CXCL11 attenuates bleomycin-induced pulmonary fibrosis via inhibition of vascular remodeling

Aberrant vascular remodeling is a central hallmark for the development and progression of idiopathic pulmonary fibrosis. The mechanisms underlying the pathophysiologic alterations, however, are poorly understood. A recent phase II trial of interferon gamma-1b has demonstrated a trend toward a decrease in profibrotic and proangiogenic biologic markers, and upregulation of lung CXCL11 mRNA and bronchoalveolar lavage fluid and plasma protein levels of CXCL11. We hypothesized that net aberrant vascular remodeling seen during the pathogenesis of fibroplasia and deposition of extracellular matrix during bleomycin-induced pulmonary fibrosis can be attenuated by treatment with the angiostatic ELR(-) CXC chemokine, CXCL11. In a preclinical model, systemic administration of CXCL11 reduced pulmonary collagen deposition, procollagen gene expression, and histopathologic fibroplasia and extracellular matrix deposition in the lung of bleomycin-treated mice. CXCL11 treatment significantly reduced bleomycin-induced pulmonary fibrosis without altering specific lung leukocyte populations. CXCR3 is not expressed on fibroblasts and CXCL11 had no direct functional effect on pulmonary fibroblasts. The angiogenic activity in the lung was significantly decreased, however, and CXCL11 treatment reduced the total number of endothelial cells in the lung following bleomycin exposure. The results suggest that CXCL11 inhibits pulmonary fibrosis by altering aberrant vascular remodeling.     

Pharmacology of angioplasty and intravascular thrombolysis

Interventional angiographic techniques are of increasing importance in the management of arteriosclerosis and its complications. Two areas of particular interest are the treatment of focal arterial stenoses by percutaneous transluminal angioplasty and the treatment of arterial thromboemboli with selective infusion of thrombolytic agents. The administration of multiple drugs, in various combinations, is a critical factor in the success of these interventions. To effectively use this new pharmacoangiography, it is important to understand both the pathophysiology of the atherosclerotic or thrombotic process being treated and the actions of the drugs used. Preserving the effect of angioplasty relies on preventing thrombus formation and preventing recurrence of the atherosclerotic obstruction. Heparin during the procedure is clearly useful for the former, and aspirin in small doses and other antiplatelet medications are indicated for the latter. The precise utility of long-term anticoagulation, of low molecular weight dextran, and of various antiplatelet regimens remains to be proven. The theoretical importance of these medications in improving long-term patency rests on the effects they have on platelet and vessel wall prostaglandins, on intimal smooth muscle cell proliferation, and on the thrombogenicity of injured arterial intima. Fibrinolytic therapy, with streptokinase and urokinase, has been used for many years. Selective intraarterial use, however, is a new and promising application. Intracoronary streptokinase infusion during acute myocardial ischemia appears to prevent or limit infarction in certain patients. Peripheral use for acute arterial occlusion, either in native vessels or in grafts, is an area of great promise. Key considerations are thrombus age, size, and location, and the status of the arterial flow proximal and distal to the obstruction.     

Effects of supplemental zinc on melanoma metastasis in mice

The influence of a single intraperitoneal injection of zinc (0.5, 1.5 and 4.5 mg/kg) on the metastasis and subsequent growth of radiolabelled melanoma cells was examined in mice receiving tumor cells s.c. or i.v. 24 h following zinc treatment. Parenteral zinc resulted in increased tumor cell survival in the liver, spleen and lungs of zinc-treated mice 1 day post-injection, while 21-day cell survival was enhanced in the spleens of s.c. injected, zinc-treated mice. Regardless of zinc exposure, relative numbers of s.c. injected tumor cells decreased with time in the lungs and spleen, while increasing in the liver and kidneys. A single dose of zinc can modify the organ distribution and viability of metastatic tumor cells in mice.     

Short incubation non-A, non-B hepatitis transmitted by factor VIII concentrates in patients with congenital coagulation disorders.

Ten cases are reported of short incubation (one to four weeks) non-A, non-B hepatitis occurring after infusion of various preparations of factor VIII concentrates into patients with coagulation disorders. Five patients were symptomatic and, in all, serum transaminase levels were increased for at least six months. These cases of chronic hepatitis exhibited none of the features of autoimmune chronic hepatitis: autoantibodies were negative and serum immunoglobulins were normal. Hepatic histology confirmed acute hepatitis in two cases biopsied early in the illness, and chronic active hepatitis (three) of chronic persistent hepatitis (two) in five cases studied later. Lobular inflammation was a prominent feature in all cases. Other features not commonly associated with type A or B hepatitis included fatty change and damaged bile ducts.     

Quantification of fluorescein distribution to strangulated rat ileum

Following various periods of strangulation, the fates of intestinal segments were predicted by standard clinical criteria and visual (Wood's lamp) and fluorometric (perfusion fluorometer) assessment of fluorescein distribution. With fluorometry, a means of quantifying fluorescence transmitted via a fiberoptic light guide, the delivery and removal of fluorescein were monitored and analyzed. If either was restricted significantly, tissue death was predicted. Analysis of computerized graphic patterns or simple interpretation of fluorometric readings at two time points predicted tissue fate with 98% accuracy and a 93% negative predictive value. Wood's lamp evaluation had only a 53% accuracy and a 33% negative predictive value, while standard clinical criteria had an 81% accuracy and a 53% negative predictive value. Fluorescein leakage in segments which suffered significant endothelial damage provided staining patterns that incorrectly suggested viability. By monitoring elimination as well as uptake of dye, fluorometry provided much greater discrimination than did Wood's lamp inspection in this setting. In addition, fluorometry was readily repeatable within minutes, as fluorescence remaining from a previous injection could be subtracted from new, postinjection values.     

Computed tomography in the evaluation of musculoskeletal neoplasms

In a study of 62 musculoskeletal neoplasms, computed tomography contributed little to establishing tissue diagnosis. Its primary value lay in the assessment of intraosseous and/or extraosseous extent of disease. CT also established the presence or absence of disease in a small number of cases with clinically questionable findings. In most cases, conventional radiographic methods were superior in diagnosing musculoskeletal neoplasms.