Minimally invasive neuroradiologic model of preclinical transient middle cerebral artery occlusion in canines

Stroke is currently the third leading cause of death in the United States, with approximately 780,000 Americans affected by a new or recurring stroke each year. Although a variety of therapeutic approaches have shown promise in small-animal models of stroke, the vast majority of clinical trials to test the efficacy of such modalities have failed. To bridge the translational gap between laboratory and clinical research, we developed a preclinical model of acute ischemic stroke in dogs. Using a minimally invasive endovascular approach, a platinum coil was intravascularly guided through the vertebrobasilar system under C-arm fluoroscopy to occlude the M1 segment of the middle cerebral artery (MCA) for 1 h. The approach included femoral artery catheterization to access the MCA and therefore eliminated the occurrence of head trauma associated with other preclinical stroke models relying on transorbital or craniectomy approaches. After 1 h of focal MCA ischemia, the coil was retrieved to cause reperfusion, which was verified by arteriograms. At 24 h, T2-weighted coronal magnetic resonance (MR) images were acquired and processed for three-dimensional reconstruction of the brain and its vasculature. Infarction, limited to the area at risk, was noted. Two independent observers calculated the mean percentage hemispherical lesion volumes as follows: observer 1, 30.9 ± 2.1%; observer 2, 31.2 ± 4.3%. Infarct-affected changes in histology were determined by hematoxylin and eosin as well as by Fluoro-Jade staining. This work reports the successful development of a powerful preclinical model of stroke that lends itself to the study of biologic mechanisms as well as to testing experimental therapeutics.     

Immune responses to Aspergillus antigen in IL‐4‐/‐ mice and the effect of eosinophil ablation

BACKGROUND: Exposure to Aspergillus fumigatus allergens results in enhanced total serum IgE and peripheral blood eosinophils in mice. The associated pulmonary inflammation and immunologic responses are comparable to those detected in human allergic bronchopulmonary aspergillosis. Allergen-induced cytokines are thought to regulate the inflammatory and immune responses in these animals. METHODS: In the present study, we exposed C57BL/6 and BALB/c mice to A. fumigatus antigen. Both wild-type and IL-4 knockout phenotypes of animals of both strains were used. Some animals were also treated with anti-IL-5 or anti-IFN-gamma. Total serum IgE, Aspergillus species IgG subclass, peripheral blood eosinophils, and lung histology were studied. RESULTS: The results demonstrate similar lung inflammation in all wild-type and IL-4-/- animals exposed to A. fumigatus antigen. Similarly, in spite of the diverse immune response produced by the anticytokine treatment, no major differences were detected among any of the animal groups studied. CONCLUSIONS: It can be concluded that A. fumigatus exposure in an immunologically unaltered host is predominantly of a Th2 type, and that depletion of the Th2 cytokine leads to a similar lung inflammation but with a characteristic Th1 response, suggesting that the pathogenesis of allergic aspergillosis is the result of multiple induction pathways.     

Smoking Is Underrecognized as a Risk Factor for Chronic Pancreatitis

Background/Aims: Smoking is an established risk factor for chronic pancreatitis (CP). We sought to identify how often and in which CP patients physicians consider smoking to be a risk factor. Methods: We analyzed data on CP patients and controls prospectively enrolled from 19 US centers in the North American Pancreatitis Study-2. We noted each subject's self-reported smoking status and quantified the amount and duration of smoking. We noted whether the enrolling physician (gastroenterologist with specific interest in pancreatology) classified alcohol as the etiology for CP and selected smoking as a risk factor. Results: Among 382/535 (71.4%) CP patients who were self-reported ever smokers, physicians cited smoking as a risk factor in only 173/382 (45.3%). Physicians cited smoking as a risk factor more often among current smokers, when classifying alcohol as CP etiology, and with higher amount and duration of smoking. We observed a wide variability in physician decision to cite smoking as a risk factor. Multivariable regression analysis however confirmed that the association of CP with smoking was independent of physician decision to cite smoking as a risk factor. Conclusions: Physicians often underrecognize smoking as a CP riskfactor. Efforts are needed to raise awareness of the association between smoking and CP.