Histamine is a biogenic amine that is widely distributed and has multiple functions, but the role it plays in acute myocardial infarction (AMI) remains unclear. In this study, we investigated the origin and contribution of endogenous histamine to AMI. Histidine decarboxylase (HDC) is the unique enzyme responsible for histamine generation. Using HDC-EGFP bacterial artificial chromosome (BAC) transgenic mice in which EGFP expression is controlled by the HDC promoter, we identified HDC expression primarily in CD11b+Gr-1+ immature myeloid cells (IMCs) that markedly increase in the early stages of AMI. Deficiency of histamine in HDC knockout mice (HDC−/−) reduced cardiac function and exacerbated the injury of infarcted heart. Furthermore, administering either an H1 receptor antagonist (pyrilamine) or an H2 receptor antagonist (cimetidine) demonstrated a protective effect of histamine against myocardial injury. The results of in vivo and in vitro assays showed that histamine deficiency promotes the apoptosis of cardiomyocytes and inhibits macrophage infiltration. In conclusion, CD11b+Gr-1+ IMCs are the predominant HDC-expressing sites in AMI, and histamine plays a protective role in the process of AMI through inhibition of cardiomyocyte apoptosis and facilitation of macrophage infiltration.

Four vegetable oils with typical fatty acid compositions were chosen to determine their indicators of lipid oxidation under the conditions of accelerated oxidation. Good linear correlations were observed between the total nonpolar carbonyl amount and the total oxidation value (TOTOX, R(2) = 0.89-0.97) or peroxide value (POV, R(2) = 0.92-0.97) during 35 days of accelerated oxidation. Additionally, nonanal in camellia oil (oleic acid mainly) increased significantly, and correlated linearly with TOTOX (21.6 TOTOX - 595, R(2) = 0.92); propanal increased significantly in perilla oil (linolenic acid mainly) and correlated linearly with TOTOX (8.10 TOTOX + 75.0, R(2) = 0.90). Hexanal (9.56 TOTOX + 913, R(2) = 0.90, and 7.10 TOTOX + 342, R(2) = 0.78, respectively) and nonenal (10.5 TOTOX + 691, R(2) = 0.95, and 6.65 TOTOX + 276, R(2) = 0.84, respectively) in sunflower oil (linoleic acid mainly) and palm oil (palmitic and oleic acids mainly) also had good linear correlations with TOTOX. Considering the change patterns of these four aldehydes, it was found that the oxidation stability was in the order sunflower oil < camellia oil < perilla oil < palm oil, which was same as POV, TOTOX, and total nonpolar carbonyls. It was concluded that the four aldehydes nonanal, propanal, hexanal, and nonenal could be used as oxidation indicators for the four types of oils.

Primary PAS is often mistaken for chronic pulmonary thromboembolism. Surgical intervention is the mainstay of treatment for PAS, but the prognosis after surgery remains poor. Compared to isolated tumour resection, pulmonary endarterectomy seemed to yield a better survival rate.

No abstract

Histamine has pleiotropic pathophysiological effects, but its role in myocardial infarction (MI)-induced cardiac remodeling remains unclear. Histidine decarboxylase (HDC) is the main enzyme involved in histamine production. Here, we clarified the roles of HDC-expressing cells and histamine in heart failure post-MI using HDC-EGFP transgenic mice and HDC-knockout (HDC−/−) mice. HDC+CD11b+ myeloid cell numbers markedly increased in the injured hearts, and histamine levels were up-regulated in the circulation post-MI. HDC−/− mice exhibited more adverse cardiac remodeling, poorer left ventricular function and higher mortality by increasing cardiac fibrogenesis post-MI. In vitro assays further confirmed that histamine inhibited heart fibroblast proliferation. Furthermore, histamine enhanced the signal transducer and activator of transcription (STAT)-6 phosphorylation level in murine heart fibroblasts, and the inhibitive effects of histamine on fibroblast proliferation could be blocked by JAK3/STAT6 signaling selective antagonist. STAT6-knockout (STAT6−/−) mice had a phenotype similar to that of HDC−/− mice post-MI; however, in contrast to HDC−/− mice, the beneficial effects of exogenous histamine injections were abrogated in STAT6−/− mice. These data suggest that histamine exerts protective effects by modulating cardiac fibrosis and remodeling post-MI, in part through the STAT6-dependent signaling pathway.

CCAAT enhancer binding protein-α (C/EBP-α) is a transcript factor that regulates adipocyte differentiation and induces apoptosis in hepatic stellate cells (HSCs) in vivo and in vitro. However, the effect of C/EBP-α on hepatocytes in vivo remains unknown. This study investigated whether C/EBP-α exerts different apoptotic effects on hepatocytes and HSCs in vitro and in vivo. An adenovirus vector-expressing C/EBP-α gene was constructed, and a rat hepatic stellate cell lines (HSC-T6) and hepatocytes were transfected. A CCl(4)-induced liver fibrosis model in mice was also utilized. C/EBP-α induced apoptosis in hepatocytes and HSCs, but a significant difference between these cell types was observed in vitro. The mitochondrial pathway was involved in the apoptotic process and was predominant in HSC-T6 apoptosis. In the CCl(4)-induced mice liver fibrosis model, the administration of Ad-C/EBP-α decreased extracellular matrix deposition, including collagen and hydroxyproline content, and γ-GT levels, a marker of liver damage, were reduced significantly. Immunohistochemistry and TUNEL assay results showed an increase of apoptosis in HSCs, but hepatocytes were less affected. C/EBP-α induced differential apoptotic effects in hepatocytes and HSCs in vitro and in vivo. This differential effect could be a potential target for the treatment of hepatic fibrosis with little hepatic toxicity.

No abstract

No abstract