Eduardo Tavares Lima Trajano

Redox Imbalance and Pulmonary Function in Bleomycin-Induced Fibrosis in C57BL/6, DBA/2, and BALB/c Mice

The development of bleomycin-induced pulmonary fibrosis (BLEO-PF) has been associated with differences in genetic background and oxidative stress status. The authors’ aim was to investigate the crosstalk between the redox profile, lung histology, and respiratory function in BLEO-PF in C57BL/6, DBA/2, and BALB/c mice. BLEO-PF was induced with a single intratracheal dose of bleomycin (0.1 U/mouse). Twenty-one days after bleomycin administration, the mortality rate was over 50% in C57BL/6 and 20% in DBA/2 mice, and BLEO-PF was not observed in BALB/c. There was an increase in lung static elastance (p < .001), viscoelastic/inhomogeneous pressure (p < .05), total pressure drop after flow interruption (p < .01), and ΔE (p < .05) in C57BL/6 mice. The septa volume increased in C57BL/6 (p < .05) and DBA/2 (p < .001). The levels of IFN-γ were reduced in C57BL/6 mice (p < .01). OH-proline levels were increased in C57BL/6 and DBA/2 mice (p < .05). SOD activity and expression were reduced in C57BL/6 and DBA/2 mice (p < .001 and p < .001, respectively), whereas catalase was reduced in all strains 21 days following bleomycin administration compared with the saline groups (C57BL/6: p < .05; DBA/2: p < .01; BALB/c: p < .01). GPx activity and GPx1/2 expression decreased in C57BL/6 (p < .001). The authors conclude that BLEO-PF resistance may also be related to the activity and expression of SOD in BALB/c mice.

Endotoxin-induced acute lung injury is dependent upon oxidative response

The aim of the present study was to investigate the involvement of oxidative stress in acute lung injury (ALI) induced by lipopolysaccharide (LPS) and its effects upon cell structure, function and inflammation. In total, 108 male C57BL/6 mice were divided into seven groups: CTR Group (50 µL of saline) administered intratracheally (i.t.), LPS 6 h (10 µg of LPS − i.t.), LPS 12 h (10 µg of LPS − i.t.), LPS 24 h (10 µg of LPS − i.t.), LPS 48 h (10 µg of LPS − i.t.), LPS 24 h (10 µg − i.t.) + NAC 40 mg/kg (gavage) and 24 h LPS (10 µg − i.t.) + NAC 100 mg/kg (gavage). The antioxidant treatment protected the lungs from stress in the first 12 h, but significant oxidative stress induction was observed at the 24-hour time point, and, after 48 h, there was no protection exerted by the antioxidant treatment. NAC (N-acetylcysteine) reversed the elastance parameters, and ΔP1 and ΔP2 compared with 24 h LPS alone. NAC reduced the number of inflammatory cells in histology analysis when compared with the 24 h LPS alone-treated group. NAC also inhibited the transcription of NFκB, IL-6, TNF-α and COX2 usually induced by LPS. Our results suggest that oxidative stress plays an important role in structural, functional and inflammatory responses in the ALI model.

Heat delays skin wound healing in mice.

In vivo studies have shown that the combination of infrared radiation (IR) and visible light (VIS) is responsible for the activation of metaloproteinases, causing matrix degradation and damage to healthy skin. However, the role of heat originating from the VIS spectrum on wound healing remains poorly understood. Our objective was to investigate the macroscopic, microscopic and biochemical effects of heat induced by visible light on cutaneous wound healing in mice. Male mice were anesthetized, subjected to a cutaneous excisional wound and divided into two groups (n = 10/group) exposed to 23℃ or 43℃ in a thermal chamber for 30 min every other day, for 13 days. On day 14, the animals were sacrificed, and their lesions were processed for histochemistry, immunohistochemistry and protein expression analysis. The wound area was 42% greater 11 days (p < 0.01) and 29% greater 14 days (p < 0.001) after wounding in the 43℃ group than in the 23℃ group. The 43℃ group presented a lower (17%) percentage of reepithelialized wounds (p < 0.001) 14 days after wounding. The length of the epidermal gap was greater in the 43℃ group (p < 0.01). The volume density of myofibroblasts and the number of F4/80-positive macrophages was greater in the 43℃ group (p < 0.05). The 43℃ group showed increased protein expression of type III collagen (p < 0.001), decreased protein expression of type I collagen (p < 0.05), increased MMP-1 expression (p < 0.05), and decreased MMP-2 activity (p < 0.001). The protein expression of fibrillin-1 (p < 0.001), MMP-12 (p < 0.05), TGF-β 1/2/3 (p < 0.01) and ERK activation (p < 0.05) was increased in the 43℃ group. Our results suggest that heat delays the stages of wound healing in mice.

Elastase modifies bleomycin-induced pulmonary fibrosis in mice.

Pulmonary fibrosis (PF) is characterized by excessive accumulation of collagen in the lungs. Emphysema is characterized by loss of the extracellular matrix (ECM) and alveolar enlargement. We studied the co-participation of elastase-induced mild emphysema in bleomycin-induced PF in mice by analyzing oxidative stress, inflammation and lung histology. C57BL/6 mice were divided into four groups: control; bleomycin (0.1U/mouse); elastase (using porcine pancreatic elastase (PPE)+bleomycin (3U/mouse 14 days before 0.1U/mouse of bleomycin; PPE+B); elastase (3U/mouse). Mice were humanely sacrificed 7, 14 and 21 days after treatment with bleomycin or vehicle. PF was observed 14 days and 21 days after bleomycin treatment but was observed after 14 days only in the PPE+B group. In the PPE+B group at 21 days, we observed many alveoli and alveolar septa with few PF areas. We also observed marked and progressive increases of collagens 7, 14 and 21 days after bleomycin treatment whereas, in the PPE+B group, collagen deposition was observed only at 14 days. There was a reduction in activities of the antioxidant enzymes superoxide dismutase (p<0.05), catalase (p<0.01) and glutathione peroxidase (p<0.01) parallel with an increase in nitrite (p<0.01) 21 days after bleomycin treatment compared with the control group. These endpoints were also reduced (p<0.05, p<0.05 and p<0.01, respectively) and increased (p<0.01) in the PPE+B group at 21 days compared with the control group. Interleukin (IL)-1β expression was upregulated (p<0.01) whereas IL-6 was downregulated (p<0.05) in the PPE+B group at 21 days compared with the control group. PF and emphysema did not coexist in our model of lung disease and despite increased levels of oxidative stress and inflammatory markers after combined stimulus (elastase and bleomycin) overall histology was improved to that of the nearest control group.

DOENÇA DE CUSHING POR MACROADENOMA: RELATO DE CASO

Apresentar um caso de Sindrome de Cushing (SC) induzido por macroadenoma. Metodo: Paciente de 48 anos com obesidade centripeta, fraqueza muscular proximal, diabetes melito (DM) e disturbios menstruais, cuja investigacao diagnostica demonstrou tratar-se de macroadenoma hipofisario. Resultados: Paciente foi submetida a varios exames laboratoriais no qual foi verificado elevados niveis de ACTH. Alem disso, foi realizado ressonância magnetica da sela turcica e do abdomen no qual foi verificado a origem hipofisaria. Apos exames foi realizada resseccao transesfenoidal de hipofise eletivamente, entretanto evoluiu com suspeita de recidiva. Conclusao: Com base no quadro clinico atual apesar da estrategia terapeutica ter sido acertada exames laboratoriais sugerem uma possivel reincidiva do caso, entretanto, se faz necessario o acompanhamento da evolucao do quadro clinico para verificacao do desfecho final.

Allgrove syndrome and motor neuron disease

Allgrove or triple A syndrome (AS or AAA) is a rare autosomal recessive syndrome with variable phenotype due to mutations in AAAS gene which encodes a protein called ALADIN. Generally, it’s characterized by of adrenal insufficiency in consequence of adrenocorticotropic hormone (ACTH) resistance, besides of achalasia, and alacrimia. Neurologic features are varied and have been the subject of several case reports and reviews. A few cases of Allgrove syndrome with motor neuron disease have been already described. A 25-year-old white man, at the age of four, presented slowly progressive distal amyotrophy and weakness, autonomic dysfunction, dysphagia and lack of tears. He suffered later of orthostatic hypotension and erectile dysfunction. He presented distal amytrophy in four limbs, tongue myofasiculations, alacrimia, hoarseness and dysphagia due to achalasia. The ENMG showed generalized denervation with normal conduction velocities. Genetic testing revealed 2 known pathogenic variants in the AAAS gene (c.938T>C and c.1144_1147delTCTG). Our case presented a distal spinal amyotrophy with slow evolution and symptoms and signs of AS with a mutation in AAAS gen. Some cases of motor neuron disease, as ours, may be due to AAS. Early diagnosis is extremely important for symptomatic treatment.

Relationship between Attention Deficit Hyperactivity Disorder and Ocular Convergence Insufficiency: Future Perspectives

Recent studies suggest that the ocular convergence insufficiency (OCI) and the attention deficit hyperactivity disorder (ADHD) present a superposition of signs and symptoms which can be correlated. In this context, OCI may guide the clinical diagnostic of ADHD in children, teenagers and adults. Different authors propose that the search for signs and symptoms of OCI must be performed during the diagnostic process of ADHD, since it is an easy and lowcost examination procedure. The aim of this short communication is to discuss this subject and to present future perspectives on this theme.

Genomic stability and telomere regulation in skeletal muscle tissue

Muscle injuries are common, especially in sports and cumulative trauma disorder, and their repair is influenced by free radical formation, which causes damages in lipids, proteins and DNA. Oxidative DNA damages are repaired by base excision repair and nucleotide excision repair, ensuring telomeric and genomic stability. There are few studies on this topic in skeletal muscle cells. This review focuses on base excision repair and nucleotide excision repair, telomere regulation and how telomeric stabilization influences healthy muscle, injured muscle, exercise, and its relationship with aging. In skeletal muscle, genomic stabilization and telomere regulation seem to play an important role in tissue health, influencing muscle injury repair. Thus, therapies targeting mechanisms of DNA repair and telomeric regulation could be new approaches for improving repair and prevention of skeletal muscle injuries in young and old people.

Challenges of Airway Management in EmergencySituations: A Literature Review

The management of the airways in emergency situations is considered one of the main life-saving acts [1]. According to Advanced Trauma Life Support recommendations for the management of patients with life-threatening injuries, airway protection is the first intervention [2]. Endotracheal intubation is the technique of choice because it is a fast, more frequently successful procedure and allows the use of a larger tube [1,2]. They are indications for endotracheal intubation and emergency: maintenance of airway permeability, respiratory failure unrelated to upper airway obstruction, decreased risk of aspiration of gastric contents [2]. Evidence corroborated the findings that the efficacy of bag-valve-mask use in emergencies, most emergency intubations occur in situations of cardiorespiratory arrest, the difference in the development of pneumonia due to invasive airway management in a pre-operative environment -hospital and hospital are not significant and the combination of ketamine and propofol (known as cetofol) is an alternative for etomidate in sedation for maintaining hemodynamic stability [2-11]. The objective of this study is to perform a review on the management of the airways in emergency situations.

Estudo retrospectivo de pacientes diagnosticados com câncer de mamainternados em hospital universitário

O câncer de mama e a segunda neoplasia com maior incidencia na populacao feminina, sendo o primeiro, o câncer de pele nao melanoma. A concentracao de quase 70% da populacao em grandes centros favorece a exposicao aos fatores de risco ambientais, aos quais e atribuida relacao direta ou indireta com 80% dos casos de câncer. Algumas substâncias quimicas, o tabagismo, a poluicao ambiental e a disparidade socioeconomica podem gerar influencia na distribuicao e na incidencia do câncer nas diferentes regioes brasileiras. O estudo teve como objetivo realizar uma analise retrospectiva de pacientes, diagnosticadas com câncer de mama internadas em Hospital Universitario Sul Fluminense, Vassouras (RJ), entre o periodo de janeiro de 2010 a abril de 2014. A idade variou entre 20 a 90 anos, com idade media de 57,4 anos, em que houve predominio da faixa etaria de 50 a 59 anos. Em relacao a cor da pele, notou-se maior incidencia em mulheres brancas (51%). De acordo com a classificacao histologica, o carcinoma predominante foi o do tipo ductal invasivo grau 2 de Nottingham. Com base nos nossos resultados, concluimos que o tipo de câncer com maior incidencia ocorreu em grande parte em mulheres brancas e que o tratamento preconizado para a maioria dos casos foi a remocao cirurgica, sendo associada a outra estrategia terapeutica, principalmente a quimioterapia. Breast cancer is the second cancer with the highest incidence on the female population, and the firstis the non-melanoma skin cancer. The concentration of nearly 70% of the population in big citiesfavors exposure to environmental risk factors, which is attributed a direct or indirect relation to 80%of cancer cases. Some chemicals, smoking, environmental pollution and socioeconomic disparity cangenerate influence on the distribution and incidence of cancer in different Brazilian regions. Thestudy aimed at carring out a retrospective analysis of patients diagnosed with breast cancer admittedto a University Hospital Sul Fluminense, Vassouras (RJ), Brazil, in the period from January 2010 toApril 2014. The age ranged from 20 to 90 years, the mean age was 57.4 years, in which there was apredominance of the age group 50-59 years. With regard to skin color, it was seen a higher incidencein white women (51%). According to histological classification, the predominant cell carcinoma wasinvasive ductal type 2 grade of Nottingham. Based on our results, we conclude that the type of cancerwith the highest incidence occurred largely in white women and the treatment recommended formost cases was the surgical removal that was associated with another therapeutic strategy, especiallychemotherapy.