Caracterización clínica y epidemiológica de los pacientes con hepatitis alcohólica en el Hospital Regional de Talca: estudio retrospectivo de 5 años (2017-2022) / Clinical and epidemiological characterisation of patients with alcoholic hepatitis in the Regional Hospital of Talca - 5-year retrospective study (2017-2022)

Alcoholic Hepatitis (HA) represent to one of the pathological entities in the context of liver damage associated with excessive and prolonged alcohol consumption. Despite its high mortality, making the early diagnosis is still a challenge for physicians. The local information of this pathology is limited, so this work consists of conducting a retrospective study on the clinical and epidemiological characteristics of patients diagnosed with HA at the Regional Hospital of Talca (HRT); in order to make available to the treating doctors, the greatest amount of data contributing to decision-making for the benefit of patients. Methods: The clinical records of all patients discharged from the HRT with a diagnosis of HA during the period between January 2017 and August 2022 were reviewed. Background information such as: chief complaint, main symptoms, comorbidities, laboratory tests, treatment, evolution and survival, etc., was collected for analysis and to obtain the conclusions presented. Results: A total of 16 patients were studied; 93.75 % were male and 6.24 % female; with a mean age of 52. Of the patients, 87.5 % had a history of DHC. All had alcohol abuse for more than 5 years and 93.75% had active alcoholism. The most frequent laboratory findings included hyperbilirubinaemia (93.75 %), GOT/GPT ratio >2 (50 %) and leukocytosis (56.25 %). Of the total patients studied, 68.75% had a survival of more than 1 year after the event, while 12.5% died during hospitalisation.

Quantification of mitochondrial DNA damage and copy number in circulating blood of patients with systemic sclerosis by a qPCR-based assay

Abstract Background: Although not fully understood, oxidative stress has been implicated in the pathogenesis of different autoimmune diseases such as systemic sclerosis. Accumulating evidence indicates that oxidative stress can induce mitochondrial DNA (mtDNA) damage and variations in mtDNA copy number (mtDNAcn). Objective: The aim of this study was to explore mtDNAcn and oxidative DNA damage byproducts in peripheral blood of patients with systemic sclerosis and healthy controls. Methods: Forty six patients with systemic sclerosis and forty nine healthy subjects were studied. Quantitative real-time PCR used to measure the relative mtDNAcn and the oxidative damage (oxidized purines) of each sample. Results: The mean mtDNAcn was lower in patients with systemic sclerosis than in healthy controls whereas the degree of mtDNA damage was significantly higher in cases as compared to controls. Moreover, there was a negative correlation between mtDNAcn and oxidative DNA damage. Study limitations: The lack of simultaneous analysis and quantification of DNA oxidative damage markers in serum or urine of patients with systemic sclerosis and healthy controls. Conclusion: These data suggest that alteration in mtDNAcn and increased oxidative DNA damage may be involved in the pathogenesis of systemic sclerosis.

Increased levels of reactive oxygen species in platelets and platelet-derived microparticles and the risk of respiratory failure in HIV/AIDS patients

Respiratory failure (RF) is the main cause of hospital admission in HIV/AIDS patients. This study assessed comorbidities and laboratory parameters in HIV/AIDS inpatients with RF (N = 58) in relation to those without RF (N = 36). Tuberculosis showed a huge relative risk and platelet counts were slightly higher in HIV/AIDS inpatients with RF. A flow cytometry assay for reactive oxygen species (ROS) showed lower levels in platelets of these patients in relation to the healthy subjects. However, when stimulated with adrenaline, ROS levels increased in platelets and platelet-derived microparticles of HIV/AIDS inpatients, which may increase the risk of RF during HIV and tuberculosis (HIV-TB) coinfection.

Increased ROS production and DNA damage in monocytes are biomarkers of aging and atherosclerosis

BACKGROUND: New evidence demonstrates that aging and dyslipidemia are closely associated with oxidative stress, DNA damage and apoptosis in some cells and extravascular tissues. However, in monocytes, which are naturally involved in progression and/or resolution of plaque in atherosclerosis, this concurrence has not yet been fully investigated. In this study, we evaluated the influence of aging and hypercholesterolemia on serum pro-inflammatory cytokines, oxidative stress, DNA damage and apoptosis in monocytes from apolipoprotein E-deficient (apoE-/-) mice compared with age-matched wild-type C57BL/6 (WT) mice. Experiments were performed in young (2-months) and in old (18-months) male wild-type (WT) and apoE-/- mice. RESULTS: Besides the expected differences in serum lipid profile and plaque formation, we observed that atherosclerotic mice exhibited a significant increase in monocytosis and in serum levels of pro-inflammatory cytokines compared to WT mice. Moreover, it was observed that the overproduction of ROS, led to an increased DNA fragmentation and, consequently, apoptosis in monocytes from normocholesterolemic old mice, which was aggravated in age-matched atherosclerotic mice. CONCLUSIONS: In this study, we demonstrate that a pro-inflammatory systemic status is associated with an impairment of functionality of monocytes during aging and that these parameters are fundamental extra-arterial contributors to the aggravation of atherosclerosis. The present data open new avenues for the development of future strategies with the purpose of treating atherosclerosis.

Obesity, bariatric surgery and oxidative stress / Obesidade, cirurgia bariátrica e estresse oxidativo

Summary Introduction: Obesity refers to the accumulation of fatty tissues and it favors the occurrence of oxidative stress. Alternatives that can contribute to body weight reduction have been investigated in order to reduce the production of reactive oxygen species responsible for tissue damage. The aim of the current study was to assess whether the oxidant and antioxidant markers of obese women before and after bariatric surgery were able to reduce oxidative damage. Method: We have assessed 16 morbidly obese women five days before and 180 days after the surgery. The control group comprised 16 non-obese women. Levels of thiobarbituric acid-reactive substances, carbonylated proteins, reduced glutathione and ascorbic acid were assessed in the patients' plasma. Results: Levels of lipid peroxidation and protein carbonylation in the pre-surgical obese women were higher than those of the controls and post-surgical obese women. Levels of reduced glutathione in the pre-surgical obese women were high compared to the controls, and declined after surgery. Levels of ascorbic acid fell in the pre--surgical obese women compared to the control and post-surgical obese women. Conclusion: Body weight influences the production of reactive oxygen species. Bariatric surgery, combined with weight loss and vitamin supplementation, reduces cellular oxidation, thus reducing tissue damage.

Resumo Introdução: Na obesidade, verifica-se um acúmulo de tecido adiposo, o que favorece a ocorrência de estresse oxidativo. A fim de diminuir a produção das espécies reativas que levam a danos teciduais, buscam-se alternativas que contribuam para a redução do peso corporal. Este estudo avaliou se os marcadores oxidantes e antioxidantes de obesas antes e após cirurgia bariátrica reduziram o dano oxidativo. Método: Foram avaliadas 16 mulheres obesas mórbidas cinco dias antes e 180 dias após o procedimento cirúrgico. O grupo controle constituiu-se de 16 mulheres não obesas. Os níveis das substâncias reativas ao ácido tiobarbitúrico, das proteínas carboniladas, da glutationa reduzida e do ácido ascórbico foram avaliados no plasma dessas pacientes. Resultados: Os níveis de lipoperoxidação e da carbonilação de proteínas nas obesas pré-cirúrgicas eram mais elevados quando comparados ao controle e às obesas pós-cirúrgicas; os níveis de glutationa reduzida eram maiores nas obesas pré-cirúrgicas em comparação ao controle e diminuíram após a cirurgia; os níveis de ácido ascórbico eram menores nas obesas pré-cirúrgicas em relação ao controle e às obesas pós-cirúrgicas. Conclusão: Observou-se que a massa corporal influenciou na produção das espécies reativas. A cirurgia bariátrica, somada à perda de peso e à suplementação vitamínica, diminui a oxidação celular e, com isso, reduz os danos teciduais.

Oxidative stress in sepsis. Possible production of free radicals through an erythrocyte-mediated positive feedback mechanism

Abstract Background: Sepsis is an illness with a high morbidity for which no effective treatment exists. Its treatment has a high cost because it usually requires an intensive care unit and expensive antibiotics. The present study focus in the production of reactive oxygen species in the early stages of sepsis. This study aimed at investigating the production of reactive oxygen specie during the inflammatory response in patients with sepsis. Methods: Reactive oxygen specie production and insoluble myeloperoxidase obtained from fresh whole blood were measured by photon counting chemiluminescence in the blood of 18 septic patients and 12 healthy individuals. Modified red blood cells were evaluated by staining of blood smears. The production of reactive oxygen species by macrophages and polymorphonuclear leukocytes put into contact with modified red blood cells were also assessed by photon counting chemiluminescence. Results: The appearance of oxidatively modified erythrocytes, which is an evidence of oxidative stress, was supported by the detection of reactive oxygen species and insoluble myeloperoxidase in the whole blood of all septic patients. Peroxynitrite was the main reactive oxygen species found in the whole blood. Oxidatively modified erythrocytes activated phagocytic cells in vitro, leading to the considerable production of free radicals. Conclusion: It was found that sepsis led to a high oxidative stress and to extensive modification of erythrocytes. It is proposed that a positive feedback mechanism, involving the activation of circulating leukocytes by these modified erythrocytes would maintain the pro-oxidative state even after the disappearance of bacteria.

Erythrocyte oxidative stress markers in children with sickle cell disease / Marcadores de estresse oxidativo em eritrócitos de crianças com doença falciforme

Abstract Objective To determine eight parameters of oxidative stress markers in erythrocytes from children with sickle cell disease and compare with the same parameters in erythrocytes from healthy children, since oxidative stress plays an important role in the pathophysiology of sickle cell disease and because this disease is a serious public health problem in many countries. Methods Blood samples were obtained from 45 children with sickle cell disease (21 males and 24 females with a mean age of 9 years; range: 3–13 years) and 280 blood samples were obtained from children without hemoglobinopathies (137 males and 143 females with a mean age of 10 years; range: 8–11 years), as a control group. All blood samples were analyzed for methemoglobin, reduced glutathione, thiobarbituric acid reactive substances, percentage of hemolysis, reactive oxygen species, and activity of the enzymes glucose 6-phosphate dehydrogenase, superoxide dismutase, and catalase. Data were analyzed using Student's t-test and were expressed as the mean ± standard deviation. A p-value of <0.05 was considered significant. Results Significant differences were observed between children with sickle cell disease and the control group for the parameters methemoglobin, thiobarbituric acid reactive substances, hemolysis, glucose 6-phosphate dehydrogenase activity, and reactive oxygen species, with higher levels in the patients than in the controls. Conclusions Oxidative stress parameters in children's erythrocytes were determined using simple laboratory methods with small volumes of blood; these biomarkers can be useful to evaluate disease progression and outcomes in patients.

Resumo Objetivo Determinar parâmetros de estresse oxidativo em eritrócitos de crianças com doença falciforme e compará-los com os mesmos parâmetros em eritrócitos de crianças saudáveis, pois o estresse oxidativo desempenha um importante papel na fisiopatologia da doença falciforme, considerada um sério problema de saúde pública em muitos países. Métodos Foram obtidas amostras de sangue de 45 crianças com doença falciforme (21 meninos e 24 meninas com média de 9 anos, variação de 3 a 13) e 280 amostras de sangue de crianças sem hemoglobinopatias (137 meninos e 143 meninas com média de 10 anos, variação de 8 a 11), como grupo controle. Em todas as amostras foram determinados meta-hemoglobina, glutationa reduzida, substâncias reativas ao ácido tiobarbitúrico, porcentagem de hemólise, espécies reativas de oxigênio e atividade das enzimas glucose6-fosfato desidrogenase, superóxido dismutase e catalase. Os dados foram analisados com o teste t de Student e foram expressos como média ± desvio padrão. Um valor de p < 0,05 foi considerado significativo. Resultados Foram observadas diferenças significativas entre as crianças com doença falciforme e o grupo controle para os parâmetros meta-hemoglobina, substâncias reativas ao ácido tiobarbitúrico, porcentagem de hemólise, espécies reativas de oxigênio e atividade da enzima glucose6-fosfato desidrogenase, com níveis aumentados nos pacientes. Conclusões Foi possível determinar parâmetros de estresse oxidativo em eritrócitos de crianças, com técnicas laboratoriais simples e pequenos volumes de sangue. Esses biomarcadores podem ser úteis na avaliação da progressão e dos resultados de tratamentos da doença.

O impacto da fibrose cística no perfil imunológico de pacientes pediátricos / The impact of cystic fibrosis on the immunologic profile of pediatric patients

OBJETIVO: Comparar o estado imunológico de 44 pacientes pediátricos com fibrose cística (FC)a umgrupo-controle formado por 16 indivíduos saudáveis. MÉTODOS: Foram selecionados para o estudo pacientes com FC com idade entre 3 e 12 anos, apresentando um escore clínico moderado e bom. Foram avaliados a glutationa eritrocitária, a produção de espécies reativas de oxigênio, citocinas (TNF-α, IFN-γ, IL-8, IL-6, IL-10) em culturas de células mononucleares do sangue periférico em condições espontâneas e estimuladas por BCG ou PHA, a concentração sérica de TGF-β2, IgA, IgG, IgM, IgE e IgA salivar. RESULTADOS :A produção espontânea de TNF-α, IL-6 e IL-10, a produção de IL-6 estimulada por PHA e TGF-β2, IgA e IgG séricas aumentaram em amostras de pacientes com FC. Indivíduos saudáveis tiveram uma produção mais elevada de TNF-α em resposta a BCG. CONCLUSÃO: Apesar de os pacientes com FC parecerem clinicamente estáveis, os resultados de seus exames de sangue periférico mostraram que houve um impacto sobre o sistema imunológico.

OBJECTIVE: To compare the immunologic state of 44 pediatric patients with cystic fibrosis (CF) with a control group consisting of 16 healthy individuals. METHODS: CF patients aged 3 to 12 years with moderate to good clinical score were selected for the study. Erythrocytic glutathione, production of reactive oxygen species, cytokines (TNF-α, IFN-γ, IL-8, IL-6, IL-10) in peripheral blood mononuclear cells cultures under spontaneous and BCG- or PHA-stimulated conditions, serum concentrations of TGF-β2, IgA, IgG, IgM, IgE, and salivary IgA were evaluated. RESULTS: The spontaneous production of TNF-α, IL-6, and IL-10, the PHA-stimulated production of IL-6, and the serum TGF-β2, IgA, and IgG were increased in samples from CF patients. Healthy subjects had a higher production of TNF-α in response to BCG. CONCLUSION: Although CF patients appearedclinically stable, the results of their peripheral blood examinations demonstrated an impact on the immune system.

Acute effects of resistance exercise and intermittent intense aerobic exercise on blood cell count and oxidative stress in trained middle-aged women

The aim of this study was to compare the effect of an intermittent intense aerobic exercise session and a resistance exercise session on blood cell counts and oxidative stress parameters in middle-aged women. Thirty-four women were selected and divided into three groups: RE group (performing 60 min of resistance exercises, N = 12), spinning group (performing 60 min of spinning, N = 12), and control group (not exercising regularly, N = 10). In both exercise groups, lymphocytes and monocytes decreased after 1-h recuperation (post-exercise) compared to immediately after exercise (P < 0.05). Immediately after exercise, in both exercised groups, a significant increase in TBARS (from 16.5 ± 2 to 25 ± 2 for the spinning group and from 18.6 ± 1 to 28.2 ± 3 nmol MDA/mL serum for the RE group) and protein carbonyl (from 1.0 ± 0.3 to 1.6 ± 0.2 for the spinning group and from 0.9 ± 0.2 to 1.5 ± 0.2 nmol/mg protein for the RE group) was observed (P < 0.05). A decrease in antioxidant activities (non-protein sulfhydryl, superoxide dismutase, catalase) was also demonstrated with a negative correlation between damage markers and antioxidant body defenses (P < 0.05). These results indicate that an acute bout of intermittent or anaerobic exercise induces immune suppression and increases the production of reactive oxygen species, causing oxidative stress in middle-aged and trained women. Furthermore, we demonstrated that trained women show improved antioxidant capacity and lower oxidative damage than sedentary ones, demonstrating the benefits of chronic regular physical activity.

Oxidative stress and interleukin-6 secretion during the progression of type 1 diabetes / Estresse oxidativo e secreção de interleucina-6 durante a progressão do diabetes tipo 1

OBJECTIVE: To evaluate inflammatory, oxidizing, and reducing responses during the progression of type 1 diabetes mellitus (T1DM) in patients without chronic complications. SUBJECTS AND METHODS: Plasma antioxidant status, reactive oxygen species (ROS), and interleukin-6 (IL-6) were measured in 42 patients with T1DM and in 24 healthy subjects. RESULTS: Significant increases were detected in the median values of ROS and IL-6 in patients with T1DM compared with healthy subjects (ROS ~ 4,836 vs. 2,036 RLU/min, respectively; P < .05: IL-6 ~ 14.2 vs. 9.7 pg/mL, respectively; P = .002). No significant between-group differences (P > 0.05) were observed in oxidizing responses or in IL-6 concentrations when diabetic patients were grouped according to time after diagnosis (0 - 10, 10 - 20 and > 20 years). Plasma antioxidant responses were similar in patients with T1DM and in healthy subjects. CONCLUSIONS: Our results demonstrate that oxidizing and inflammatory responses are increased at the onset of T1DM, but remain unchanged during disease progression. These findings suggest that functional changes involved in diabetic complications may commence in the first years after diagnosis.

OBJETIVO: Avaliar as respostas inflamatória, oxidativa e redutora na progressão do diabetes melito tipo 1 (DM1) em pacientes sem complicações crônicas. SUJEITOS E MÉTODOS: Capacidade antioxidante do plasma, espécies reativas de oxigênio (ROS) e interleucina-6 (IL-6) foram avaliadas em 42 pacientes com DM1 e 24 indivíduos saudáveis. RESULTADOS: Aumentos significativos foram detectados nas medianas de ROS e IL-6 em pacientes com DM1 comparados com indivíduos saudáveis (ROS ~ 4.836 vs. 2.036 RLU/min, respectivamente, P < 0,05: IL-6 ~ 14,2 vs. 9,7 pg/mL, respectivamente, P = 0,002). Diferenças não significativas (P > 0,05) foram observadas na resposta oxidante e IL-6 quando os diabéticos foram agrupados de acordo com o tempo após o diagnóstico (0-10, 10-20 e > 20 anos). A resposta antioxidante do plasma foi semelhante em pacientes com DM1 e em indivíduos saudáveis. CONCLUSÕES: Nossos resultados demonstram que as respostas oxidante e inflamatória estão aumentadas desde o início do DM1, mas mantêm-se inalteradas durante a progressão da doença, sugerindo que as mudanças funcionais envolvidas nas complicações diabéticas podem começar nos primeiros anos após o diagnóstico.

Uso materno antenatal de corticosteroide e marcadores de estresse oxidativo e de inflamação no sangue de cordão umbilical de recém-nascidos pré-termo de muito baixo peso / Antenatal maternal corticosteroid administration and markers of oxidative stress and inflammation in umbilical cord blood from very low birth weight preterm newborn infants

OBJETIVO: Avaliar a associação entre o uso materno antenatal de corticosteroide e os níveis sanguíneos de intermediários reativos de oxigênio (ROI), glutationa reduzida (GR) e interleucina-6 (IL-6) em recém-nascidos pré-termo de muito baixo peso ao nascer. MÉTODOS: Estudo de coorte. A dosagem foi feita em sangue de cordão umbilical. A dosagem de ROI por granulócitos foi realizada por citometria de fluxo nos estados basal e estimulado; a GR, por espectrofotometria; e a IL-6, por enzyme-linked immunosorbent assay. Foram considerados dois grupos em relação ao uso de corticosteroide (betametasona) antenatal: uso ou não da medicação; e, se presente, se foi de modo completo ou parcial. Variáveis maternas e neonatais foram consideradas para efeito de comparação dos grupos. As variáveis categóricas foram comparadas usando os testes do qui-quadrado ou de Fischer, e as comparações dos valores dos marcadores sanguíneos foram feitas usando-se o teste de Mann-Whitney. RESULTADOS: Os grupos de corticoterapia foram comparáveis em relação às variáveis maternas e neonatais, exceto a ocorrência de parto vaginal, o qual foi associado significativamente à ausência de uso de corticosteroide antenatal. Os valores de ROI, GR e IL-6 não se mostraram diferentes quando se avaliou a presença ou ausência da administração de esteroide; porém, quando o ciclo se fez de modo completo, encontraram-se menores medianas de ROI e IL-6. CONCLUSÃO: A administração de ciclo completo de betametasona à mãe exerceu um efeito supressor sobre a produção basal de ROI e de IL-6 em recém-nascidos pré-termo de muito baixo peso.

OBJECTIVE: To investigate the association between antenatal maternal corticosteroid administration and blood levels of reactive oxygen intermediates (ROI), reduced glutathione (GR) and interleukin-6 (IL-6) in preterm, very low birth weight infants. METHODS: This was a cohort study in which cord blood samples were used for the following tests: baseline and stimulated granulocyte ROI were measured by flow cytometry; GR was assayed by spectrophotometry; and IL-6 by enzyme-linked immunosorbent assay. Two different comparative analyses of antenatal corticosteroid (betamethasone) were conducted: the first compared administration against no administration and the second compared mothers who received the complete cycle with those given only a partial antenatal corticosteroid cycle. Maternal and neonatal variables were analyzed in order to compare groups. Categorical variables were compared using the chi-square or Fischer tests, and blood marker test results were compared using the Mann-Whitney test. RESULTS: The different corticoid therapy groups were similar in terms of all of the maternal and neonatal variables with the exception of vaginal delivery, which was significantly associated with not receiving antenatal corticosteroid. The results for ROI, GR and IL-6 did not differ when the comparison was based on simple presence or absence of administration of the steroid. However, when the complete cycle was compared against incomplete administration, median ROI and IL-6 were lower among those given the complete cycle. CONCLUSION: Administration of the complete cycle of betamethasone to the mother had a suppressive effect on baseline ROI and IL-6 production in very low birth weight preterm newborn infants.

Chromosomal abnormalities & oxidative stress in women with premature ovarian failure (POF).

Background & objectives: Premature ovarian failure (POF) is defined as the cessation of ovarian function under the age of 40 yr and is characterized by amenorrhoea, hypoestrogenism and elevated serum gonadotrophin levels. The cause of POF remains undetermined in majority of the cases. This study was aimed to investigate the type and frequency of cytogenetic abnormalities in patients with idiopathic POF and also to study the role of oxidative stress in such cases. Methods: Seventy five women with idiopathic POF were included in this study. Chromosome analysis was done in peripheral blood lymphocytes by conventional GTG banding to identify numerical or structural abnormalities. Cytogenetically normal cases were investigated for reactive oxygen species (ROS) levels in their blood by luminol-chemiluminescence assay. Results: Eighteen chromosomal anomalies were identified in POF patients (24%). Majority of the cases were found to have X-chromosome abnormalities (28%). Overall median ROS range was found to be significantly higher (P<0.01) in POF patients [50480 (120,132966) RLU/min] compared to controls [340 (120,5094) RLU/min]. Among these, 50 per cent of the POF patients had higher ROS levels, 20 per cent had medium elevation and 30 per cent were found to have normal values comparable to controls. Interpretation & conclusions: X-chromosome anomalies were found to be the major contributor of POF. Oxidative stress may be the underlying aetiology in idiopathic premature ovarian failure. Thus the results of this study highlight the role of cytogenetic abnormalities and supraphysiological levels of ROS in causation of idiopathic POF. But the role of oxidative stress needs to be confirmed by other studies on patients from different geographical areas and from different ethnicities.

Comparison of oxidative stress & leukocyte activation in patients with severe sepsis & burn injury.

Background & objectives: We evaluated pro- and anti-oxidant disturbances in sepsis and non-sepsis burn patients with systemic inflammatory response syndrome (SIRS). Adhesion molecules and inflammation markers on leukocytes were also analyzed. We hypothesized that oxidative stress and leukocyte activation markers can lead to the severity of sepsis. Methods: In 28 severe sepsis and 27 acute burn injury patients blood samples were collected at admission and 4 days consecutively. Oxidative stress markers: production of reactive oxygen species (ROS), myeloperoxidase, malondialdehyde and endogenous antioxidants: plasma protein sulphydryl groups, reduced glutathione, superoxide dismutase and catalase were measured. Flow cytometry was used to determine CD11a, CD14, CD18, CD49d and CD97 adhesion molecules on leukocytes. Procalcitonin, C-reactive protein, fibrinogen, platelet count and lactate were also analyzed. Results: Pro-oxidant parameters were significantly elevated in sepsis patients at admission, ROS intensity increased in burn patients until the 5th day. Endogenous antioxidant levels except catalase showed increased levels after burn trauma compared to sepsis. Elevated granulocyte activation and suppressed lymphocyte function were found at admission and early activation of granulocytes caused by increasing activation/migration markers in sepsis. Leukocyte adhesion molecule expression confirmed the suppressed lymphocyte and monocyte function in sepsis. Interpretation & conclusions: Severe sepsis is accompanied by oxidative stress and pathological leukocyte endothelial cell interactions. The laboratory parameters used for the evaluation of sepsis and several markers of pro- and antioxidant status were different between sepsis and non-sepsis burn patients. The tendency of changes in these parameters may refer to major oxidative stress in sepsis and developing SIRS in burns.

Beneficial effect of Berberis buxifolia Lam, Ziziphus mistol Griseb and Prosopis alba extracts on oxidative stress induced by chloramphenicol / Efecto benéfico de extractos de Berberis buxifolia Lam, Zizyphus mistol Griseb y Prosopis alba sobre el estrés oxidativo inducido por cloramfenicol

The chemiluminescence of luminol, a measure of oxidative stress, increased immediately as a consequence of reactive oxygen species (ROS) stimulated by this antibiotic. The effect of Ch was dose dependent with maximum stimulus at 8 mg/ml (Vmax); above this concentration the cells began to reduce the production of ROS. The oxidative injury of Ch was counteracted by water extracts of Berberis buxifolia lam, Zizyphus mistol Griseb and Prosopis alba, indigenous fruits from Argentina. The relatively light units (RLU) emitted decreased immediately as a consequence of a protective effect exerted by the extracts of these fruit extracts on blood cells. The three indigenous fruit extracts reduced to a different extent the oxidative injury caused by Ch. B.buxifolia lam exhibited the highest antioxidant capacity followed by Z.mistol Griseb. Water extracts of both fruit extracts were the most effective against the oxidative stress, while P.alba presented better antioxidant capacity in the ethanolic fraction obtained. Hexane extracts showed low protective action on blood cells, with little reduction of area under curve (AUC) of RLU plotted versus time. Leukocytes remained viable in blood samples incubated for 3h with Ch and water extracts of B. buxifolia lam or Z. mistol Griseb (97.1% and 92.5% viability by Trypan blue exclusion, respectively); whereas with Ch only the cells were stressed and viability decreased to 30%. The three fruit extracts protected the viability of leukocytes in parallel with the decrease of ROS. Erythrocytes were not lysed in the presence of Ch.

Se estudió el efecto antioxidante de tres extractos de frutas autóctonas, Berberis buxifolia lam (michay), Zizyphus mistol Griseb (mistol) and Prosopis alba (algarrobo). Las células sanguíneas humanas sufrieron estrés oxidativo por acción de cloramfenicol (Ch), con un aumento inmediato de especies reactivas del oxígeno (ERO), que fue determinado por quimioluminiscencia con luminol. La respuesta fue dependiente de la dosis, con un máximo a 8 mg/ml. Los extractos de frutas autóctonas de la Argentina fueron capaces de contrarrestar el estrés generado por el antibiótico. El michay y el mistol resultaron más efectivos en la fase acuosa, y el algarrobo fue más antioxidante en extractos etílicos, mientras que las fracciones obtenidas con hexano no fueron activas. La viabilidad de los leucocitos se mantuvo elevada con Ch en presencia de extractos, entre 92.5 y 97.1%, cayendo hasta un 30% con Ch solo. Tanto los eritrocitos como los leucocitos fueron protegidos del efecto estresante por la capacidad antioxidantes de los extractos de las tres frutas investigadas, lo que podría ser importante a considerar en la dieta de niños, y pacientes en general, sometidos a Ch u otras terapias causantes de estrés oxidativo.

Effect of Glutathione Administration on Serum Levels of Reactive Oxygen Metabolites in Patients with Paraquat Intoxication: A Pilot Study

BACKGROUND/AIMS: Based on preliminary in vitro data from a previous study, we proposed that 50 mg/kg glutathione (GSH) would be adequate for suppressing reactive oxygen species in patients with acute paraquat (PQ) intoxication. METHODS: Serum levels of reactive oxygen metabolites (ROM) were measured before and after the administration of 50 mg/kg GSH to each of five patients with acute PQ intoxication. RESULTS: In one patient, extremely high pretreatment ROM levels began to decrease prior to GSH administration. However, in the remaining four cases, ROM levels did not change significantly prior to GSH administration. ROM levels decreased significantly after GSH administration in all cases. In two cases, ROM levels decreased below that observed in the general population; one of these patients died after a cardiac arrest at 3 hours after PQ ingestion, while the other represented the sole survivor of PQ intoxication observed in this study. In the survivor, ROM levels decreased during the first 8 hours of GSH treatment, and finally dropped below the mean ROM level observed in the general population. CONCLUSIONS: Treatment with 50 mg/kg GSH significantly suppressed serum ROM levels in PQ-intoxicated patients. However, this dose was not sufficient to suppress ROM levels when the PQ concentration was extremely high.

Amilóide sérica A: efeitos biológicos sobre células mononucleares / Serum amyloid A: biological effects on mononuclear cells

Nos últimos anos, nosso grupo de pesquisa vem descrevendo vários efeitos da SAA em células do sistema imune no que diz respeito à expressão e liberação de citocinas pró-inflamatórias. Neste estudo centramos nossa atenção na verificação dos efeitos da SAA sobre células mononucleares. Para isto, usamos três modelos experimentais. Em murinos, descrevemos a habilidade da SAA induzir a produção de NO por macrófagos peritoneais e, com uso de animais, Knockout para TLR4, sugerimos que SAA seja um ligante endógeno do TLR4. Em células mononucleares de sangue periférico humano, a SAA induz a expressão e liberação de CCL20, uma quimiocina importante na transição da resposta imune inata para adaptativa, bem como a expressão dos fatores M-CSF e VEGF. Em células THP-1, mostramos a cinética de fosforilação de proteínas tirosina quinases promovida pela SAA e comparamos com LPS, um estímulo pró-inflamatório clássico. Ainda em células THP-1 mostramos que a SAA induz a fosforilação de duas proteínas importantes no processo inflamatório por induzirem a ativação de NFқB; a p38 e a ERK1/2. Com este estudo contribuímos com o conhecimento a respeito do papel regulatório da SAA em células mononucleares. A ação da SAA sobre estas células torna-se importante, pois estas são cruciais na resposta imune inata e também atuam como células acessórias na resposta imune adaptativa. Desta forma, evidencia-se que, no processo de fase aguda, a expressão e a síntese de SAA resultam na modulação de etapas que controlam este processo e sua progressão...

Cáncer experimental e inflamación sistémica en un modelo murino / Systemic inflammation and experimental cancer in a murine model

La asociación entre cáncer e inflamación en un órgano o tejido se encuentra sólidamente establecida. En efecto, se sabe que en sitios de inflamación crónica, existe una mayor probabilidad de que se origine un tumor y que procesos inflamatorios locales pueden acelerar el crecimiento de tumores preexistentes en animales y seres humanos. Por otro lado, la relación entre cáncer e inflamación sistémica ha sido menos estudiada. En este trabajo, demostramos que el crecimiento de un fibrosarcoma de ratón (MC-C) fue acompañado por inflamación sistémica, evidenciada por neutrofilia y por un aumento de la concentración sérica de las citoquinas pro-inflamatorias interleuquina-1 beta (IL-1 beta), interleuquina-6 (IL-6) y factor de necrosis tumoral-alfa (TNF-alfa) y de las proteínas de fase aguda C reactiva (CRP) y A amieloide (SAA). Hubo un pico de estas moléculas poco después de la inoculación del tumor, que cayó a valores normales después de la primera semana, para luego comenzar a incrementarse progresivamente en función del tamaño tumoral. Una variación similar fue vista en el porcentaje de neutrófilos polimorfonucleares (PMN) circulantes. En ratones portadores de tumores grandes la mayoría de los PMN exhibían activación evidenciada por aumento en la generación de especies reactivas del oxígeno y alta expresión de los marcadores Gr1+/Mac1+. La inoculación de tioglicolato, que produce una inflamación sistémica transitoria, aceleró el crecimiento de MC-C, mientras que el tratamiento anti-inflamatorio con indometacina revirtió ese efecto. Esto sugiere que MC-C podría utilizar el fenómeno de inflamación sistémica que genera por sí mismo, como parte de su estrategia de crecimiento.

The link between cancer and inflammation in an organ or tissue has firmly been established on the basis that cancer tends to occur at sites of chronic inflammation and that local inflammatory processes can accelerate the growth of preexisting tumors in both animals and human beings. In contrast, the relationship between cancer and systemic inflammation has been less studied. In this work, we demonstrated that the growth of the murine fibrosarcoma MC-C, was accompanied by manifestations of systemic inflammation, as demonstrated by an increase in both the number of circulating polymorphonuclear neutrophils (PMN) and the serum concentration of the proinflammatory cytokines interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) and the acute phase proteins C reactive (CRP) and serum A amyloid (SAA). Two temporally separate peaks of systemic inflammation were detected during tumor development. The first was displayed during the first week after tumor inoculation. The second peak began around day 14 and its intensity was proportional to tumor size. In mice bearing a large MC-C tumor, a high number of circulating PMN and myeloid precursors were evident. Most of these cells exhibited activation evidenced by an increased reactive oxygen species generation and high expression of the Gr1+/Mac1+ markers. Inoculation of thioglycolate -which generates a transient systemic inflammation- accelerated the growth of MC-C tumor and reciprocally, inhibition of such systemic inflammation by using indomethacin, prevented that enhancing effect. This suggests that the systemic inflammation that the tumor generates on its own, could be part of its growth strategy.

Effect on free radical generation with different anaesthesia.

Reactive oxygen species are a part of the normal physiology of the biological system but their subsequent defence undergoes alteration during diseased conditions. Administration of anaesthesia for surgery may also alter the formation of reactive oxygen species. The present work deals with the comparative status of oxidative stress (lipid peroxidation) and anti-oxidant defence markers (superoxide dismutase and catalase) in blood in 3 groups of 15 patients each receiving halothane, relaxant vecuronium and spinal form of anaesthesia with lignocaine 5% heavy. The results obtained depict that the formation of malonyl dialdehyde as well as decrease in superoxide dismutase and catalase activities was highest in spinal anaesthesia followed by halothane and then relaxant group. Therefore, it seems important to consider the pre-operative anti-oxidant status while administering anaesthesia to such patients in order to provide biologically safe anaesthesia.