Vascular Hyperpermeability Case Study

Lung inflammation will be scored by a treatment-blind observer. The degree of peribronchial and perivascular inflammation will be evaluated on a subjective scale of 0-3, as described previously [37]. Briefly, A value of 0: no inflammation is detectable; a value of 1: occasional cuffing with inflammatory cells; a value of 2: most bronchi or vessels are surrounded by a thin layer (one to five cells thick) of inflammatory cells; a value of 3: majority of bronchi or vessels are surrounded by a thick layer (more than five cells thick) of inflammatory cells. Total lung inflammation will be defined as the average of the peribronchial and perivascular inflammation scores. Five lung sections per mouse will be scored and inflammation scores will be expressed as a mean

Subsequently, it increases pulmonary pressure and pushes fluids in the capillaries out into the alveolar spaces resulting in congestive heart failure. This series of events can demonstrate fluid overload in the lungs that can cause dyspnea, which may affect an individual overall functional capacity and thus result in cardiopulmonary deconditioning. Pan et al. (2014) describes this medicine as a direct adrenergic agonist that acts exactly on β1 agonist in the heart and partly β2 receptor (lungs); it produces an active contraction of the ventricles to increase the heart’s cardiac output and degrades pulmonary resistance minimally through vasodilation hence, decreasing pulmonary congestion.

I note lung function tests performed in September revealed normal spirometry with no change post-bronchodilator, whilst gas transfer is mildly reduced.

In the meanwhile, in the cytoplasm, the hemagglutinin and neuraminidase have undergone glycosylation, polymerization, and acylation. The hemagglutinin, neuraminidase, and the matrix protein two (M2) all travel together to the plasma membrane. There the proteins meet with the other matrix protein (M1), and begin the

This causes further damage to the lung. This hyperinflation of the lung is known as emphysema. In emphysema, the alveoli are permanently enlarged leading to a dramatic decline in the alveolar surface area available for gas exchange (Workman, 2013). The permanent enlargement of the alveoli is caused by the overabundance of proteases. When proteases are present in higher-than-normal levels, alveoli is damaged as the proteases break down the elastin located within the lung. When elastin is broken down, lung elasticity is decreased and air is permanently trapped within the air spaces (Workman, 2013). These overall changes from both bronchitis and emphysema lead to hypoxemia, decreased oxygenation, and respiratory

Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating and life-threatening, interstitial lung disease of unknown etiology that has no cure (1). The median survival of patients with IPF is only 2 to 3 years. Respiratory failure resulting from this disease progression is the most frequent cause of death. Continuous damage to the alveolar epithelium and concomitant alveolar type II (ATII) cell apoptosis are thought to lead to fibroblast recruitment, accumulation and proliferation and contribute to the perpetuation of the fibrotic scarring and IPF development. ATII cells synthesize, store, and secrete

Though many advances were made & multiple research done, in 2012 the medical community once again got together. An expert panel agreed that ARDS is a type of acute diffuse, inflammatory lung injury, leading to increased pulmonary vascular permeability, increased lung weight, and loss of aerated lung tissue. “The clinical hallmarks are hypoxemia and bilateral radiographic opacities, associated with increased venous admixture, increased physiological dead space, and decreased lung compliance. The morphological hallmark of the acute phase is diffuse alveolar damage (ie, edema, inflammation, hyaline membrane, or hemorrhage).”3 It was at this conference that the Berlin definition was put into existence. Though it is to note that most research to date has been done using the AECC definition, the Berlin definition removed what was known as acute lung injury. Under the new Berlin definition patients with a PaO2/FiO2 ratio of 200-300 while on a PEEP of +5 would now be classified as mild ARDS, while patients with a PaO2/FiO2 ratio of 100-200 would be classified as moderate & anything under 100 would be classified as severe. With pulmonary capillary wedged pressures under 18mm HG. The Berlin definition defined acute stating that the maximum period between risk factor exposure and ARDS

0.043), was dropped gradually from 12 h (FC=1.01) and markedly suppressed 24 h after the high-dose I+ treatments (FC= -1.48, p-value=0.006

Atherosclerosis is a lipid storage disease where too much of lipid is deposited in endothelial of arteries causing narrowing to prevent blood to flow. It is triggered by daily diet of consuming highly saturated fat, hypertension and smoking. In healthy endothelial cells, leukocytes do not stick on to the endothelial cells. During early phases of inflammation in endothelial cells, the leukocytes attach to the arteries cell wall with the help of vascular cell adhesion-1 (VCAM-1) and penentrate into the endothelial layer. VCAM-1 binds monocytes and T lymphocytes, the types of leukocytes found in early atherosclerotic plaques. ( Libby P., 2006:456S) Atherosclerosis lesion is a foam cells whereby macrophages engulf lipid particles. The lesion secretes cytokines and growth factors to promote proliferation of smooth muscle. The increased of inflammatory markers like interleukin 6 (IL-6) and interleukin 1 (IL-1) accumulated in the endothelial cells accerlate the progess of

As a consequence of host defense activity at the site as in case of PMN activity.

Sepsis is a serious life-threatening condition that arises when the body’s overwhelming immune response to a widespread infection begins to injure its own tissues and organs (Hinkle & Cheever, 2014). At the cellular level, sepsis is characterized by changes in the function of endothelial tissue, in the coagulation process, and blood flow. These changes are initiated by the cellular release of pro-inflammatory substances known as cytokines in response to the presence of infectious microorganisms. The cytokines then interact with the endothelial cells, which results in damage and even possible death of those endothelial cells. As a result, coagulation factors become activated, which in combination with endothelial damage, may hinder blood flow

Vasoconstriction of the blood vessel is the initial stage in which it limits the blood flow at the site of injury. With the help of thrombin platelets become activated and aggregated via activation of protease-activated receptors (PARs) on the surface of the platelet cell membrane. During coagulation, prothrombin is converted to thrombin in the presence of Ca2+, though these functions involve numerous cleavage reactions. Thrombin has a vital role in clot promotion and inhibition,

Efficient inhibition of the fibrin deposition and thrombus formation by plasma protease FXIIa-neutralizing antibody, 3F7, by binding specifically to the enzymatic pocket of FXIIa in an extracorporeal membrane oxygenation (ECMO) system similar to heparin but without treatment associated increase in hemorrhage signifies thromboprotective properties of 3F7. Further, inhibition of the thrombus formation without impairing the hemostasis indicates FXII as a potential target for prevention of atherothrombosis. The use of ECMO simulating the clinical settings signifies the meaningful importance of this study to use in clinics. However, the prevention of the contact-induced FXIIa formation, thrombus formation in mice and rabbits and coagulation in-vitro with 3F7 has also been documented [59,60,61] (Figure 2). FXII activation is also mediated by inorganic polymer polyphosphate (polyP), which is stored in platelets and secreted on platelet activation [36]. Reduced fibrin accumulation and attenuated thrombus formation without increased risk

Injury to the endothelial cells will then decrease production of NO and this will enable the accumulation of lipids. As the build-up progress and permeability decreases, macrophages infiltration and release of pro-inflammatory cytokines occur. The damage caused by oxidation causes a compensatory response which increases the endothelial adhesiveness to leukocytes and platelets via cell adhesion molecule upregulation. Circulating monocytes and leukocytes initially bind cell adhesion molecules on the endothelial surface, but chemokines are required for recruitment into the subendothelial space. Once monocytes enter the subendothelial space, they may mature into macrophages leading to formation of foam cells and then eventually to the appearance of “fatty streaks” in the arteries. As lesion severity progresses into a fibroatheroma, macrophages, T-cells and mast cells penetrate the cap edges and stimulate the production and movement of vascular smooth muscle cells. Vascular smooth muscle cells contribute to plaque growth through producing pro-inflammatory cytokines that attract and activate leukocytes, generate VSMC proliferation, express adhesion molecules that

Dr. Kosmider has publications with Dr. Steven Kelsen, who is a co-investigator on this grant. His clinical and research interests are focused on signaling pathways and the pathophysiology of oxidant stress-induced epithelial injury. He has training in respiratory medicine and physiology and will provide knowledge of the lung diseases. He has also collaborated with Dr. Muniswamy Madesh, a co-investigator in this project, who is an expert in studies of mitochondrial dysfunction and mechanisms of mitochondrial induced apoptosis.