Intraluminal thrombus is a consistent feature of human abdominal aortic aneurysm (AAA). Coagulation factor Xa (FXa) catalyses FII to thrombin (FIIa). We examined the effect of FXa/FIIa inhibition on experimental aortic aneurysm in apolipoprotein E-deficient (ApoE−/−) mice infused with angiotensin II (AngII). The concentration of FXa within the supra-renal aorta (SRA) correlated positively with SRA diameter. Parenteral administration of enoxaparin (FXa/IIa inhibitor) and fondaparinux (FXa inhibitor) over 14 days reduced to severity of aortic aneurysm and atherosclerosis in AngII-infused ApoE−/− mice. Enteral administration of the FIIa inhibitor dabigatran had no significant effect. Aortic protease-activated receptor (PAR)-2 expression increased in response to AngII infusion. Fondaparinux reduced SRA levels of FXa, FIIa, PAR-2, matrix metalloproteinase (MMP)2, Smad2/3 phosphorylation, and MOMA-2 positive cells in the mouse model. FXa stimulated Smad2/3 phosphorylation and MMP2 expression in aortic vascular smooth muscle cells (VSMC) in vitro. Expression of MMP2 in FXa-stimulated VSMC was downregulated in the presence of a PAR-2 but not a PAR-1 inhibitor. These findings suggest that FXa/FIIa inhibition limits aortic aneurysm and atherosclerosis severity due to down-regulation of vascular PAR-2-mediated Smad2/3 signalling and MMP2 expression. Inhibition of FXa/FIIa may be a potential therapy for limiting aortic aneurysm.
CHzCOCH3], has been tested for its antifertility activity in male albino rats. The oral administration of this compound at the dose level 6.5 rag/rat/day reduced the weights of testes and epididymides. Significant decrease in sperm motility as well as sperm density resulted in the reduction of male fertility by 100%. Production of primary spermatocytes (preleptotene and pachytene), secondary spermatocytes and step-19 spermatids declined by 56.10%, 44.42 %, 63.35 % and 64.57 % respectively. These results indicate that the administration of compound (1) in male rats brought about an interference with spermatogenesis which ultimately caused infertility.
Background: Idiopathic hypereosinophilic syndrome (HES) is a rare and potentially lethal disorder characterized by persistently elevated eosinophil counts without any underlying causes. Two variants, the myeloproliferative and lymphocytic hypereosinophilic syndrome, have been identified. The symptoms are variable and related to the organs involved (cardiovascular system, skin, central and peripheral nervous system, gastrointestinal tract, eyes). Skin lesions can be the dominating and/or presenting symptom in about 50% of patients.
Main observations:We describe a 54-year-old man with a 12-year history of skin lesions, clinically consistent with psoriasis and psoriatic erythroderma. The patient was treated with methotrexate with no response. He experienced intense pruritus, dry/coarse skin and palmoplantar hyperkeratosis. Histopathology showed spongiotic dermatitis with no epidermotropism. Inflammatory infiltrates in upper dermis consisted predominantly of lymphocytes and eosinophils. Peripheral and tissue eosinophilia, immunophenotyping, and results of FIP1L1-PDGFRA gene analysis were suggestive of lymphocytic HES. The patient was treated with hydroxycarbamide (1 g/day), prednisolone (40 mg/day) and antihistamines with improvement.Conclusions: HES requires early treatment to prevent severe damage of targeted organs. The pleomorphic dermatological manifestations may delay the diagnosis. This case shows the importance of wide differential diagnosis of erythroderma. In this article we discuss the diagnostic criteria, the recommended work-up and management of idiopathic hypereosinophilic syndrome variants. (J Dermatol Case Rep.
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