Galectin-3 (Gal-3) has a role in multiple inflammatory pathways. Various, opposite roles of Gal-3 in liver diseases have been described but there are no data about the role of Gal-3 in development of hepatitis induced with cytomegalovirus infection. In this study we aimed to clarify the role of Gal-3 in murine cytomegalovirus (MCMV)-induced hepatitis by using Gal-3–deficient (Gal-3 KO) mice. Here we provide the evidence that Gal-3 has the protective role in MCMV-induced hepatitis. Enhanced hepatitis manifested by more inflammatory and necrotic foci and serum level of ALT, enhanced apoptosis and necroptosis of hepatocytes and enhanced viral replication were detected in MCMV-infected Gal-3 deficient mice. NK cells does not contribute to more severe liver damage in MCMV-infected Gal-3 KO mice. Enhanced expression of TNF-α in the hepatocytes of Gal-3 KO mice after MCMV infection, abrogated hepatocyte death, and attenuated inflammation in the livers of Gal-3 KO mice after TNF-α blockade suggest that TNF-α plays the role in enhanced disease in Gal-3 deficient animals. Treatment with recombinant Gal-3 reduces inflammation and especially necrosis of hepatocytes in the livers of MCMV-infected Gal-3 KO mice. Our data highlight the protective role of Gal-3 in MCMV-induced hepatitis by attenuation of TNF-α-mediated death of hepatocytes.
Low Reynolds number airflow in the pulmonary acinus and aerosol particle kinetics therein are significantly conditioned by the nature of the tidal motion of alveolar duct geometry. At least two components of the ductal structure are known to exhibit stress-strain hysteresis: smooth muscle within the alveolar entrance rings, and surfactant at the air-tissue interface. We hypothesize that the geometric hysteresis of alveolar duct is largely determined by the interaction of the amount of smooth muscle & connective tissue in ductal rings, septal tissue properties, and surface tension-surface area characteristics of surfactant. To test this hypothesis, we have extended the well-known structural model of the alveolar duct by Wilson and Bachofen (J. Appl. Physiol. 52(4): 1064–1070, 1982) by adding realistic elastic and hysteretic properties of 1) the alveolar entrance ring, 2) septal tissue, and 3) surfactant. With realistic values for tissue and surface properties, we conclude that: 1) there is a significant, and underappreciated, amount of geometric hysteresis in alveolar ductal architecture; and 2) the contribution of smooth muscle and surfactant to geometric hysteresis are of opposite senses, tending toward cancellation. Quantitatively, the geometric hysteresis found experimentally by Miki et al. (J. Appl. Physiol. 75(4): 1630–1636, 1993) is consistent with little or no smooth muscle tone in anesthetized rabbits in control conditions, and with substantial smooth muscle activation following methacholine challenge. The observed local hysteretic boundary motion of the acinar duct would result in irreversible acinar flow fields, which might be important mechanistic contributors to aerosol mixing and deposition deep in the lung.
Acute pancreatitis is characterized by autodigestion of pancreatic cells followed by acute inflammation leading to pathology and death. In experimental acute pancreatitis, pancreatic acinar cells and infiltrating macrophages express Galectin-3 but its role in pathology of this disease is unknown. Therefore, we studied its role using Galectin-3 deficient mice. Deletion of Galectin-3 prolonged the survival of mice, led to attenuation of histopathology, and decreased infiltration of mononuclear cells and neutrophils that express TLR-4, in particular, pro-inflammatory N1 neutrophils. Galectin-3 and TLR-4 are also colocalized on infiltrating cells. Lack of Galectin-3 reduced expression of pro-inflammatory TNF-α and IL-1β in F4/80 + CD11c-and CD11c + F4/80 − cells. Thus, deletion of Galectin-3 ameliorates acute pancreatitis by attenuating early influx of neutrophils and inflammatory mononuclear cells of innate immunity. These findings provide the basis to consider Galectin-3 as a therapeutic target in acute pancreatitis.Keywords: acute pancreatitis r Galectin-3 r N1 neutrophils r TLR4
Clinical characteristics significantly influence mortality in STEMI; a significantly higher mortality is among women, patients in their 80's and 90's, anterior MI localization and prior coronary disease. RT significantly lowers mortality in STEMI compared to the use of classical therapeutic approach and therefore STEMI patients with a higher mortality determined by their prehospital charactheristics, i.e. higher risk, are those who have higher benefit of RT, which should be taken into consideration when making decision about the therapy of choice.
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