflammatory cytokine ratio in spontaneously hypertensive rats (SHRs). METHODS: SHRs were treated with the soluble non-bacterial kefir fraction (SHR-kefir) or with kefir vehicle (SHR-soluble fraction of milk). Normotensive control Wistar Kyoto animals received the soluble fraction of milk. All treatments were administered by gavage (0.3 mL/100g/body weight), once daily for eight weeks. At the end, after basal MAP and Heart Rate (HT) measurement, barorreflex sensitivity was evaluated through in bolus administrations of sodium nitroprusside and phenylephrine (AP50 [arterial pressure 50%], the lower plateau, and HR range were measured). ACE activity and cytokines (TNF-α and IL-10) were evaluated by ELISA. Cardiac hypertrophy was analysed morphometrically. RESULTS: Compared to SHR control, SHR-kefir exhibited a significant decrease in both MAP (SHR: 184 ± 5; SHR-Kefir: 142 ± 8 mmHg), and HR (SHR: 360 ± 10; SHR-kefir: 310 ± 14 bpm). The non-bacterial fraction of kefir also reduced cardiac hypertrophy, TNF-α-to-IL10 ratio, and ACE activity in SHRs. SHR-kefir baroreflex sensitivity, resulted in a partial but significant recovery of baroreflex gain, as demonstrated by improvements in AP50, the lower plateau, and HR range. CONCLUSION: In summary, our results indicate that long-term administration of the non-bacterial fraction of kefir promotes a significant decrease in both MAP and HR, by improving baroreflex, and reduces cardiac hypertrophy in SHRs, likely via ACE inhibition, and reduction of the TNF-α-to-IL10 ratio.

Chronic administration of antioxidant resin from Virola oleifera attenuates atherogenesis in LDLr -/- mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Virola oleifera (Schott) A. C. Smith, Myristicaceae has been largely used in traditional folk medicine in Brazil as an anti-inflammatory agent and our previous data indicated the antioxidant properties in other oxidative stress-related models. However, its effects on atherosclerosis (AT) are not yet investigated. AIMS OF THE STUDY: To evaluate the influence of resin from Virola oleifera (RV) on progression of AT in LDLr-/- mice. MATERIALS AND METHODS: LDLr-/- mice were divided into 4 groups: 1) The ND group received a normal diet without treatment. 2) The HD group received a high-fat diet without treatment. 3) The HD-V50 received a high-fat diet and was orally treated with RV at 50mg/Kg. 4) The HD-V300 received a high-fat diet and was orally treated with RV at 300mg/Kg. After 4 weeks, blood was collected to quantify biochemical parameters and ROS total and the aorta was removed to measure the lipid deposition by en face analysis. The liver was also collected to determine total lipids and lipid and protein oxidation. In order to investigate in more detail the contributions of RV in the vascular structure, we carried out the in vitro tests using four cellular types: macrophages, fibroblasts, vascular smooth muscle and endothelial cells. RESULTS: We showed that the chronic treatment of RV at both doses reduced vascular lipid accumulation (~50%, p<0.05), probably through systemic and hepatic antioxidant effects, independent of dyslipidemia. Moreover, the in vitro assay results demonstrated that RV develops antioxidant properties on the vascular smooth muscle and endothelial cells, reinforcing the protective role of RV in progression of AT. LPS-stimulated macrophages treated with RV resulted in a significant reduction of NO production in a concentration-dependent manner. CONCLUSIONS: Chronic treatment with RV diminishes lipid deposition in atherosclerotic mice, which may be justified, at least in part, by antioxidant systemic and local mechanisms, reinforcing the protective role this resin in the setting of vascular lipid deposition, independent of hypercholesterolemia.

Coadjuvants in the Diabetic Complications: Nutraceuticals and Drugs with Pleiotropic Effects.

Because diabetes mellitus (DM) is a multifactorial metabolic disease, its prevention and treatment has been a constant challenge for basic and clinical investigators focused on translating their discoveries into clinical treatment of this complex disorder. In this review, we highlight recent experimental and clinical evidences of potential coadjuvants in the management of DM, such as polyphenols (quercetin, resveratrol and silymarin), cultured probiotic microorganisms and drugs acting through direct/indirect or pleiotropic effects on glycemic control in DM. Among several options, we highlight new promising therapeutic coadjuvants, including chemical scavengers, the probiotic kefir and the phosphodiesterase 5 inhibitors, which besides the reduction of hyperglycemia and ameliorate insulin resistance, they reduce oxidative stress and improve endothelial dysfunction in the systemic vascular circulation. In the near future, experimental studies are expected to clear the intracellular pathways involving coadjuvants. The design of clinical trials may also contribute to new strategies with coadjuvants against the harmful effects of diabetic complications.

Sildenafil prevents renal dysfunction in contrast media-induced nephropathy in Wistar rats.

Contrast-induced nephropathy (CIN) is an iatrogenic medical event in stable cardiology patients that may lead to acute renal failure. There is no current successful therapy to manage CIN. Increasing evidence in experimental models and humans has suggested that this disease is associated with renal tubular and vascular injury triggered by oxidative stress. Considering the importance of reactive oxygen species (ROS) generation in the pathogenesis of CIN, the goal of the present study was to evaluate the effects of sildenafil on CIN development. Male Wistar rats were divided into control, CIN, and CIN pretreated with sildenafil (50 mg/kg/day). CIN was induced by water deprivation, NG-nitro-L-arginine methyl ester + indomethacin injections (10 mg/kg, intraperitoneally) and intravenous iohexol administration (3 g/kg). Renal function was evaluated through glomerular filtration rate (GFR), renal blood flow (RBF), plasma creatinine, uremia, and proteinuria. Oxidative stress was assessed by flow cytometry for intracellular ROS. Treatment with sildenafil attenuated the marked reduction of GFR and RBF in the CIN group. Moreover, sildenafil treatment in CIN rats reduced plasma creatinine, uremia, and proteinuria. Flow cytometry demonstrated that sildenafil attenuated the ROS production in the CIN group. These data suggest that sildenafil may be a new therapeutic agent to prevent CIN through its ability to preserve renal function and attenuate oxidative stress.

Resin from Virola oleifera Protects Against Radiocontrast-Induced Nephropathy in Mice.

Contrast-induced nephropathy (CIN) is an iatrogenic medical event for which there is not yet a successful therapy. Increasing evidence in rodents has suggested that this disease is associated with renal tubular and vascular injury that is triggered directly by oxidative stress. In the present study, we evaluated whether the antioxidant resin from Virola oleifera (RV) could attenuate renal damage in an experimental mouse model of CIN. Adult male Swiss mice were divided into six groups and pre-treated orally with RV (10, 100 and 300 mg/kg), N-acetylcysteine (200 mg/kg) or vehicle for 5 days before the induction of CIN and Control group. Renal function was assessed by measuring plasma creatinine and urea levels. Additionally, renal oxidative stress and apoptosis/cell viability were determined with flow cytometry. Finally, kidney tissues were sectioned for histopathological examination. In this CIN model, pre-treatment with RV improved renal function, lowered the mortality rate, and reduced oxidative stress and apoptosis in both the medulla and cortex renal cells in a dose-dependent manner. Moreover, the RV treatment had beneficial effects on kidney histopathology that were superior to the standard treatment with N-acetylcysteine. These data suggest that because of its antioxidative and antiapoptotic effects and its ability to preserve renal function, resin from Virola oleifera may have potential as a new therapeutic approach for preventing CIN.

Effects of tobacco smoking during pregnancy on oxidative stress in the umbilical cord and mononuclear blood cells of neonates.

BACKGROUND: Although cigarette smoke is known to be a complex mixture of over 4000 substances that can lead to damage through active or passive smoking, its mechanisms and biochemical consequences in pregnancy and neonates are not yet fully understood. Therefore, in the present study, we propose to study the impact of smoking during gestation on the viability of blood mononuclear cells (MNC) from umbilical cords of newborns to assess the degree of oxidative stress and cell viability. After childbirth, the cord blood and the umbilical cord were immediately collected in public hospitals in Greater Vitoria, ES, Brazil. Flow cytometry was used to analyze the cord blood followed by biochemical and histological tests to analyze possible changes in the umbilical cord. RESULTS: Pregnant smokers had a reduction of MNC viability from the umbilical cord (10%), an increase in the production of reactive oxygen species (ROS) and an increase in cell apoptosis (~2-fold) compared to pregnant non-smokers. In the umbilical cord, it was observed an increase of advanced oxidation protein products - AOPP (~2.5-fold) and a loss of the typical architecture and disposition of endothelial cells from the umbilical artery. CONCLUSIONS: These data suggest that maternal cigarette smoking during pregnancy (even in small amounts) may compromise the viability of MNC cells and damage the umbilical cord structure, possibly by excessive ROS bioavailability.

Association of interleukin-6 gene polymorphism with angina pectoris.

In this study, we investigated the role of the -174G>C polymorphism of interleukin-6 (IL-6) as a predisposing factor to angina pectoris. Patients were separated into 2 groups: angina (N = 72) and nonangina (N = 71). There were no statistical differences between groups for all cardiovascular risk factors evaluated. The GG genotype frequency was 18% lower in the angina than in the non-angina group, whereas GC + CC was 18% higher in the angina group (P = .036). The frequency of G allele was 11% lower in the angina than in the nonangina group and C allele was 11% higher in the angina group (P = .043). Patients carrying the C allele showed a 2-fold increased risk for angina pectoris (P = .036). Our study demonstrates a high incidence of the -174G>C polymorphism of the IL-6 gene in patients with angina pectoris compared with those carrying the G allele, reinforcing the contribution of genetic factors to the symptoms of angina pectoris.

Patients with obstructive sleep apnea exhibit impaired endothelial function after myocardial infarction.

BACKGROUND: Impaired brachial flow-mediated dilation (FMD) is associated with risk for subsequent cardiovascular events in patients after myocardial infarction (MI). These patients often have obstructive sleep apnea (OSA). We tested the hypothesis that patients with OSA post MI will exhibit more severe impairment in FMD. METHODS: We studied 64 patients with MI admitted to our hospital. OSA was determined using polysomnography. FMD was measured using high-resolution ultrasonography, with researchers blind to the OSA diagnosis. RESULTS: The mean age was 60 ± 11 years, and the mean BMI was 29 (26, 32 kg/m(2)), 84% of patients were men, 39% had moderate to severe OSA (apnea-hypopnea index [AHI] > 15), and 31% of the patients had mild OSA (5 ≤ AHI < 15). FMD was severely impaired in patients with moderate to severe OSA (0.8% ± 0.7%) as compared with patients without OSA (4.7% ± 0.8%, P = .001) and with mild OSA (3.9% ± 0.8%, P = .015). Linear regression showed that FMD was associated with log nocturnal nadir oxygen saturation (minSaO(2)) (ß = 31.17, P = .0001), age (ß = -0.11, P = .006). MinSaO(2) was an independent predictor of FMD after adjustment for possible confounders (ß = 26.15, P = .001). CONCLUSIONS: FMD is severely impaired in patients with moderate to severe OSA post MI, which may be partially related to nocturnal hypoxemia. Patients with OSA may, therefore, be at higher risk for subsequent cardiovascular events after an MI. Identifying and treating OSA may have important implications in the long-term prognosis of patients post MI. Further studies are necessary to determine if the presence of OSA would affect the long-term occurrence of cardiovascular events after an MI.

Protocolo de pesquisa: o desafio do aprimoramento ético / Research protocol: the challenge of ethical improvement

O trabalho analisa protocolos de pesquisas no âmbito universitário submetidos nos últimos três anos ao Comitê de Ética em Pesquisa da Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória (CEP/Emescam). Este CEP avalia 200 projetos/ano. Os dados foram restritos ao título dos projetos e número de sujeitos. Os achados foram agrupados conforme a Biblioteca Virtual de Saúde (BVS). As pesquisas concentram-se nas categorias saúde do trabalhador; aleitamento materno, saúde materna e da mulher; adolescência, criança e idoso. Economia, indicadores de saúde, alta complexidade e ciência e tecnologia estão ausentes. Considerando que a preferência pela área temática advém da familiaridade com o tema, os dados levantados foram comparados com a experiência dos pesquisadores, registrada na Plataforma Lattes. Sabe-se que hoje as pesquisas são resultado dos esforços passados dos pesquisadores e conhecer o cenário atual da pesquisa acadêmica é importante para planejar o futuro da pesquisa em saúde no país.