Variation of the Intercellular Space in the Esophageal Epithelium in Response to Hydrochloridric Acid Infusion in Patients with Erosive Esophagitis

The purpose of this study was to compare esophageal infusion with 0.1 N hydrochloridric acid (HCl) to esophageal infusion with saline in patients presenting with typical gastroesophageal reflux symptoms and erosive esophagitis. METHODS: Upper gastrointestinal endoscopy was performed on 44 prospective subjects, 29 of whom were included in the study. Eighteen patients presented with normal esophagi (Control Group "C"), nine of whom were infused with HCl and nine with saline. Eleven patients presented with erosive esophagitis (Lesion Group "L"), five of whom were infused with HCl and six with saline. Biopsies of the esophageal mucosa were collected before and after infusions. RESULTS: No statistically significant difference was found between the two types of infusions in terms of the dilation of the intercellular space of the esophageal epithelium, regardless of the status of the patient. CONCLUSIONS: Response to HCl infusion cannot be used as a marker for gastroesophageal reflux disease

Baroreflex Impairment Precedes Cardiometabolic Dysfunction in an Experimental Model of Metabolic Syndrome: Role of Inflammation and Oxidative Stress

This study analyzes whether autonomic dysfunction precedes cardiometabolic alterations in spontaneously hypertensive rats (SHR) with fructose overload. Animals were randomly distributed into three groups: control, hypertensive and hypertensive with fructose overload. Fructose overload (100 g/L) was initiated at 30 days old, and the animals (n = 6/group/time) were evaluated after 7, 15, 30 and 60 days of fructose consumption. Fructose consumption reduced baroreflex sensitivity by day 7, and still induced a progressive reduction in baroreflex sensitivity over the time. Fructose consumption also increased TNFα and IL-6 levels in the adipose tissue and IL-1β levels in the spleen at days 15 and 30. Fructose consumption also reduced plasmatic nitrites (day 15 and 30) and superoxide dismutase activity (day 15 and 60), but increased hydrogen peroxide (day 30 and 60), lipid peroxidation and protein oxidation (day 60). Fructose consumption increased arterial pressure at day 30 (8%) and 60 (11%). Fructose consumption also induced a late insulin resistance at day 60, but did not affect glucose levels. In conclusion, the results show that baroreflex sensitivity impairment precedes inflammatory and oxidative stress disorders, probably by inducing hemodynamic and metabolic dysfunctions observed in metabolic syndrome.Fil: Bernardes, Nathalia. Universidade de Sao Paulo; BrasilFil: Da Silva Dias, Danielle. Universidade Nove de Julho; BrasilFil: Fernandes Stoyell Conti, Filipe. Universidade de Sao Paulo; BrasilFil: De Oliveira Brito Monzani, Janaina. Universidade Nove de Julho; BrasilFil: Malfitano, Christiane. Universidade Nove de Julho; BrasilFil: Garcia Caldini, Elia. Universidade de Sao Paulo; BrasilFil: Ulloa, Luis. Universidade Nove de Julho; BrasilFil: Llesuy, Susana Francisca. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica. Cátedra de Química General e Inorgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Irigoyen, Maria Cláudia. Universidade de Sao Paulo; BrasilFil: De Angelis, Kátia. Universidade Nove de Julho; Brasi

Iodine increases and predicts incidence of thyroiditis in NOD mice : histopathological and ultrastructural study

Prolonged intake of large amounts of iodine has been reported to increase the incidence of hypothyroidism in humans, as well as in animals which are prone to spontaneously developing autoimmune thyroiditis. We sought to investigate the histopathological consequences of large amounts of dietary iodine on the thyroid gland and observe the occurrence of lymphocytic infiltration associated with the time of exposure to iodine. An experimental model using non-obese diabetic (NOD) mice was analyzed. A potassium iodide intake of 0.2 mg/animal/day was administered via drinking water, in experimental groups of 60 and 90 days (EG60 and EG90). Distended rough endoplasmic reticulum, degenerated mitochondria, debris and amorphous spaces or ‘ill-defined’ spaces were observed with electron microscopy (EM). Lymphocyte infiltration was observed in the two groups and the time of exposure to iodine did not increase the appearance of lymphocyte infiltration but significantly associated with the development of necrosis. The results of the present study demonstrated that the NOD mouse is a feasible experimental model for thyroiditis induced by iodine administration and may represent an opportunity to analyze the steps and factors associated with genetic autoimmune thyroiditis. High doses of ingested iodine were observed to precdict and increase the incidence of the thyroiditis process

Tumour cells incorporate exosomes derived from dendritic cells through a mechanism involving the tetraspanin CD9

Exosomes (Exos) are secreted nanovesicles that\ud contain membrane proteins and genetic material, which\ud can be transferred between cells and contribute to their\ud communication in the body. We show that Exos, obtained\ud from mature human dendritic cells (DCs), are incorporated\ud by tumour cells, which after Exos treatment, acquire the\ud expression of HLA‐class I, HLA‐class II, CD86, CD11c,\ud CD54 and CD18. This incorporation reaches its peak eight\ud hours after treatment, can be observed in different cell\ud tumour lines (SK‐BR‐3, U87 and K562) and could be a\ud means to transform non‐immunogenic into immunogenic\ud tumour cells. Interestingly, tetraspanins, which are\ud expressed by the tumour cells, have their surface level\ud decreased after Exo treatment. Furthermore, the intensity\ud of Exo incorporation by the different tumour cell lines was\ud proportional to their CD9 expression levels and pretreatment\ud of Exos with anti‐CD9 decreased their\ud incorporation (by SK‐BR‐3 cells). This modification of\ud tumour cells by DC‐derived Exos may allow their use in\ud new immunotherapeutic approaches to cancer.\ud Furthermore, by showing the involvement of CD9 in this\ud incorporation, we provide a possible selection criterion for\ud tumours to be addressed by this strategyFundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP, #04/09956-0)Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP, #07/58597-1)Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP, #09/54599-5)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, #303731/2007-9

Aerobic Exercise Attenuated Bleomycin-Induced Lung Fibrosis in Th2-Dominant Mice

Introduction The aim of this study was to investigate the effect of aerobic exercise (AE) in reducing bleomycin- induced fibrosis in mice of a Th2-dominant immune background (BALB/c). Methods BALB/c mice were distributed into: sedentary, control (CON), Exercise-only (EX), sedentary, bleomycin-treated (BLEO) and bleomycin-treated+exercised (BLEO+EX);(n = 8/group). Following treadmill adaptation, 15 days following a single, oro-tracheal administration of bleomycin (1.5U/kg), AE was performed 5 days/week, 60min/day for 4 weeks at moderate intensity (60% of maximum velocity reached during a physical test) and assessed for pulmonary inflammation and remodeling, and cytokine levels in bronchoalveolar lavage (BAL). Results At 45 days post injury, compared to BLEO, BLEO+EX demonstrated reduced collagen deposition in the airways (p<0.001) and also in the lung parenchyma (p<0.001). In BAL, a decreased number of total leukocytes (p<0.01), eosinophils (p<0.001), lymphocytes (p<0.01), macrophages (p<0.01), and neutrophils (p<0.01), as well as reduced pro-inflammatory cytokines (CXCL-1;p<0.01), (IL-1 beta;p<0.001), (IL-5;p<0.01), (IL-6;p<0.001), (IL-13;p<0.01) and pro-fibrotic growth factor IGF-1 (p<0.001) were observed. Anti-inflammatory cytokine IL-10 was increased (p<0.001). Conclusion AE attenuated bleomycin-induced collagen deposition, inflammation and cytokines accumulation in the lungs of mice with a predominately Th2-background suggesting that therapeutic AE (15-44 days post injury) attenuates the pro-inflammatory, Th2 immune response and fibrosis in the bleomycin model

Diagnosis of primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a genetic disorder of ciliary structure or function. It results in mucus accumulation and bacterial colonization of the respiratory tract which leads to chronic upper and lower airway infections, organ laterality defects, and fertility problems. We review the respiratory signs and symptoms of PCD, as well as the screening tests for and diagnostic investigation of the disease, together with details related to ciliary function, ciliary ultrastructure, and genetic studies. In addition, we describe the difficulties in diagnosing PCD by means of transmission electron microscopy, as well as describing patient follow-up procedures

Citoesqueleto e mecanotransdução na fisiopatologia da lesão pulmonar induzida por ventilador Cytoskeleton and mechanotransduction in the pathophysiology of ventilator-induced lung injury

A ventilação mecânica é uma terapia importante, mas pode resultar em complicações. Uma das mais relevantes é a lesão pulmonar induzida por ventilador. Devido à hiperdistensão alveolar, o pulmão inicia um processo inflamatório, com infiltrado neutrofílico, formação de membrana hialina, fibrogênese e prejuízo de troca gasosa. Nesse processo, a mecanotransdução da hiperdistensão celular é mediada através do citoesqueleto da célula e de suas interações com a matriz extracelular e com as células vizinhas, de modo que o estímulo mecânico da ventilação se traduz em sinalização bioquímica intracelular, desencadeando ativação endotelial, permeabilidade vascular pulmonar, quimiotaxia leucocitária, produção de citocinas e, possivelmente, lesão de órgãos à distância. Estudos clínicos demonstram essa relação entre distensão pulmonar e mortalidade em pacientes com lesão pulmonar induzida por ventilador. Entretanto, apesar de o citoesqueleto ter um papel fundamental na patogênese da lesão pulmonar induzida por ventilador, a literatura carece de estudos utilizando modelos in vivo sobre as alterações do citoesqueleto e de suas proteínas associadas durante esse processo patológico.<br>Although mechanical ventilation is an important therapy, it can result in complications. One major complication is ventilator-induced lung injury, which is caused by alveolar hyperdistension, leading to an inflammatory process, with neutrophilic infiltration, hyaline membrane formation, fibrogenesis and impaired gas exchange. In this process, cellular mechanotransduction of the overstretching stimulus is mediated by means of the cytoskeleton and its cell-cell and cell-extracellular matrix interactions, in such a way that the mechanical stimulus of ventilation is translated into an intracellular biochemical signal, inducing endothelial activation, pulmonary vascular permeability, leukocyte chemotaxis, cytokine production and, possibly, distal organ failure. Clinical studies have shown the relationship between pulmonary distension and mortality in patients with ventilator-induced lung injury. However, although the cytoskeleton plays a fundamental role in the pathogenesis of ventilator-induced lung injury, there have been few in vivo studies of alterations in the cytoskeleton and in cytoskeleton-associated proteins during this pathological process