Lack of Concordance among Nutritional Diagnostic Methods in Newly Diagnosed Colorectal Cancer Patients.

This study aimed to investigate the concordance of different nutritional assessment methods and the prevalence of inadequate nutritional status in newly diagnosed Colorectal cancer (CRC) patients. Cross sectional study was conducted in a public hospital in Alagoas, Brazil. Clinical, nutritional (patient-generated subjective global assessment [PG-SGA], body mass index [BMI], arm circumference [AC], triceps skinfold [TSF], arm muscle circumference [AMC]) and functional (handgrip strength [HGS]) data were collected from July 2017-January 2019. Of the 31 CRC patients with a mean age of 58.97 ± 14.96 years, 48.4% were elderly and 51.6% were female. TSF adequacy (80.8%) and PG-SGA (80.0%) revealed the highest prevalence of malnutrition. BMI identified the same prevalence of malnutrition and excess weight (30.0%). The concordance between PG-SGA and BMI (kappa = 0.086; p = 0.426) was slight, with fair HGS (kappa = 0.268; p = 0.124). PG-SGA and AC (kappa = 0.015; p = 0.99), TSF (kappa = 0.195; p = 0.558) and AMC adequacy (kappa = 0.142; p = 0.380) were poor. PG-SGA can diagnose malnutrition, even in those who are eutrophic/overweight, by other methods. Various methods do not show concordance with PG-SGA, confirming the need for both objective and subjective methods for better diagnosis of CRC patients.

Biomarkers of placental redox imbalance in pregnancies with preeclampsia and consequent perinatal outcomes.

OBJECTIVE: To compare redox and inflammatory markers between normal and PE-derived placentas and to evaluate the relationship between placental redox imbalance markers and perinatal outcomes in pregnancies with PE. METHODS: This was a cross-sectional study conducted at the maternity hospital of a university hospital in Maceio-Alagoas, Brazil, in 2017, including women diagnosed with PE and healthy pregnant women and their conceptuses. After screening, standardized questionnaires containing socioeconomic, clinical, obstetric and anthropometric data were applied. After delivery, placental samples were collected for quantification of biomarkers of redox imbalance (catalase - CAT; malondialdehyde - MDA; hydrogen peroxide - H2O2; superoxide dismutase - SOD; reduced glutathione - GSH; oxidized glutathione - GSSG; and their ratio - GSH/GSSG) and inflammation (myeloperoxidase - MPO; interleukin (IL)-6; IL-8; IL-10; and tumor necrosis factor-alpha - TNF-α). All biomarkers were evaluated via linear regression with adjustments of variables with measures of weight, length, head circumference (HC), chest circumference (CC) and gestational age of newborns at birth, considering p < 0.05 as significant. RESULTS: A total of 100 pregnant women with PE and 50 healthy pregnant women were studied. Higher placental levels of catalase (p = 0.018), SOD (p = 0.031), the GSH/GSSG ratio (p = 0.019) and IL-6 (p = 0.010) and lower GSSG (p = 0.001) were observed in pregnant women with PE than in the control group. Positive associations between placental GSH levels and body weight, HC, CC and gestational age at birth (p < 0.05) were identified. CONCLUSION: PE-derived placentas had high concentrations of some antioxidants (enzymes and thiols), which might be a compensation mechanism against oxidative stress. Placental GSH levels were the only biomarker, among the studied ones, related positively with beneficial perinatal outcomes, suggesting that this endogenous antioxidant plays an important role in maintaining the health of the conceptus and women with PE.

Polyphenol profile by UHPLC-MS/MS, anti-glycation, antioxidant and cytotoxic activities of several samples of propolis from the northeastern semi-arid region of Brazil.

CONTEXT: Propolis has promising biological activities. Propolis samples from the Northeast of Bahia, Brazil - sample A from Ribeira do Pombal and B, from Tucano - were investigated, with new information regarding their biological activities. OBJECTIVE: This paper describes the chemical profile, antioxidant, anti-glycation and cytotoxic activities of these propolis samples. MATERIAL AND METHODS: Ethanol extracts of these propolis samples (EEP) and their fractions were analyzed to determine total phenolic content (TPC); antioxidant capacity through DPPH•, FRAP and lipid peroxidation; anti-glycation activity, by an in vitro glucose (10 mg/mL) bovine serum albumine (1 mg/mL) assay, during 7 d; cytotoxic activity on cancer (SF295, HCT-116, OVCAR-8, MDA-MB435, MX-1, MCF7, HL60, JURKAT, MOLT-4, K562, PC3, DU145) and normal cell lines (V79) at 0.04-25 µg/mL concentrations, for 72 h. The determination of primary phenols by ultra high-pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) and volatile organic compounds content by gas chromatography-mass spectrometry (GC-MS) were also performed. RESULTS: The EEP polar fractions exhibited up to 90% protection against lipid peroxidation. The IC50 value for anti-glycation activity of EEP was between 16.5 and 19.2 µg/mL, close to aminoguanidine (IC50 = 7.7 µg/mL). The use of UHPLC-MS/MS and GC-MS allowed the identification of 12 bioactive phenols in the EEP and 24 volatile compounds, all already reported. CONCLUSIONS: The samples present good antioxidant/anti-glycation/cytotoxic activities and a plethora of biologically active compounds. These results suggest a potential role of propolis in targeting ageing and diseases associated with oxidative and carbonylic stress, aggregating value to them.

Meta-analysis of studies on chemical, physical and biological agents in the control of Aedes aegypti.

BACKGROUND: Aedes aegypti is a vector of international concern because it can transmit to humans three important arboviral diseases: yellow fever, dengue and chikungunya. Epidemics that are repeated year after year in a variety of urban centers indicate that there are control failures, allowing the vector to continue expanding. METHODS: To identify the most effective vector control strategies and the factors that contributed to the success or failure of each strategy, we carried out a systematic review with meta-analysis of articles published in 12 databases, from 1974 to the month of December 2013. We evaluated the association between the use of whatever chemical substance, mechanical agent, biological or integrated actions against A. aegypti and the control of the vector, as measured by 10 indicators. RESULTS: We found 2,791 articles, but after careful selection, only 26 studies remained for analysis related to control interventions implemented in 15 countries, with 5 biological, 5 chemical, 3 mechanical and 13 integrated strategies. The comparison among all of them, indicated that the control of A. aegypti is significantly associated with the type of strategy used, and that integrated interventions consist of the most effective method for controlling A. aegypti. CONCLUSIONS: The most effective control method was the integrated approach, considering the influence of eco-bio-social determinants in the virus-vector-man epidemiological chain, and community involvement, starting with community empowerment as active agents of vector control.

Antiplasmodial activity of iron(II) and ruthenium(II) organometallic complexes against Plasmodium falciparum blood parasites.

This work reports the in vitro activity against Plasmodium falciparum blood forms (W2 clone, chloroquine-resistant) of tamoxifen-based compounds and their ferrocenyl (ferrocifens) and ruthenocenyl (ruthenocifens) derivatives, as well as their cytotoxicity against HepG2 human hepatoma cells. Surprisingly with these series, results indicate that the biological activity of ruthenocifens is better than that of ferrocifens and other tamoxifen-like compounds. The synthesis of a new metal-based compound is also described. It was shown, for the first time, that ruthenocifens are good antiplasmodial prototypes. Further studies will be conducted aiming at a better understanding of their mechanism of action and at obtaining new compounds with better therapeutic profile.

Oxidative Stress and Inflammation in Hepatic Diseases: Therapeutic Possibilities of N-Acetylcysteine.

Liver disease is highly prevalent in the world. Oxidative stress (OS) and inflammation are the most important pathogenetic events in liver diseases, regardless the different etiology and natural course. N-acetyl-l-cysteine (the active form) (NAC) is being studied in diseases characterized by increased OS or decreased glutathione (GSH) level. NAC acts mainly on the supply of cysteine for GSH synthesis. The objective of this review is to examine experimental and clinical studies that evaluate the antioxidant and anti-inflammatory roles of NAC in attenuating markers of inflammation and OS in hepatic damage. The results related to the supplementation of NAC in any form of administration and type of study are satisfactory in 85.5% (n = 59) of the cases evaluated (n = 69, 100%). Within this percentage, the dosage of NAC utilized in studies in vivo varied from 0.204 up to 2 g/kg/day. A standard experimental design of protection and treatment as well as the choice of the route of administration, with a broader evaluation of OS and inflammation markers in the serum or other biological matrixes, in animal models, are necessary. Clinical studies are urgently required, to have a clear view, so that, the professionals can be sure about the effectiveness and safety of NAC prescription.

Evaluation of the role of ATP-binding cassette transporters as a defence mechanism against temephos in populations of Aedes aegypti.

The role of ATP-binding cassette (ABC) transporters in the efflux of the insecticide, temephos, was assessed in the larvae of Aedes aegypti. Bioassays were conducted using mosquito populations that were either susceptible or resistant to temephos by exposure to insecticide alone or in combination with sublethal doses of the ABC transporter inhibitor, verapamil (30, 35 and 40 µM). The best result in the series was obtained with the addition of verapamil (40 µM), which led to a 2x increase in the toxicity of temephos, suggesting that ABC transporters may be partially involved in conferring resistance to the populations evaluated.

Structural changes in hemoglobin and glycation.

Hemoglobin (Hb) is a hemeprotein found inside erythrocytes and is crucial in transporting oxygen and carbon dioxide in our bodies. In erythrocytes (Ery), the main energy source is glucose metabolized through glycolysis. However, a fraction of Hb can undergo glycation, in which a free amine group from the protein spontaneously binds to the carbonyl of glucose in the bloodstream, resulting in the formation of glycated hemoglobin (HbA1c), widely used as a marker for diabetes. Glycation leads to structural and conformational changes, compromising the function of proteins, and is intensified in the event of hyperglycemia. The main changes in Hb include structural alterations to the heme group, compromising its main function (oxygen transport). In addition, amyloid aggregates can form, which are strongly related to diabetic complications and neurodegenerative diseases. Therefore, this chapter discusses in vitro protocols for producing glycated Hb, as well as the main techniques and biophysical assays used to assess changes in the protein's structure before and after the glycation process. This more complete understanding of the effects of glycation on Hb is fundamental for understanding the complications associated with hyperglycemia and for developing more effective prevention and treatment strategies.

Effect of Curcumin Plus Piperine on Redox Imbalance, Fecal Calprotectin and Cytokine Levels in Inflammatory Bowel Disease Patients: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

The development and course of inflammatory bowel disease (IBD) are significantly influenced by inflammation and oxidative stress. Antioxidant therapy is a promising therapeutic option to enhance the clinical results of these individuals in this particular scenario. The purpose of this study is to assess the impact of curcumin, with or without piperine, on cytokines, fecal calprotectin (CalF), and oxidative stress enzymatic and non-enzymatic indicators in patients with IBD. METHODS: Patients with Crohn's disease (CD) or ulcerative colitis (UC) who were at least 18 years old and had intact liver and kidney function participated in this randomized, double-blind trial (trial registration: ensaiosclinicos.gov.br as RBR-89q4ydz). For 12 weeks, participants were randomly assigned to one of three groups: placebo, curcumin (1000 mg/day), or curcumin plus piperine (1000 mg + 10 mg/day). In order to examine oxidative stress indicators, CalF, and pro-inflammatory cytokines, blood and fecal samples were obtained, both prior to and following the intervention time. RESULTS: After adjusting for age, sex, and type of IBD, the curcumin plus piperine group had substantially higher serum levels of superoxide dismutase (SOD) than the placebo group (4346.9 ± 879.0 vs. 3614.5 ± 731.5; p = 0.041). There were no discernible variations between the groups in CalF, inflammatory markers, or other indicators of oxidative stress. CONCLUSIONS: In patients with inflammatory bowel disease (IBD), our study indicates that a 12-week curcumin plus piperine treatment effectively increases enzymatic antioxidant defense, especially SOD. These results demonstrate the potential therapeutic benefits of managing redox imbalance in individuals with IBD.

Extraintestinal Manifestations in Induced Colitis: Controversial Effects of N-Acetylcysteine on Colon, Liver, and Kidney.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease (IBD) characterized by continuous inflammation in the colonic mucosa. Extraintestinal manifestations (EIM) occur due to the disruption of the intestinal barrier and increased permeability caused by redox imbalance, dysbiosis, and inflammation originating from the intestine and contribute to morbidity and mortality. The aim of this study is to investigate the effects of oral N-acetylcysteine (NAC) on colonic, hepatic, and renal tissues in mice with colitis induced by dextran sulfate sodium (DSS). Male Swiss mice received NAC (150 mg/kg/day) in the drinking water for 30 days before and during (DSS 5% v/v; for 7 days) colitis induction. On the 38th day, colon, liver, and kidney were collected and adequately prepared for the analysis of oxidative stress (superoxide dismutase (SOD), catalase (CAT), glutathione reduced (GSH), glutathione oxidized (GSSG), malondialdehyde (MDA), and hydrogen peroxide (H2O2)) and inflammatory biomarkers (myeloperoxidase (MPO) -, tumor necrosis factor alpha - (TNF-α, and interleukin-10 (IL-10)). In colon, NAC protected the histological architecture. However, NAC did not level up SOD, in contrast, it increased MDA and pro-inflammatory effect (increased of TNF-α and decreased of IL-10). In liver, colitis caused both oxidative (MDA, SOD, and GSH) and inflammatory damage (IL-10). NAC was able only to increase GSH and GSH/GSSG ratio. Kidney was not affected by colitis; however, NAC despite increasing CAT, GSH, and GSH/GSSG ratio promoted lipid peroxidation (increased MDA) and pro-inflammatory action (decreased IL-10). Despite some beneficial antioxidant effects of NAC, the negative outcomes concerning irreversible oxidative and inflammatory damage in the colon, liver, and kidney confirm the nonsafety of the prophylactic use of this antioxidant in models of induced colitis, suggesting that additional studies are needed, and its use in humans not yet recommended for the therapeutic routine of this disease.

Pain Assessment and Acute Phase Response in Donkeys Submitted to Inguinal Orchiectomy.

In most animals, pain can compromise physiological functions and delay healing so, rapid detection of pain through behavior and inflammatory reaction with biomarkers are necessary. This study aimed to evaluate pain, physiological variations and Acute Phase Proteins (APP) in donkeys undergoing orchiectomy technique by inguinal access. For this research, 15 male northeastern donkeys kept in extensive management were selected, with a mean age of 4.5±3.1 years. All animals had the same anesthetic protocol, using dissociative anesthesia and local block with lidocaine, followed by orchiectomy by inguinal access. Due to their predisposition to complications, the inguinal technique is the most indicated to minimize complications and excessive inflammation in donkeys' orchiectomy, the donkeys were evaluated regarding behavioral assessment of pain, hematological parameters, APP and the surgical wound, during 0 hour, 24 hours, 48 hours and 72 hours. As for the physiological parameters and APP, no significant differences were observed between times, due to the use of nonsteroidal antiinflammatory drugs. In the macroscopic evaluation of the surgical wound, it was observed that there were no significant differences between the times, with animals presenting mean scores of 1.8±0.414, in 48 hours 1.6 ± 0.507, and in 72 hours 1.6 ± 0.507. Most animals had mild to moderate edema in the scrotum and foreskin regions. As for pain assessment, the average scores were between 2 and 3, representing mild and moderate pain, not requiring intervention. However, further research is needed to elucidate the behavior of PFAs in the face of variables and the creation of new pain scales for animals raised in an extensive system.

Antioxidant Therapy in Inflammatory Bowel Disease: A Systematic Review and a Meta-Analysis of Randomized Clinical Trials.

The objective of this study is to assess the effectiveness of treatment for inflammatory bowel diseases in modulating oxidative stress biomarkers and cytokine levels. A systematic review of clinical trials was conducted, searching electronic databases including PubMed, Science Direct, and Scopus. After excluding articles that did not meet the inclusion criteria, 19 studies were included in the systematic review and 8 in the meta-analysis (6 for antioxidant capacity, 6 for superoxide dismutase (SOD), and 5 for lipid peroxidation analyzed through malondialdehyde (MDA) levels). SOD was significantly modulated (RR = 0.3764, 95% CI [0.0262 to 0.7267], p = 0.035) but not antioxidant capacity (RR = 0.3424, 95% CI [0.0334 to 0.7183], p = 0.0742) or MDA (RR = -0.8534, 95% CI [-1.9333 to 0.2265], p = 0.1214). Nonetheless, studies investigating oxidative stress biomarkers and cytokines in the context of alternative therapies for IBD treatment are still scarce. This review highlights the potential of antioxidant supplementation in IBD management and underscores the need for further investigations into its effects on oxidative stress biomarkers and cytokines to improve therapeutic approaches for IBD patients.

The impact on colostrum oxidative stress, cytokines, and immune cells composition after SARS-CoV-2 infection during pregnancy.

Background: Limited data are available regarding the differences between immunological, biochemical, and cellular contents of human colostrum following maternal infection during pregnancy with coronavirus 2 disease (COVID-19). Objective: To investigate whether maternal COVID-19 infection may affect immunological, biochemical, and cellular contents of human colostrum. Methods: Using a case-control study design, we collected colostrum from 14 lactating women with a previous diagnosis of COVID-19 during pregnancy and 12 without a clear diagnosis during September 2020 to May 2021. Colostrum samples were analysed for some enzymes and non-enzymatic oxidative stress markers (SOD, CAT, GPx, MDA, GSH, GSSG, H2O2, MPO) and for IL-1ß, IL-6, tumour necrosis factor (TNF)-α, protein induced by interferon gamma (IP)-10, IL-8, IFN-λ1, IL12p70, IFN-α2, IFN-λ2/3, granulocyte macrophage colony stimulating factor (GM-CSF), IFN-ß, IL-10 and IFN-γ, along with IgA and IgG for the SARS-CoV-2 S protein. We perform immunophenotyping to assess the frequency of different cell types in the colostrum. Results: Colostrum from the COVID-19 symptomatic group in pregnancy contained reduced levels of H2O2, IFN-α2, and GM-CSF. This group had higher levels of GSH, and both NK cell subtypes CD3-CD56brightCD16-CD27+IFN-γ+ and CD3-CD56dimCD16+CD27- were also increased. Conclusion: The present results reinforce the protective role of colostrum even in the case of mild SARS-Cov-2 infection, in addition to demonstrating how adaptive the composition of colostrum is after infections. It also supports the recommendation to encourage lactating women to continue breastfeeding after COVID-19 illness.

Gestational Diabetes Mellitus: The Crosslink among Inflammation, Nitroxidative Stress, Intestinal Microbiota and Alternative Therapies.

Gestational diabetes mellitus (GDM) is characterized by a set of metabolic complications arising from adaptive failures to the pregnancy period. Estimates point to a prevalence of 3 to 15% of pregnancies. Its etiology includes intrinsic and extrinsic aspects of the progenitress, which may contribute to the pathophysiogenesis of GDM. Recently, researchers have identified that inflammation, oxidative stress, and the gut microbiota participate in the development of the disease, with potentially harmful effects on the health of the maternal-fetal binomial, in the short and long terms. In this context, alternative therapies were investigated from two perspectives: the modulation of the intestinal microbiota, with probiotics and prebiotics, and the use of natural products with antioxidant and anti-inflammatory properties, which may mitigate the endogenous processes of the GDM, favoring the health of the mother and her offspring, and in a future perspective, alleviating this critical public health problem.

Interleukin-6 and triceps skinfold are associated with severity/cancer stage in newly-diagnosed colorectal cancer patients.

INTRODUCTION: Introduction: colorectal cancer (CRC) has an important impact on morbidity and mortality globally, and nitroxidative stress, inflammation, and nutritional status are linked with its progression. Aim: to analyze the association of inflammatory, anthropometric, functional, and oxidative markers with tumor stage in newly-diagnosed CRC patients at a public reference center in Maceió, Alagoas, Brazil. Methods: patient-generated subjective global assessment was applied, and weight, height, arm circumference, triceps skinfold (TSF), arm muscle circumference, and handgrip strength were obtained. A fasting blood sample was collected, centrifuged, and the serum was stored at -80 °C until the analysis. Malonaldehyde levels were quantified by HPLC (high-performance liquid chromatography) and cytokines, namely tumor necrosis factor-alpha, and interleukins IL-6, IL-8, and IL-17 were analyzed by ELISA. Patients were grouped according to cancer stage into group 1 (stage 0-III) and group 2 (stage IV). A binary logistic regression analysis was performed, adjusted for sex and age, to assess the relationships between the variables studied and cancer stage. Significance was considered when p < 0.05. Results: twenty-eight CRC patients were included, twenty (71.4 %) from group 1 and eight (28.6 %) from group 2. The binary logistic regression revealed that lower TSF adequacy (OR = 0.929; CI 95 % = 0.870-0.993; p = 0.029) and higher IL-6 levels (OR = 1.001; CI 95 % = 1.000-1.002; p = 0.012) increased the chance of patients having tumor stage IV. Conclusion: These data support that IL-6 and TSF may help in cancer stage assessment in clinical practice. Modulation of inflammation by IL-6 levels may be a target in CRC treatment.

INTRODUCCIÓN: Introducción: el cáncer colorrectal (CCR) tiene un impacto importante en la morbilidad y mortalidad a nivel mundial, y el estrés nitroxidativo, la inflamación y el estado nutricional están relacionados con su progresión. Objetivos: analizar la asociación de los marcadores inflamatorios, antropométricos, funcionales y oxidativos con el estadio tumoral de pacientes con CCR recién diagnosticados en un centro público de referencia de Maceió, Alagoas, Brasil. Métodos: se aplicó la valoración global subjetiva generada por el paciente y se obtuvieron el peso, la altura, la circunferencia del brazo, el pliegue cutáneo del tríceps (PCT), la circunferencia del músculo del brazo y la fuerza de prensión. Se tomó una muestra de sangre en ayunas, se centrifugó y el suero se almacenó a -80 °C hasta el momento del análisis. Los niveles de malonaldehído se cuantificaron por CLAR (cromatografía líquida de alta resolución) y las citocinas, representadas por el factor de necrosis tumoral alfa y las interleucinas IL-6, IL-8 e IL-17, se analizaron mediante ELISA. Los pacientes se agruparon según el estadio del cáncer en grupo 1 (estadio 0-III) y grupo 2 (estadio IV). Se realizó una regresión logística binaria, ajustada por sexo y edad, para evaluar las relaciones entre las variables estudiadas y el estadio del cáncer. Se consideró la significancia cuando p < 0,05. Resultados: se incluyeron veintiocho pacientes con CCR, de los cuales veinte (71,4 %) eran del grupo 1 y ocho (28,6 %) del grupo 2. La regresión logística binaria reveló que una menor adecuación de PCT (OR = 0,929; IC 95 % = 0,870-0,993; p = 0,029) y los niveles más altos de IL-6 (OR = 1,001; IC 95 % = 1,000-1,002; p = 0,012) aumentaban la probabilidad de que los pacientes tuvieran un tumor en estadio IV. Conclusiones: estos datos señalan que la IL-6 y el PCT pueden ayudar en la evaluación del estadio del cáncer en la práctica clínica. La modulación de la inflamación por los niveles de IL-6 podría ser una diana en el tratamiento del CCR.

N-Acetylcysteine (NAC): Impacts on Human Health.

N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several diseases related to oxidative stress and inflammation. The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH), which is the most crucial biothiol responsible for cellular redox imbalance. As an anti-inflammatory compound, NAC can reduce levels of tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1ß) by suppressing the activity of nuclear factor kappa B (NF-κB). Despite NAC's relevant therapeutic potential, in several experimental studies, its effectiveness in clinical trials, addressing different pathological conditions, is still limited. Thus, the purpose of this chapter is to provide an overview of the medicinal effects and applications of NAC to human health based on current therapeutic evidence.

Biomarkers of Inflammation and Redox Imbalance in Umbilical Cord in Pregnancies with and without Preeclampsia and Consequent Perinatal Outcomes.

OBJECTIVE: To compare redox imbalance and inflammation biomarkers in umbilical cords from pregnancies with and without preeclampsia (PE) and to analyse their relationships with perinatal outcomes. METHODS: A controlled cross-sectional study was conducted in Maceió, Alagoas, Brazil, that involved pregnant women with PE and a group of women without the disease, through the application of a standardized questionnaire. After delivery, umbilical cord samples were collected to measure antioxidant defense, products from oxidative damage, and inflammation biomarkers such as myeloperoxidase (MPO), interleukin- (IL-) 6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α). Statistical analyses were performed using Stata version 13.0 software and IBM Statistical Package for the Social Sciences (SPSS) 20.0, adopting a 95% confidence level (α = 0.05), with the chi-square test, the Wilcoxon-Mann-Whitney test, and the multinomial and Poisson regression tests. RESULTS: One hundred PE pregnant women and 50 women without the disease were studied. The umbilical cords from PE pregnancies showed higher levels of reduced glutathione (GSH) (p ≤ 0.001), glutathione peroxidase (GPx) (p = 0.016), and malondialdehyde (MDA) (p = 0.028) and lower levels of IL-6 (p = 0.030) and TNF-α (p ≤ 0.001) than the other group, with some associations among these biomarkers with perinatal outcomes. CONCLUSION: The higher levels of GSH and GPx, in addition to the lower levels of IL-6 and TNF-α, found in the PE umbilical cord, may result from adaptive mechanisms to maintain the oxidative and inflammatory balance; however, despite these changes, the damage to the cell membranes was not minimized, as the MDA level was higher in women with PE than in women without the disease. This implies that a redox imbalance is present, confirming that other physiological and adaptive mechanisms are being activated to preserve foetal health. Therefore, the present work unveils an important role of the umbilical cord in controlling redox imbalance and inflammation in PE pregnancies. Our results reinforce the necessity for continuous research on GSH as a protective compound for the perinatal outcome, especially in PE women.

Photoluminescent nanoprobes based on thiols capped CdTe quantum dots for direct determination of thimerosal in vaccines.

CdTe quantum dots (CdTe QD) have been produced at different times of synthesis (1, 2, and 4 h) using thiols as capping agents: mercaptopropionic acid (MPA), mercaptosuccinic acid (MSA) and N-acetyl-l-cysteine (NAC) using water as a solvent. The produced CdTe QD were characterized by UV-vis and photoluminescence (PL) spectroscopy and showed a relationship among reflux time, size, and spectroscopic properties. CdTe QD were shown to interact with thimerosal (TM), an organic mercury compound, and the PL intensity was effectively quenched, characterizing an ON-OFF process. However, the NAC capped CdTe (CdTe-NAC) at 1 h presented the best sensitivity for TM determination. Under optimized conditions, a linear range from 0.1 to 1.0 µg mL-1 (0.25-2.5 µM) and a LOD of 26.6 µg L-1 (66.7 nM) were achieved. The influence of different mercuric species [Hg(II), methylmercury, ethylmercury, and phenylmercury], along with thiosalicylic acid (TSA), and other ionic species on the sensitivity of the method and the interaction mechanism between TM and CdTe-NAC have been discussed. The method was successfully applied for direct quantification of TM in vaccines, and the results were validated by cold vapor atomic fluorescence spectroscopy (CV AFS). Finally, the proposed method proved to be fast, sensitive, and simple for suitable use in vaccine quality control.

Electrochemical evidence of nitrate release from the nitrooxy compound 4-((nitrooxy) methyl)-3-nitrobenzoic acid and its antinociceptive and anti-inflammatory activities in mice.

Considering the many biological activities of nitric oxide (NO), some lines of research focused on the modulation of these activities through the provision of this mediator by designing and synthesizing compounds coupled with an NO donor group. Thus, the objectives of the present study were to carry out an electrochemical investigation of the nitrooxy compound 4-((nitrooxy) methyl)-3-nitrobenzoic acid (1) and evaluate its activities and putative mechanisms in experimental models of pain and inflammation. Voltammetric studies performed in aprotic medium (mimetic of membranes) showed important electrochemical reduction mechanisms: nitroaromatic reduction, self-protonation, and finally reductive elimination, which leads to nitrate release. Systemic administration of the nitrooxy compound (1) inhibited the nociceptive response induced by heat and the tactile hypersensitivity and paw edema induced by carrageenan in mice. The activities in the models of inflammatory pain and edema were associated with reduced neutrophil recruitment and production of inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, tumor necrosis factor-α and CXCL-1, and increased production of IL-10. Concluding, electrochemical analysis revealed unequivocally that electron transfer at the nitro group of the nitrooxy compound (1) results in the cleavage of the organic nitrate, potentially resulting in the generation of NO. This electrochemical mechanism may be compared to a biochemical electron-transfer mediated nitrate release that, by appropriate in vivo bioreduction (enzymatic or not) would lead to NO production. Compound (1) exhibits activities in models of inflammatory pain and edema that may be due to reduced recruitment of neutrophils and production of inflammatory cytokines and increased production of IL-10. These results reinforce the interest in the investigation of NO donor compounds as candidates for analgesic and anti-inflammatory drugs.

The Close Interplay of Nitro-Oxidative Stress, Advanced Glycation end Products and Inflammation in Inflammatory Bowel Diseases.

BACKGROUND: Inflammatory Bowel Disease (IBD) exhibits no defined aetiology. However, factors such as genetic and nitro-oxidative stress are associated with chronic inflammation and IBD progression to Colorectal Cancer (CRC). The present review discusses the association of nitro-oxidative stress, inflammation and Advanced Glycation End products (AGE) and their corresponding receptor (RAGE) in IBD and examines the connection between these factors and nuclear factors, such as Nuclear Factor Kappa B (NF-κB), factorerythroid 2-related factor-2 (Nrf2), and p53 Mutant (p53M). METHODS: We searched the PubMed, ScienceDirect and Web of Science databases using a combination of the following terms: IBD, CRC, oxidative stress, inflammation, NF-κB, Nrf2, p53M, AGE and RAGE. RESULTS: Oxidative stress and inflammation activated two cellular pathways, the nuclear expression of pro-inflammatory, pro-oxidant and pro-oncogenic genes based on NF-κB and p53M, which is associated with NF-κB activation, Deoxyribonucleic acid (DNA) damage and the expression of pro-oncogenic genes. Nrf2 stimulates the nuclear expression of enzymatic and non-enzymatic antioxidant systems and anti-inflammatory genes, and is inhibited by chronic oxidative stress, NF-κB and p53M. AGE/RAGE are involved in inflammation progression because RAGE polymorphisms and increased RAGE levels are found in IBD patients. Alterations of these pathways in combination with oxidative damage are responsible for IBD symptoms and the progression to CRC. CONCLUSION: IBD is an inflammatory and nitro-oxidative stress-based bowel disease. Achieving a molecular understanding of the biochemical events and their complicated interactions will impact basic and applied research, animal models, and clinical trials.