Increased nitro-oxidative toxicity in association with metabolic syndrome, atherogenicity and insulin resistance in patients with affective disorders.

BACKGROUND: There is a strong comorbidity between mood disorders and metabolic syndrome (MetS). Increased levels of reactive oxygen and nitrogen species (RONS) and nitro-oxidative stress toxicity (NOSTOX) partially underpin this comorbidity. AIMS: To examine the associations of RONS/NOSTOX biomarkers with MetS after adjusting for the significant effects of mood disorders (major depression, and bipolar type 1 and 2), generalized anxiety disorder (GAD), tobacco use disorder (TUD), and male sex. METHODS: The study included subjects with (n=65) and without (n=107) MetS and measured levels of superoxide dismutase 1 (SOD1), lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) and computed z unit-weighted composite scores which reflect RONS/NOSTOX. The study included 105 patients with mood disorders, 46 with GAD, and 95 with TUD. RESULTS: MetS was associated with increased levels of MDA and AOPP, independently from mood disorders, TUD, sex and GAD. Atherogenicity and insulin resistance (IR) were significantly associated with a NOSTOX composite score. Mood disorders, TUD, GAD, male sex and MetS independently contribute to increased RONS/NOSTOX. The RONS/NOSTOX profile of MetS was different from that of GAD, which showed increased SOD1 and NOx levels. TUD was accompanied by increased SOD1, LOOH and MDA, and male sex by increased LOOH and AOPP. CONCLUSIONS: MetS is characterized by increased lipid peroxidation with aldehyde formation and chlorinative stress, and atherogenicity and IR are strongly mediated by RONS/NOSTOX. Partially shared RONS/NOSTOX pathways underpin the comorbidity of MetS with mood disorders, GAD, and TUD.

Association of -94 ATTG insertion/deletion NFkB1 and c.*126G>A NFkBIA genetic polymorphisms with oxidative and nitrosative stress biomarkers in Brazilian subjects with Parkinson's Disease.

Parkinson's disease (PD) is a complex neurodegenerative disorder, resulting dopaminergic neuronal cell death in the substantia nigra. The disease is characterized by major motor impairment, being bradykinesia, rest tremor, rigidity and loss of postural reflexes the most common, while autonomic dysfunctions, sleep disturbances and psychiatric disorders are some of the wide range of non-motor symptoms. Several processes have been identified to be associated with disease development, such as mitochondrial dysfunction, oxidative/nitrosative stress and neuroinflammation. NF-κB is an important transcription factor that regulates several inflammatory elements and pathways, and polymorphisms on NFKB1 and NFKBIA genes can potentially influence redox balance towards a pro-oxidative frame, modulating disease progression. Evaluation of these polymorphisms in the redox status of PD subjects could provide new insights on the pathogenesis of this disorder. The study aimed to test associations of -94 in./del ATTG NFKB1 (rs28362491) and c.*126G > A NFKBIA (rs696) polymorphisms with PD development, and to test the influence of both polymorphisms on oxidative/nitrosative stress (OS/NS) parameters. A total of 110 Brazilian individuals were enrolled, being 55 subjects recruited from University Hospital of Londrina as the PD group, and 55 subjects matched for age, sex and ethnicity composed the healthy control (HC) group. NFkB1 and NFkBIA polymorphisms were genotyped by PCR-RFLP. Lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), sulfhydryl groups (SH), total radical trapping antioxidant parameter (TRAP) and paraoxonase-1 activity (PON-1) were assessed. Despite no association of polymorphisms on disease development was observed, in PD subjects the NFKB1 del/del genotype was associated with higher levels of LOOH, while NFkBIA GA and AA genotypes were associated with higher NOx levels, suggesting that NFkB plays a role in PD susceptbility. In conclusion, the prospect of genetic polymorphisms of elements involved in inflammation and OS/NS might be a new approach to unravel PD etiology.

Major Differences in Neurooxidative and Neuronitrosative Stress Pathways Between Major Depressive Disorder and Types I and II Bipolar Disorder.

Accumulating evidence indicates that oxidative and nitrosative stress (O&NS) pathways play a key role in the pathophysiology of bipolar disorder (BD) and major depressive disorder (MDD). However, only a handful of studies have directly compared alterations in O&NS pathways among patients with MDD and BD types I (BPI) and BPII. Thus, the current study compared superoxide dismutase (SOD1), lipid hydroperoxides (LOOH), catalase, nitric oxide metabolites (NOx), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) between mood disorder patients in a clinically remitted state. To this end 45, 23, and 37 participants with BPI, BPII, and MDD, respectively, as well as 54 healthy controls (HCs) were recruited. Z-unit weighted composite scores were computed as indices of reactive oxygen species (ROS) production and nitro-oxidative stress driving lipid or protein oxidation. SOD1, NOx, and MDA were significantly higher in MDD than in the other three groups. AOPP was significantly higher in BPI than in HCs and BPII patients. BPII patients showed lower SOD1 compared to all other groups. Furthermore, MDD was characterized by increased indices of ROS and lipid hydroperoxide production compared to BPI and BPII groups. Indices of nitro-oxidative stress coupled with aldehyde production or protein oxidation were significantly different among the three patient groups (BDII > BDI > MDD). Finally, depressive symptom scores were significantly associated with higher LOOH and AOPP levels. In conclusion, depression is accompanied by increased ROS production, which is insufficiently dampened by catalase activity, thereby increasing nitro-oxidative damage to lipids and aldehyde production. Increased protein oxidation with formation of AOPP appeared to be hallmark of MDD and BPI. In addition, patients with BPII may have protection against the damaging effects of ROS including lipid peroxidation and aldehyde formation. This study suggests that biomarkers related to O&NS could aid in the differentiation of MDD, BPI, and BPII.

Metabolic syndrome components are associated with oxidative stress in overweight and obese patients.

OBJECTIVE: The aim of this study is to evaluate the influence of the body mass index (BMI) and the metabolic syndrome (MetS) parameters on oxidative and nitrosative stress in overweight and obese subjects. SUBJECTS AND METHODS: Individuals were divided into three groups: the control group (G1, n = 131) with a BMI between 20 and 24.9 kg/m2, the overweight group (G2, n = 120) with a BMI between 25 and 29.9 kg/m2 and the obese group (G3, n = 79) with a BMI ≥ 30 kg/m2. RESULTS: G3 presented higher advanced oxidation protein products (AOPPs) in relation to G1 and G2 (p = 0.001 and p = 0.011, respectively) whereas G2 and G3 had lower levels of nitric oxide (NO) (p = 0.009 and p = 0.048, respectively) compared to G1. Adjusted for the presence of MetS to evaluate its influence, the levels of AOPPs did not differ between the groups, whereas NO remained significantly lower. Data adjusted by the BMI showed that subjects with higher triacylglycerol levels had higher AOPPs (p = 0.001) and decreased total radical-trapping antioxidant parameter/uric Acid (p = 0.036). Subjects with lower high-density lipoprotein (HDL) levels and patients with higher blood pressure showed increased AOPPs (p = 0.001 and p = 0.034, respectively) and lower NO levels (p = 0.017 and p = 0.043, respectively). Subjects who presented insulin resistance had higher AOPPs (p = 0.024). CONCLUSIONS: Nitrosative stress was related to BMI, and protein oxidation and nitrosative stress were related to metabolic changes and hypertension. MetS components were essential participants in oxidative and nitrosative stress in overweight and obese subjects.

Generalized Anxiety Disorder (GAD) and Comorbid Major Depression with GAD Are Characterized by Enhanced Nitro-oxidative Stress, Increased Lipid Peroxidation, and Lowered Lipid-Associated Antioxidant Defenses.

Accumulating evidence shows that nitro-oxidative pathways play an important role in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD) and maybe anxiety disorders. The current study aims to examine superoxide dismutase (SOD1), catalase, lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), malondialdehyde (MDA), glutathione (GSH), paraoxonase 1 (PON1), high-density lipoprotein cholesterol (HDL), and uric acid (UA) in participants with and without generalized anxiety disorder (GAD) co-occurring or not with BD, MDD, or tobacco use disorder. Z unit-weighted composite scores were computed as indices of nitro-oxidative stress driving lipid and protein oxidation. SOD1, LOOH, NOx, and uric acid were significantly higher and HDL and PON1 significantly lower in participants with GAD than in those without GAD. GAD was more adequately predicted by increased SOD + LOOH + NOx and lowered HDL + PON1 composite scores. Composite scores of nitro-oxidative stress coupled with aldehyde and AOPP production were significantly increased in participants with comorbid GAD + MDD as compared with all other study groups, namely MDD, GAD + BD, BD, GAD, and healthy controls. In conclusion, GAD is characterized by increased nitro-oxidative stress and lipid peroxidation and lowered lipid-associated antioxidant defenses, while increased uric acid levels in GAD may protect against aldehyde production and protein oxidation. This study suggests that increased nitro-oxidative stress and especially increased SOD1 activity, NO production, and lipid peroxidation as well as lowered HDL-cholesterol and PON1 activity could be novel drug targets for GAD especially when comorbid with MDD.

Increased Root Canal Endotoxin Levels are Associated with Chronic Apical Periodontitis, Increased Oxidative and Nitrosative Stress, Major Depression, Severity of Depression, and a Lowered Quality of Life.

Evidence indicates that major depression is accompanied by increased translocation of gut commensal Gram-negative bacteria (leaky gut) and consequent activation of oxidative and nitrosative (O&NS) pathways. This present study examined the associations among chronic apical periodontitis (CAP), root canal endotoxin levels (lipopolysaccharides, LPS), O&NS pathways, depressive symptoms, and quality of life. Measurements included advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), lipid peroxides (LOOH), -sulfhydryl (SH) groups, total radical trapping antioxidant parameter (TRAP), and paraoxonase (PON)1 activity in participants with CAP, with and without depression, as well as healthy controls (no depression, no CAP). Root canal LPS levels were positively associated with CAP, clinical depression, severity of depression (as measured with the Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory) and O&NS biomarkers, especially NOx and TRAP. CAP-related depression was accompanied by increased levels of NOx, LOOH, AOPP, and TRAP. In CAP participants, there was a strong correlation (r = 0.734, p < 0.001) between root canal LPS and the HDRS score. There were significant and positive associations between CAP or root canal endotoxin with the vegetative and physio-somatic symptoms of the HDRS as well as a significant inverse association between root canal endotoxin and quality of life with strong effects on psychological, environmental, and social domains. It is concluded that increased root canal LPS accompanying CAP may cause depression and a lowered quality of life, which may be partly explained by activated O&NS pathways, especially NOx thereby enhancing hypernitrosylation and thus neuroprogressive processes. Dental health and "leaky teeth" may be intimately linked to the etiology and course of depression, while significantly impacting quality of life.

Metabolic syndrome components are associated with oxidative stress in overweight and obese patients

ABSTRACT Objective: The aim of this study is to evaluate the influence of the body mass index (BMI) and the metabolic syndrome (MetS) parameters on oxidative and nitrosative stress in overweight and obese subjects. Subjects and methods: Individuals were divided into three groups: the control group (G1, n = 131) with a BMI between 20 and 24.9 kg/m2, the overweight group (G2, n = 120) with a BMI between 25 and 29.9 kg/m2 and the obese group (G3, n = 79) with a BMI ≥ 30 kg/m2. Results: G3 presented higher advanced oxidation protein products (AOPPs) in relation to G1 and G2 (p = 0.001 and p = 0.011, respectively) whereas G2 and G3 had lower levels of nitric oxide (NO) (p = 0.009 and p = 0.048, respectively) compared to G1. Adjusted for the presence of MetS to evaluate its influence, the levels of AOPPs did not differ between the groups, whereas NO remained significantly lower. Data adjusted by the BMI showed that subjects with higher triacylglycerol levels had higher AOPPs (p = 0.001) and decreased total radical-trapping antioxidant parameter/uric Acid (p = 0.036). Subjects with lower high-density lipoprotein (HDL) levels and patients with higher blood pressure showed increased AOPPs (p = 0.001 and p = 0.034, respectively) and lower NO levels (p = 0.017 and p = 0.043, respectively). Subjects who presented insulin resistance had higher AOPPs (p = 0.024). Conclusions: Nitrosative stress was related to BMI, and protein oxidation and nitrosative stress were related to metabolic changes and hypertension. MetS components were essential participants in oxidative and nitrosative stress in overweight and obese subjects.

Hábitos nutricionais de adolescentes obesos envolvidos em um programa de orientação nutricional / Nutritional habits of obese adolescents involved in a nutritional program guidance

Objective: To assess the influence of nutritional guidelines on the food habits of overweight and obese adolescents. Methods: A cross-sectional study with 22 overweight or obese adolescents was conducted. The nutrition intervention program, in which adolescents received only guidelines covering topics on healthy eating, lasted twelve weeks. First, anthropometric measurements of weight and height were performedto verify the nutritional status. Subsequently, a food frequency questionnaire was applied through interviews. Dietary and anthropometric measurements were performed, before and after the program, to verify the influence of nutritional guidelines on the food habits of adolescents. Results: Regarding protein consumption, legumes, meat, and milk and dairy products were the groups where the nutritional guidelines were more effective, except for the milk and dairy products group. The group of fats and fried foods also improved percentage after nutritional guidance.The other food groups were not favorably influenced by nutritional guidance. Conclusion: Although the implementation of nutrition education focusing only on issues related to food had no effect in changing inappropriate eating habits, this study allowed a critical reflection about the ineffectiveness of isolated strategies and the possibility of changes in eating habits through nutritional guidance, based on the sum of strategies described in the literature.

Objetivo: Verificar a influência das orientações nutricionais sobre os hábitos alimentares dos adolescentes com sobrepeso e obesidade. Métodos: Foi realizado um estudo transversal com 22 adolescentes sobrepesos ou obesos. O programa de intervenção nutricional teve duração de 12 semanas, no qual os adolescentes recebiam somente orientações, abrangendo temas sobre alimentação saudável. Primeiramente, foram realizadas medidas antropométricas, para verificar o estado nutricional. Posteriormente, foi aplicado um questionário de frequência alimentar e um registro alimentar. As avaliações dietéticas e antropométricas foram realizadas antes e após o programa, para verificar a influência das orientações nutricionais sobre os hábitos alimentaresdos adolescentes. Resultados: Houve uma redução significativa no índicede massa corporal e no percentual de gordura, em ambos os sexos, no pós-programa; porém, esses indicativos ainda continuaram com valores elevados. Em relação ao consumo alimentar, o grupo das leguminosas e carnes foi o grupo no qual as orientações nutricionais foram mais efetivas, assim como o grupo das gorduras e frituras, em que houve uma redução no consumo após as orientações nutricionais. Os demais grupos alimentares não apresentaram resultados favoráveis. Conclusão: Apesar de a realização da educação nutricional com enfoque nos assuntos relacionados somente à alimentação não apresentar efeito na mudança dos hábitos alimentares inadequados, o presente estudo permitiu uma reflexão crítica sobre a ineficácia de estratégias isoladas e a possibilidade de mudanças nos hábitos alimentares por meio de orientação nutricional, a partir do somatório de estratégias descritas na literatura.

Trauma, sepse e desnutrição: um estudo de caso / Trauma, sepsis and malnutrition: a case study

A resposta orgânica ao estresse gerado pelo trauma tem como finalidade a restauração da homeostase. Os pacientes apresentam maior risco de desnutrição, o que os torna susceptíveis a infecções, devido ao estado de hipermetabolismo e hipercatabolismo que se encontram como consequência às respostas metabólicas à lesão. O presente estudo teve como objetivo avaliar o estado nutricional e a sua relação com a terapia nutricional enteral oferecida a um paciente hospitalizado com sequelas de trauma raquimedular e trauma crânio-encefálico, sepse de foco pulmonar, úlceras de pressão e desnutrido, para propor uma dieta que pudesse auxiliar no seu quadro clínico. A pesquisa apresentada refere-se a um estudo de caso de um paciente internado em março de 2010, sem previsão de alta hospitalar, em um hospital público da cidade de Londrina-PR. Foi realizado o acompanhamento nutricional, através da avaliação antropométrica, análise dos exames laboratoriais e avaliação da terapia nutricional enteral ofertada ao paciente. Conforme os resultados encontrados, foi proposta uma dieta que tivesse efeitos benéficos para a recuperação do paciente. Infelizmente a dieta proposta não foi iniciada a tempo de continuar o acompanhamento nutricional para avaliar a evolução do paciente.

The organic response to stress caused by trauma aims to restore homeostasis. Patients present increased risk of malnutrition, which makes them susceptible to infections due to the state of hypermetabolism and hypercatabolism as a result of the metabolic responses to injury. This study aimed to assess the nutritional status and its relation to enteral nutrition therapy provided to a hospitalized patient with sequelae of spinal cord injury and traumatic brain injury, pulmonary sepsis, pressure ulcers and malnutrition to offer a diet that could assist in his condition. This research refers to a case study of a patient hospitalized in a public hospital in the city of Londrina-PR in March 2010, with no forecast of hospital discharge. Nutritional monitoring was conducted through anthropometric assessment, laboratory analysis and evaluation of enteral nutrition therapy offered to the patient. As a result, a diet that could offer beneficial effects on patient recovery was proposed. Unfortunately dieting proposal was not started in time to continue monitoring to assess the nutritional outcomes.