The Relationship Between Metabolic Syndrome and Mortality Among Patients With Acute Respiratory Distress Syndrome in Acute Respiratory Distress Syndrome Network and Prevention and Early Treatment of Acute Lung Injury Network Trials.

OBJECTIVES: Metabolic syndrome is known to predict outcomes in COVID-19 acute respiratory distress syndrome (ARDS) but has never been studied in non-COVID-19 ARDS. We therefore aimed to determine the association of metabolic syndrome with mortality among ARDS trial subjects. DESIGN: Retrospective cohort study of ARDS trials' data. SETTING: An ancillary analysis was conducted using data from seven ARDS Network and Prevention and Early Treatment of Acute Lung Injury Network randomized trials within the Biologic Specimen and Data Repository Information Coordinating Center database. PATIENTS: Hospitalized patients with ARDS and metabolic syndrome (defined by obesity, diabetes, and hypertension) were compared with similar patients without metabolic syndrome (those with less than three criteria). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 28-day mortality. Among 4288 ARDS trial participants, 454 (10.6%) with metabolic syndrome were compared with 3834 controls (89.4%). In adjusted analyses, the metabolic syndrome group was associated with lower 28-day and 90-day mortality when compared with control (adjusted odds ratio [aOR], 0.70 [95% CI, 0.55-0.89] and 0.75 [95% CI, 0.60-0.95], respectively). With each additional metabolic criterion from 0 to 3, adjusted 28-day mortality was reduced by 18%, 22%, and 40%, respectively. In subgroup analyses stratifying by ARDS etiology, mortality was lower for metabolic syndrome vs. control in ARDS caused by sepsis or pneumonia (at 28 d, aOR 0.64 [95% CI, 0.48-0.84] and 90 d, aOR 0.69 [95% CI, 0.53-0.89]), but not in ARDS from noninfectious causes (at 28 d, aOR 1.18 [95% CI, 0.70-1.99] and 90 d, aOR 1.26 [95% CI, 0.77-2.06]). Interaction p = 0.04 and p = 0.02 for 28- and 90-day comparisons, respectively. CONCLUSIONS: Metabolic syndrome in ARDS was associated with a lower risk of mortality in non-COVID-19 ARDS. The relationship between metabolic inflammation and ARDS may provide a novel biological pathway to be explored in precision medicine-based trials.

COVID-19 infection characteristics and outcomes in a predominantly Latino community hospital.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has rapidly spread worldwide and claimed millions of lives. Several studies have attempted to understand the relationship between COVID-19 infection and health disparities. The aim of the current work was to evaluate the pre-admission health characteristics, symptomatology, diagnostic abnormalities, treatment measures and clinical outcomes of the community served by our institution, with a sub-analysis of our Hispanic community. Methods: This is a single-center, cross-sectional cohort study of patients with COVID-19 admitted from 15 March 2020 to 30 April 2020 to MacNeal Hospital. A retrospective chart review was performed including patients >18 years and a positive nasopharyngeal SARS-CoV-2 PCR. Demographical data, comorbidities, clinical data, treatment regimen, and patient outcomes were collected. Results: A total of 257 patients were included in the study of which 60.4% were identified as Hispanic. The median age at admission of Hispanic patients was significantly lower compared to non-Hispanic patients (56.6 vs. 65.7 years, p<0.01). Non-Hispanic patients had lower prevalence of hypertension, coronary artery disease, and chronic lung disease. Most common at presentation were shortness of breath (69.6%), cough (69.2%), and fever (64%). Hypertension was the most common comorbidity (53.6%). Approximately 89% of the patients received antibiotics, 40.4% hydroxy-chloroquine, 13.2% steroids, and 6% tocilizumab. Twenty six percent required mechanical ventilation (MV), and over half of them (56.7%) were Hispanic. The strongest factors associated with MV were smoking (OR 2.97, 95%CI 1.01-8.69), CRP >10 mg/dL (OR 4.53, 95%CI 1.49-13.38) and D-dimer >1.5 mcg/mL (OR 3.63, 95%CI 1.31-10.05). An oxygen saturation of >90% on room air on presentation was a protective factor when predicting intubation (OR 0.11, 95%CI 0.03-0.33). The overall 30-day mortality rate was 17.1% (n=44); 11.9% in the Hispanic group vs 26.3% in the non-Hispanic group (p<0.003). Conclusions: Our review of consecutive patients admitted with COVID-19 demonstrated that over half of patients were of Hispanic descent. Interestingly enough, despite being significantly younger and healthier, the need for mechanical ventilation in the Hispanic group was not significantly different compared to the non-Hispanic group. However, the Hispanic group had a lower mortality rate.

Sedation Usage in COVID-19 Acute Respiratory Distress Syndrome: A Multicenter Study.

BACKGROUND: Patients with COVID-19 acute respiratory distress syndrome (ARDS) have been shown to have high sedation requirements. OBJECTIVE: The purpose of this study was to compare sedative use between patients with COVID-19 ARDS and non-COVID-19 ARDS. METHODS: This was a retrospective study of patients with COVID-19 ARDS compared with historical controls of non-COVID-19 ARDS who were admitted to 2 hospitals from March 1, 2020, to April 30, 2020, and April 1, 2018, to December 31, 2019, respectively. The primary outcome was median cumulative dose of propofol (µg/kg) at 24 hours after intubation. RESULTS: There were 92 patients with COVID-19 ARDS and 37 patients with non-COVID-19 ARDS included. Within the first 24 hours of intubation, patients with COVID-19 ARDS required higher total median doses of propofol: 51 045 µg/kg (interquartile range, 26 150-62 365 µg/kg) versus 33 350 µg/kg (9632-51 455 µg/kg; P = 0.004). COVID-19 patients were more likely receive intravenous lorazepam (37% vs 14%; P = 0.02) and higher cumulative median doses of midazolam by days 5 (14 vs 4 mg; P = 0.04) and 7 of intubation (89 vs 4 mg; P = 0.03) to achieve the same median Richmond Analgesia-Sedation Scale scores. COVID-19 ARDS patients required more ventilator days (10 vs 6 days; P = 0.02). There was no difference in 30-day mortality. CONCLUSION AND RELEVANCE: Patients with COVID-19 ARDS required higher doses of propofol and benzodiazepines than patients with non-COVID-19 ARDS to achieve the same median levels of sedation.

Relación entre la capacidad de agencia de autocuidado y la calidad de vida en personas con insuficiencia cardiaca / Relationship Capacity of Self-Care Agency and Quality of Life in People with Heart Failure / Relação entre capacidade de agência do autocuidado e qualidade de vida em pessoas com insuficiência cardíaca

Introducción. La persona con insuficiencia cardiaca enfrenta cambios biopsicosociales que deterioran su calidad de vida. Es necesario conocer la relación existente entre el autocuidado y la calidad de vida, lo que puede orientar al profesional de enfermería en el diseño de intervenciones efectivas. Objetivo. Determinar la relación existente entre la capacidad de agencia de autocuidado y la calidad de vida relacionada con la salud en las personas con insuficiencia cardiaca, que son atendidas en el programa multidisciplinario de insuficiencia cardiaca en una institución de salud de cuarto nivel en Bogotá, Colombia. Método. Estudio descriptivo correlacional de corte transversal, realizado entre mayo y agosto de 2018; utilizando los instrumentos Appraisal of Self-care Agency Scale y el Cuestionario de Cardiomiopatía de Kansas City; la muestra correspondió a 107 pacientes, mayores de edad, con insuficiencia cardiaca estadio C y D. Resultados. La capacidad de agencia de autocuidado se encontró en categorías alta con 63,55% y muy alta con 34,57%; la calidad de vida relacionada con la salud se encontró preservada, con un puntaje general de 73,33; la relación existente entre las dos variables, según el coeficiente de correlación de Spearman, fue 0,316 con un valor p = 0,002, relación débil pero significativa. Conclusiones. Existe una relación entre las variables de interés, que se reafirma con las correlaciones significativas identificadas entre las dimensiones que las conforman. Estos hallazgos resaltan la pertinencia de abordar, en las intervenciones, temáticas que fortalezcan la capacidad de agencia de autocuidado, contribuyendo a mejorar la calidad de vida de estas personas.

Introduction. The person with heart failure faces biopsychosocial changes that impair their quality of life. It is necessary to know the relationship between self-care and quality of life, which can guide the nursing professional in the design of effective interventions. Objective. To determine the relationship between the capacity of self-care agency and health-related quality of life in people with heart failure who are treated in the multidisciplinary program of heart failure in a fourth level health institution in Bogotá, Colombia. Method. Descriptive study correlational, cross-sectional, made between May and August 2018; using the Appraisal of Self-care agency Scale Instruments and the Kansas City Cardiomyopathy Questionnaire; the sample corresponded to 107 patients, of legal age, with stage C and D heart failure. Results. The capacity of self-care agency was in high category with 63.55% and very high with 34.57%; the health-related quality of life was preserved, with an overall score of 73.33; the relationship between the two variables, according to the Spearman correlation coefficient, was 0.316 with a value p = 0.002, a weak but significant relationship. Conclusions. There is a relationship between the variables of interest, which is reaffirmed with the significant correlations identified between the dimensions that comprise them. These findings highlight the relevance of addressing, in the interventions, issues that strengthen the capacity of self-care agency, contributing to improve the quality of life of these people.

Introdução. A pessoa com insuficiência cardíaca enfrenta mudanças biopsicossociais deteriorando sua qualidade de vida. É preciso conhecer a relação existente entre autocuidado e qualidade de vida, o que pode nortear o profissional de enfermagem no desenho de intervenções eficazes. Objetivo. Determinar a relação entre a capacidade de agência de autocuidado e a qualidade de vida relacionada à saúde em pessoas com insuficiência cardíaca, tratadas no programa multidisciplinar de insuficiência cardíaca numa instituição de saúde de quarto nível em Bogotá, Colômbia. Método. Estudo descritivo correlacional transversal, realizado entre maio e agosto de 2018; utilizando os instrumentos Appraisal of Self-care Agency Scale e o Questionário de Cardiomiopatia de Kansas City; a amostra correspondeu a 107 pacientes, maiores de idade, com insuficiência cardíaca estagio C e D. Resultados. A capacidade de agência de autocuidado achou-se em categorias alta com 63,55% e muito alta com 34,57%; a qualidade de vida relacionada à saúde encontrou-se preservada, com escore geral de 73,33; a relação entre as duas variáveis, conforme o coeficiente de correlação de Spearman, foi 0,316 com valor p = 0,002, relação fraca, mas significativa. Conclusões. Existe relação entre as variáveis de interesse, o que se reafirma com as correlações significativas identificadas entre as dimensões que as compõem. Esses achados ressaltam a relevância de abordar, nas intervenções, questões que fortaleçam a capacidade de agência de autocuidado, contribuindo a melhorar a qualidade de vida dessas pessoas.

Relación agencia de autocuidado y calidad de vida en personas con insuficiencia cardiaca / Relationship between self-care agency and quality of life in people with heart failure

El presente estudio, de tipo cuantitativo correlacional, tiene como objetivo determinar la relación existente entre la capacidad de agencia de autocuidado y la calidad de vida relacionada con la salud en las personas con insuficiencia cardiaca que son atendidos en el programa multidisciplinario de insuficiencia cardiaca de una institución de salud de cuarto nivel en la ciudad de Bogotá, Colombia. La muestra correspondió a 107 pacientes. Las variables se midieron a través de los instrumentos Appraisal of self-care agency scale y el Cuestionario de cardiomiopatía de Kansas City. Resultados: La media de la edad fue 59.9 años, el 66.3% se encontró en la categoría de 51 a 75 años. El sexo masculino predominó con un 67.3%. La ocupación independiente obtuvo el mayor porcentaje. El nivel educativo fue 17.8% en bachillerato completo y universitario. La etiología más común fue isquémica con 40.18%. La clase funcional NYHA estuvo en clase I y II con 27.10% y 61.68% respectivamente. La FEVI fue <40% en el 84.11%. La capacidad de agencia de autocuidado se encontró en categorías alto con 63.55% y muy alto con 34.57%. La calidad de vida relacionada con la salud se encontró preservada, con un puntaje general de 73.33. La relación existente entre las dos variables (coeficiente de correlación de Spearman) fue 0.316 con un p=0.002, relación débil pero significativa. Los resultados del estudio ratifican la necesidad de generar propuestas de intervención de enfermería que evalúen estas variables y contribuyan a la atención integral de las personas con insuficiencia cardiaca.

The objective of this study, which is of a correlational quantitative, is to determine the relationship between self-care agency capacity and the quality of life related to health in people with heart failure who are treated in the multidisciplinary heart failure program of a fourth level health institution in the city of Bogotá, Colombia. The sample corresponded to 107 patients. The variables were measured through the Appraisal of self-care agency scale instruments and the Cardiomyopathy Questionnaire of Kansas City. Results: The mean age was 59.9 years, 66.3% was found in the category of 51 to 75 years. Male sex predominated with 67.3%. Independent occupation obtained the highest percentage. The educational level was 17.8% in high school and university. The most common etiology was ischemic with 40.18%. The NYHA functional class was in class I and II with 27.10% and 61.68% respectively. LVEF was < 40% in 84.11%. The self-care agency capacity was found in high categories with 63.55% and very high with 34.57%. The quality of life related to health was slightly affected with a general score of 73.33. The relationship between the two variables (Spearman correlation coefficient) was 0.316 with p = 0.002, a weak but significant relationship. The results of the study confirm the need to generate nursing intervention proposals that evaluate these variables and contribute to the comprehensive care of people with heart failure.

Tetrahydroisoquinolines affect the whole-cell phenotype of Mycobacterium tuberculosis by inhibiting the ATP-dependent MurE ligase.

OBJECTIVES: (S)-Leucoxine, isolated from the Colombian Lauraceae tree Rhodostemonodaphne crenaticupula Madriñan, was found to inhibit the growth of Mycobacterium tuberculosis H37Rv. A biomimetic approach for the chemical synthesis of a wide array of 1-substituted tetrahydroisoquinolines was undertaken with the aim of elucidating a common pharmacophore for these compounds with novel mode(s) of anti-TB action. METHODS: Biomimetic Pictet-Spengler or Bischler-Napieralski synthetic routes were employed followed by an evaluation of the biological activity of the synthesized compounds. RESULTS: In this work, the synthesized tetrahydroisoquinolines were found to inhibit the growth of M. tuberculosis H37Rv and affect its whole-cell phenotype as well as the activity of the ATP-dependent MurE ligase, a key enzyme involved in the early stage of cell wall peptidoglycan biosynthesis. CONCLUSIONS: As the correlation between the MIC and the half-inhibitory enzymatic concentration was not particularly strong, there is a credible possibility that these compounds have pleiotropic mechanism(s) of action in M. tuberculosis.

Superoxide anion production and expression of gp91(phox) and p47(phox) are increased in glomeruli and proximal tubules of cisplatin-treated rats.

The chemotherapeutic drug cisplatin has some side effects including nephrotoxicity that has been associated with reactive oxygen species production, particularly superoxide anion. The major source of superoxide anion is nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase. However, the specific segment of the nephron in which superoxide anion is produced has not been identified. Rats were sacrificed 72 h after cisplatin injection (7.5 mg/kg), and kidneys were obtained to isolate glomeruli and proximal and distal tubules. Cisplatin induced superoxide anion production in glomeruli and proximal tubules but not in distal tubules. This enhanced superoxide anion production was prevented by diphenylene iodonium, an inhibitor of NADPH oxidase. Consistently, this effect was associated with the increased expression of gp91(phox) and p47(phox), subunits of NADPH oxidase. The enhanced superoxide anion production in glomeruli and proximal tubules, associated with the increased expression of gp91(phox) and p47(phox), is involved in the oxidative stress in cisplatin-induced nephrotoxicity.

Aged garlic extract attenuates cerebral damage and cyclooxygenase-2 induction after ischemia and reperfusion in rats.

Different garlic products reduce the cerebral ischemic damage due to their antioxidant properties. In this work, we investigated the effect of aged garlic extract (AGE) on cyclooxygenase-2 (COX-2) protein levels and activity, and its role as a possible mechanism of neuroprotection in a cerebral ischemia model. Animals were subjected to 1 h of ischemia plus 24 h of reperfusion. AGE (1.2 ml/kg weight, i.p.) was administered at onset of reperfusion. To evaluate the damage induced by cerebral ischemia, the neurological deficit, the infarct area, and the histological alterations were measured. As an oxidative stress marker to deoxyribonucleic acid, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were determined. Finally, as inflammatory markers, TNFα levels and COX-2 protein levels and activity were measured. AGE treatment diminished the neurological alterations (61.6%), the infarct area (54.8%) and the histological damage (37.7%) induced by cerebral ischemia. AGE administration attenuated the increase in 8-OHdG levels (77.8%), in TNFα levels (76.6%), and in COX-2 protein levels (73.6%) and activity (30.7%) induced after 1 h of ischemia plus 24 h of reperfusion. These data suggest that the neuroprotective effect of AGE is associated not only to its antioxidant properties, but also with its capacity to diminish the increase in TNFα levels and COX-2 protein expression and activity. AGE may have the potential to attenuate the cerebral ischemia-induced inflammation.

Time-related changes in constitutive and inducible nitric oxide synthases in the rat striatum in a model of Huntington's disease.

Excitotoxicity and oxidative stress are mechanisms involved in the neuronal cell death induced by the intrastriatal injection of quinolinic acid (QUIN) as a model of Huntington's disease. Production of nitric oxide by nitric oxide synthase (NOS) has been proposed to participate in QUIN-induced neurotoxicity; however, the precise role of NOS in QUIN-induced toxicity still remains controversial. In order to provide further information on the role of NOS isoforms in QUIN toxicity, we performed real time RT-PCR and immunohistochemistry of inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal NOS (nNOS) and determined Ca(2+)-dependent and Ca(2+)-independent NOS activity in a temporal course (3-48h), after an intrastriatal injection of QUIN to rats. NOS isoforms exhibited a transitory expression of mRNA and protein after QUIN infusion: eNOS increased between 3 and 24h, iNOS between 12 and 24h, while nNOS at 35 and 48h. Ca(2+)-independent activity (iNOS) did not show any change, while Ca(2+)-dependent activity (constitutive NOS: eNOS/nNOS) exhibited increased levels at 3h. Our results support the participation of Ca(2+)-dependent NOS isoforms during the toxic events produced at early times after QUIN injection.

Poly(ADP-ribose) polymerase-1 is involved in the neuronal death induced by quinolinic acid in rats.

Reactive oxygen and nitrogen species formation leads to DNA damage in animals treated with quinolinic acid. Poly(ADP-ribose) polymerase-1 (PARP-1) is a protein involved in the DNA base excision repair system. Its overactivation promotes cellular energy deficit and necrosis. Here, we evaluated the effect of PJ-34, a potent inhibitor of PARP-1, on the neuronal damage induced by quinolinic acid. Animals were administered with PJ-34 (10 mg/kg, i.p.), 1 h before and 1 h after a striatal infusion of 1 microl of quinolinic acid (240 nmol). PJ-34 clearly attenuated the circling behavior produced by quinolinic acid and completely prevented the histological damage induced by the toxin. The protective effect of PJ-34 suggests that PARP-1 activation is playing an active role in the neuronal death induced by quinolinic acid.

S-allylcysteine scavenges singlet oxygen and hypochlorous acid and protects LLC-PK(1) cells of potassium dichromate-induced toxicity.

It has been found that S-allylcysteine (SAC), a garlic-derived compound, has in vivo and in vitro antioxidant properties. In addition, it is known that SAC is able to scavenge different reactive oxygen or nitrogen species including superoxide anion (O(2)(-)), hydrogen peroxide (H(2)O(2)), hydroxyl radical (OH()), and peroxynitrite anion (ONOO(-)) although the IC(5O) values for each reactive species has not been calculated and the potential ability of SAC to scavenge singlet oxygen ((1)O(2)) and hypochlorous acid (HOCl) has not been explored. The purposes of this work was (a) to explore the potential ability of SAC to scavenge (1)O(2) and HOCl, (b) to further characterize the O(2)(-), H(2)O(2), OH(), and ONOO(-) scavenging ability of SAC by measuring the IC(50) values using in vitro assays, and (c) to explore the potential ability of SAC to ameliorate the potassium dichromate (K(2)Cr(2)O(7))-induced cytotoxicity in LLC-PK1 cells in which oxidative stress is involved. The scavenging activity was compared against the following reference compounds: N-acetylcysteine for O(2)(-), sodium pyruvate for H(2)O(2), dimethylthiourea for OH(), lipoic acid and glutathione for (1)O(2), lipoic acid for HOCl, and penicillamine for ONOO(-). It was found that SAC was able to scavenge concentration-dependently all the species assayed with the following IC(5O) (mean+/-SEM, mM): O(2)(-) (14.49+/-1.67), H(2)O(2) (68+/-1.92), OH() (0.68+/-0.06), (1)O(2) (1.93+/-0.27), HOCl (2.86+/-0.15), and ONOO(-) (0.80+/-0.05). When the ability of SAC to scavenge these species was compared to those of the reference compounds it was found that the efficacy of SAC (a) to scavenge O(2)(-), H(2)O(2), OH(), and ONOO(-) was lower, (b) to scavenge HOCl was similar, and (c) to scavenge (1)O(2) was higher. In addition, it was found that SAC was able to prevent K(2)Cr(2)O(7)-induced toxicity in LLC-PK1 cells in culture. It was showed for the first time that SAC is able to scavenge (1)O(2) and HOCl and to ameliorate the K(2)Cr(2)O(7)-induced toxicity.

Medio familiar y entorno escolar: detonantes y antídotos de las conductas agresivas en niños en edad escolar / Medio familiar y entorno escolar: detonantes y antídotos de las conductas agresivas en niños en edad escolar

Se realizó una investigación-acción participativa en 32 niños en edad escolar, con conductas agresivas, del Colegio General Santander de Chía, para observar cómo influye el medio familiar y escolar en las conductas agresivas de los niños, y plantear alternativas para modular dichas conductas. El estudio indagó, en niños y padres de familia, factores determinantes de las conductas agresivas. Se evaluaron el tipo de estructura familiar, las personas responsables del cuidado de los niños, las condiciones de vivienda, el hacinamiento, el nivel de escolaridad, la situación laboral, los métodos correctivos y el consumo de alcohol por parte de los padres o cuidadores, como variables determinantes del medio familiar. Se encontró que los determinantes que influyeron en las manifestaciones agresivas de los niños, en este caso, fueron: el tipo de estructura familiar, el bajo nivel de escolaridad de los padres, y las personas responsables de la educación y cuidado de los niños; y en relación con el medio escolar, la fuente de imitación de conductas agresivas.

Aged garlic extract induces proliferation and ameliorates gentamicin-induced toxicity in LLC-PK1 cells.

Gentamicin (GM)-induced nephrotoxicity limits the use of this antibiotic. It has been shown that aged garlic extract (AGE) and S-allylcysteine (SAC), the most abundant organosulfur compound in AGE, ameliorate GM-induced nephrotoxicity in rats. The present communication evaluated the effect of AGE and SAC on proliferation and on GM-induced toxicity and genotoxicity of porcine kidney epithelial cell line (LLC-PK1 cells). The cells were preincubated with different concentrations of AGE or SAC for 12 h before incubation with 8 mm GM for an additional 72 h. At the end of this time, cell viability, genotoxicity and proliferation were evaluated. AGE stimulated cell proliferation and protected LLC-PK1 cells from GM-mediated toxicity and genotoxicity. SAC partially prevented only GM-induced genotoxicity. These results suggest that the stimulation of cell proliferation could possibly be one of the mechanisms involved in the in vitro protective effect of AGE in GM-induced toxicity of LLC-PK1 cells.

Medio familiar y entorno escolar: detoantes y antídotos de las conductas agresivas en niños en edad escolar / Average relative and scholastic surroundings: detonating and antidotes of the aggressive conducts in children in scholastic age

Se realizó una investigación-acción participativa en 32 niños en edad escolar, con conductas agresivas, del Colegio General Santander de Chía, para observar cómo influye el medio familiar y escolar en las conductas agresivas de los niños, y plantear alternativas para modular dichas conductas. El estudio indagó, en niños y padres de familia, factores determinantes de las conductas agresivas. Se evaluaron el tipo de estructura familiar, las personas responsables del cuidado de los niños, las condiciones de vivienda, el hacinamiento, el nivel de escolaridad, la situación laboral, los métodos correctivos y el consumo de alcohol por parte de los padres o cuidadores, como variables determinantes del medio familiar. Se encontró que los determinantes que influyeron en las manifestaciones agresivas de los niños, en este caso, fueron: el tipo de estructura familiar, el bajo nivel de escolaridad de los padres, y las personas responsables de la educación y cuidado de los niños; y en relación con el medio escolar, la fuente de imitación de conductas agresivas

Hypothyroidism attenuates protein tyrosine nitration, oxidative stress and renal damage induced by ischemia and reperfusion: effect unrelated to antioxidant enzymes activities.

BACKGROUND: It has been established that hypothyroidism protects rats against renal ischemia and reperfusion (IR) oxidative damage. However, it is not clear if hypothyroidism is able to prevent protein tyrosine nitration, an index of nitrosative stress, induced by IR or if antioxidant enzymes have involved in this protective effect. In this work it was explored if hypothyroidism is able to prevent the increase in nitrosative and oxidative stress induced by IR. In addition the activity of the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase was studied. Control and thyroidectomized (HTX) rats were studied 24 h of reperfusion after 60 min ischemia. METHODS: Male Wistar rats weighing 380 +/- 22 g were subjected to surgical thyroidectomy. Rats were studied 15 days after surgery. Euthyroid sham-operated rats were used as controls (CT). Both groups of rats underwent a right kidney nephrectomy and suffered a 60 min left renal ischemia with 24 h of reperfusion. Rats were divided in four groups: CT, HTX, IR and HTX+IR. Rats were sacrificed and samples of plasma and kidney were obtained. Blood urea nitrogen (BUN) and creatinine were measured in blood plasma. Kidney damage was evaluated by histological analysis. Oxidative stress was measured by immunohistochemical localization of protein carbonyls and 4-hydroxy-2-nonenal modified proteins. The protein carbonyl content was measured using antibodies against dinitrophenol (DNP)-modified proteins. Nitrosative stress was measured by immunohistochemical analysis of 3-nitrotyrosine modified proteins. The activity of the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase was measured by spectrophotometric methods. Multiple comparisons were performed with ANOVA followed by Bonferroni t test. RESULTS: The histological damage and the rise in plasma creatinine and BUN induced by IR were significantly lower in HTX+IR group. The increase in protein carbonyls and in 3-nitrotyrosine and 4-hydroxy-2-nonenal modified proteins was prevented in HTX+IR group. IR-induced decrease in renal antioxidant enzymes was essentially not prevented by HTX in HTX+IR group. CONCLUSION: Hypothyroidism was able to prevent not only oxidative but also nitrosative stress induced by IR. In addition, the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase seem not to play a protective role in this experimental model.

Time course study of oxidative and nitrosative stress and antioxidant enzymes in K2Cr2O7-induced nephrotoxicity.

BACKGROUND: Potassium dichromate (K2Cr2O7)-induced nephrotoxicity is associated with oxidative and nitrosative stress. In this study we investigated the relation between the time course of the oxidative and nitrosative stress with kidney damage and alterations in the following antioxidant enzymes: Cu, Zn superoxide dismutase (Cu, Zn-SOD), Mn-SOD, glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT). METHODS: Nephrotoxicity was induced in rats by a single injection of K2Cr2O7. Groups of animals were sacrificed on days 1,2,3,4,6,8,10, and 12. Nephrotoxicity was evaluated by histological studies and by measuring creatinine clearance, serum creatinine, blood urea nitrogen (BUN), and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and total protein. Oxidative and nitrosative stress were measured by immunohistochemical localization of protein carbonyls and 3-nitrotyrosine, respectively. Cu, Zn-SOD, Mn-SOD, and CAT were studied by immunohistochemical localization. The activity of total SOD, CAT, GPx, and GR was also measured as well as serum and kidney content of chromium and urinary excretion of NO2 -/NO3-. Data were compared by two-way analysis of variance followed by a post hoc test. RESULTS: Serum and kidney chromium content increased reaching the highest value on day 1. Nephrotoxicity was made evident by the decrease in creatinine clearance (days 1-4) and by the increase in serum creatinine (days 1-4), BUN (days 1-6), urinary excretion of NAG (days 1-4), and total protein (day 1-6) and by the structural damage to the proximal tubules (days 1-6). Oxidative and nitrosative stress were clearly evident on days 1-8. Urinary excretion of NO2-/NO3- decreased on days 2-6. Mn-SOD and Cu, Zn-SOD, estimated by immunohistochemistry, and total SOD activity remained unchanged. Activity of GPx decreased on days 3-12 and those of GR and CAT on days 2-10. Similar findings were observed by immunohistochemistry of CAT. CONCLUSION: These data show the association between oxidative and nitrosative stress with functional and structural renal damage induced by K2Cr2O7. Renal antioxidant enzymes were regulated differentially and were not closely associated with oxidative or nitrosative stress or with kidney damage. In addition, the decrease in the urinary excretion of NO2-/NO3- was associated with the renal nitrosative stress suggesting that nitric oxide was derived to the formation of reactive nitrogen species involved in protein nitration.

S-allylmercaptocysteine scavenges hydroxyl radical and singlet oxygen in vitro and attenuates gentamicin-induced oxidative and nitrosative stress and renal damage in vivo.

BACKGROUND: Oxidative and nitrosative stress have been involved in gentamicin-induced nephrotoxicity. The purpose of this work was to study the effect of S-allylmercaptocysteine, a garlic derived compound, on gentamicin-induced oxidative and nitrosative stress and nephrotoxicity. In addition, the in vitro reactive oxygen species scavenging properties of S-allylmercaptocysteine were studied. RESULTS: S-allylmercaptocysteine was able to scavenge hydroxyl radicals and singlet oxygen in vitro. In rats treated with gentamicin (70 mg/Kg body weight, subcutaneously, every 12 h, for 4 days), renal oxidative stress was made evident by the increase in protein carbonyl content and 4-hydroxy-2-nonenal, and the nitrosative stress was made evident by the increase in 3-nitrotyrosine. In addition, gentamicin-induced nephrotoxicity was evident by the: (1) decrease in creatinine clearance and in activity of circulating glutathione peroxidase, and (2) increase in urinary excretion of N-acetyl-beta-D-glucosaminidase, and (3) necrosis of proximal tubular cells. Gentamicin-induced oxidative and nitrosative stress and nephrotoxicity were attenuated by S-allylmercaptocysteine treatment (100 mg/Kg body weight, intragastrically, 24 h before the first dose of gentamicin and 50 mg/Kg body weight, intragastrically, every 12 h, for 4 days along gentamicin-treatment). CONCLUSION: In conclusion, S-allylmercaptocysteine is able to scavenge hydroxyl radicals and singlet oxygen in vitro and to ameliorate the gentamicin-induced nephrotoxicity and oxidative and nitrosative stress in vivo.

Soy protein diet ameliorates renal nitrotyrosine formation and chronic nephropathy induced by puromycin aminonucleoside.

It has been shown that reactive oxygen species are involved in chronic puromycin aminonucleoside (PAN) induced nephrotic syndrome (NS) and that a 20% soy protein diet reduces renal damage in this experimental model. The purpose of the present work was to investigate if a 20% soy protein diet is able to modulate kidney nitrotyrosine formation and the activity of renal antioxidant enzymes (catalase, glutathione peroxidase, Cu,Zn- or Mn-superoxide dismutase) which could explain, at least in part, the protective effect of the soy protein diet in rats with chronic NS induced by PAN. Four groups of rats were studied: (1) Control rats fed 20% casein diet, (2) Nephrotic rats fed 20% casein diet, (3) Control rats fed 20% soy protein diet, and (4) Nephrotic rats fed 20% soy protein diet. Chronic NS was induced by repeated injections of PAN and rats were sacrificed at week nine. The soy protein diet ameliorated proteinuria, hypercholesterolemia, and the increase in serum creatinine and blood urea nitrogen observed in nephrotic rats fed 20% casein diet. Kidney nitrotyrosine formation increased in nephrotic rats fed 20% casein diet and this increase was ameliorated in nephrotic rats fed 20% soy protein diet. However, the soy protein diet was unable to modulate the antioxidant enzymes activities in control and nephrotic rats fed 20% soy protein diet. Food intake was similar in the two diet groups. The protective effect of a 20% soy protein diet on renal damage in chronic nephropathy induced by PAN was associated with the amelioration in the renal nitrotyrosine formation but not with the modulation of antioxidant enzymes.

Protective effect of diallyl sulfide on oxidative stress and nephrotoxicity induced by gentamicin in rats.

Gentamicin (GM) is an antibiotic whose clinical use is limited by its nephrotoxicity. Experimental evidences suggest a role of reactive oxygen species in GM-induced nephrotoxicity. In this work we explored the effect of diallyl sulfide (DAS), a garlic-derived compound with antioxidant properties, on GM-induced nephrotoxicity. Four groups of rats were studied: (1) Control, treated intragastrically with olive oil as a vehicle, (2) GM, treated subcutaneously with GM (125 mg/kg/day for 4 days), (3) DAS, treated intragastrically with DAS (50 mg/kg/day for 4 days), and (4) GM + DAS. Nephrotoxicity was made evident by: (1) the increase in creatinine and blood urea nitrogen in serum, (2) the increase in urinary excretion of N-acetyl-beta-D-glucosaminidase and total protein, and (3) necrosis of proximal tubular cells. These functional and structural alterations were prevented or ameliorated by DAS treatment. In addition, GM increased levels of renal oxidative stress markers nitrotyrosine and protein carbonyl groups which were also ameliorated by DAS in GM + DAS group. The mechanism by which DAS has a protective effect on GM-induced nephrotoxicity may be related, at least in part, to the decrease in oxidative stress in renal cortex.