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.
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.
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.
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
Acute pancreatitis (AP) is a common, potentially lethal, acute inflammatory process with a highly variable clinical course. The aim of this study was to analyse early changes in the serum concentrations of pro- and anti-inflammatory cytokines in the peripheral blood of patients with the interstitial form of acute pancreatitis (IAP) and necrotic acute pancreatitis (NAP), especially in those patients who had lethal outcomes.The prospective study enrolled 52 patients who were divided into IAP (65.38% of patients) and NAP (34.62% of patients) groups. The serum levels of interleukins (IL) 6, 8 and 10, together with tumour necrosis factor (TNF)-alpha were measured on the 1st and 3rd day of hospitalisation. Significantly higher values of IL-6, IL-8 and IL-10 were found on day 1 and 3 in NAP than in IAP. IL-6 was significantly higher on both days of measurement, whereas IL-10 on the first day and IL-8 on the third day were significantly higher in the group of patients who did not survive in comparison with patients who had the interstitial form of AP.In conclusion, the data from this study showed that immune suppression and excessive immune stimulation in the first three days after admission could indicate the development of NAP and a potentially lethal outcome.
An immune-mediated, severe, acquired prothrombotic disorder, heparin-induced thrombocytopenia type II (HIT II) occurs in 0.5-5% of patients exposed to unfractionated heparin longer than 5-7 days. Arterial and venous thromboses are induced by HIT II in about 35-50% of patients. Typical death rate for HIT is about 29%, while 21% of HIT patients result in amputation of a limb. The trend towards the occurrence of HIT due to the administration of low molecular weight heparins (LMWH) taking ever conspicuous place in the standard venous thromboembolism (VTE) prophylaxis has been more frequently observed recently. It is considered that LMWH may cause HIT II in about 0.25-1%. The need for further modification of HIPA assays with LMWH has been imposed in the HIT laboratory diagnostics, heretofore overburdened with complexity. There are several constantly opposing problems arising in HIT laboratory diagnostics, one of which is that in a certain number of patients immunologic assays detect nonpathogenic antibodies (mainly IgM or IgA heparin-PF4 antibodies) while, on the other hand, the occurrence of HIT pathogenetically mediated by minor antigens (neutrophil-activating peptide 2 or interleukin 8) may be neglected in certain cases. The following factors play an important role in the interpretation of each laboratory HIT assays performed: 1. correlation with HIT clinical probability test, the best known of which is 4T'score, 2. the interpretation of the laboratory findings dependent on the time of the thrombocytopenia onset, as well as 3. the sensitivity and specificity of each test respectively. The HIT diagnostics in the presence of other comorbid states which may also induce thrombocytopenia, more precisely known as pseudo HIT (cancer, sepsis, disseminated intravascular coagulation, pulmonary embolism, antiphospholipid syndrome, etc), represents a specific clinical problem.
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