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      Alveolar fractal box dimension inversely correlates with mean linear intercept in mice with elastase-induced emphysema

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          A widely applicable model of emphysema that allows efficient and sensitive quantification of injury is needed to compare potential therapies.


          To establish such a model, we studied the relationship between elastase dose and the severity of emphysema in female C57BL/6J mice. We compared alveolar fractal box dimension (D B), a new measure which is an assessment of the complexity of the tissue, with mean linear intercept (L m), which is commonly used to estimate airspace size, for sensitivity and efficiency of measurement.


          Emphysema was induced in female C57BL/6J mice by administering increasing intratracheal doses of porcine pancreatic elastase (PPE). Changes in morphology and static lung compliance (C L) were examined 21 days later. Correlation of D B with L m was determined in histological sections of lungs exposed to PPE. The inverse relationship between D B and L m was supported by examining similar morphological sections from another experiment where the development of emphysema was studied 1 to 3 weeks after instillation of human neutrophil elastase (HNE).


          L m increased with PPE dose in a sigmoidal curve. C L increased after 80 or 120 U/kg body weight ( P < 0.05), but not after 40 U/kg, compared with the control. D B progressively declined from 1.66 ± 0.002 (standard error of the mean) in controls, to 1.47 ± 0.006 after 120 U PPE/kg ( P < 0.0001). After PPE or HNE instillation, D B was inversely related to L m ( R = −0.95, P < 0.0001 and R = −0.84, P = 0.01, respectively), with a more negative slope of the relationship using HNE ( P < 0.0001).


          Intratracheal instillation of increasing doses of PPE yields a scale of progression from mild to severe emphysema. D B correlates inversely with L m after instillation of either PPE or HNE and yields a rapid, sensitive measure of emphysema after elastase instillation.

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          Most cited references 36

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          The development of emphysema in cigarette smoke-exposed mice is strain dependent.

          Only 20% of smokers develop chronic obstructive pulmonary disease. An important determinant of susceptibility is genomic variation. We undertook this study to define strains of mice with different susceptibilities for the development of smoking-induced emphysema because they could help identify genetic factors of susceptibility. NZWLac/J, C57BL6/J, A/J, SJ/L, and AKR/J strains were exposed to cigarette smoke for 6 months. Elastance (Htis), the extent of emphysema (mean linear intercept [Lm]), and the inflammatory cell and cytokine response were measured. NZWLac/J had no change in Lm or Htis (resistant). C57BL6/J, A/J, and SJ/L increased Lm, but not Htis (mildly susceptible). AKR/J increased Lm and Htis (super-susceptible). Only AKR/J had significant inflammation comprising macrophages, neutrophils, and T cells. The AKR/J showed an upregulation of Th1 cytokines whereas in the C57BL/6/J and NZWlac/J, cytokines did not change or were downregulated. We conclude that Lm, elastance, and inflammation are features that are needed to phenotype emphysema in mice. The inflammatory cell and cytokine profile may be an important determinant of the phenotype in response to cigarette smoke exposure. The identification of resistant and susceptible strains for the development of emphysema could be useful for genomic studies of emphysema susceptibility in mice and eventually in humans.
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            Fractal analysis of the vascular tree in the human retina.

             I. Masters (2003)
            The retinal circulation of the normal human retinal vasculature is statistically self-similar and fractal. Studies from several groups present strong evidence that the fractal dimension of the blood vessels in the normal human retina is approximately 1.7. This is the same fractal dimension that is found for a diffusion-limited growth process, and it may have implications for the embryological development of the retinal vascular system. The methods of determining the fractal dimension for branching trees are reviewed together with proposed models for the optimal formation (Murray Principle) of the branching vascular tree in the human retina and the branching pattern of the human bronchial tree. The limitations of fractal analysis of branching biological structures are evaluated. Understanding the design principles of branching vascular systems and the human bronchial tree may find applications in tissue and organ engineering, i.e., bioartificial organs for both liver and kidney.
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              Quantitative methods in the study of pulmonary pathology.

               M Dunnill (1962)

                Author and article information

                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                27 March 2012
                : 7
                : 235-243
                [1 ]Division of Pulmonary, Critical Care, and Environmental Medicine, Department of Internal Medicine, University of Missouri
                [2 ]Research Services, Harry S Truman Memorial VA Hospital, Columbia, MO, USA
                Author notes
                Correspondence: Rajiv Dhand, Division of Pulmonary, Critical Care and Environmental Medicine, One Hospital, Drive, Columbia MO, USA 65212, Tel +1 57 3884 7806, Fax +1 57 3884 4892, Email dhandr@
                © 2012 Andersen et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                Original Research


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