The role of mast cells in cutaneous wound healing in streptozotocin-induced diabetic mice.

Mast cells (MCs) reside in cutaneous tissue, and an increment of MCs is suggested to induce vascular regression in the process of wound healing. To clarify participation of MCs in diabetic cutaneous wound healing, we created an excisional wound on diabetic mice 4 weeks after streptozotocin injections and subsequently investigated the healing processes for 49 days, comparing them with control mice. The rate of wound closure was not markedly different between the diabetic and control mice.

Proteomic comparison between abdominal and thoracic aortic aneurysms.

The pathogenesis of abdominal aortic aneurysms (AAAs) and that of thoracic aortic aneurysms (TAAs) is distinct. In this study, to reveal the differences in their biochemical properties, we performed quantitative proteomic analysis of AAAs and TAAs compared with adjacent normal aorta (NA) tissues. The proteomic analysis revealed 176 non-redundant differentially expressed proteins in the AAAs and 189 proteins in the TAAs which were common in at least 5 samples within 7 samples of each.

Proteomic analysis of calcified abdominal and thoracic aortic aneurysms.

Aortic aneurysm is a complex multifactorial disease with genetic and environmental risk factors. It is often accompanied by aortic calcification. Here, to uncover proteins that are significantly changed in calcified abdominal aortic aneurysms (CAAs) and calcified thoracic aortic aneurysms (CTAs) compared with those in adjacent normal aorta tissues, comprehensive analysis of differentially expressed proteins in their tissues was performed by a quantitative proteomic approach with iTRAQ labeling in combination with nanoLC-MALDI-TOF/TOF-MS/MS followed by ProteinPilot analysis.

Pranlukast, a cysteinyl leukotriene type 1 receptor antagonist, attenuates the progression but not the onset of silica-induced pulmonary fibrosis in mice.

Background: Although cysteinyl leukotrienes (CysLTs) have been implicated in the etiology of acute inflammatory diseases, recent studies have suggested that they also directly stimulate fibroblasts. However, their precise role in the pathogenesis of pulmonary fibrosis is unclear.

Methods: In this study, we evaluated the effect of both short- and long-term treatment with pranlukast, a CysLT type 1 (CysLT(1)) receptor antagonist, on silica-induced pulmonary fibrosis in mice, which is characterized by persistent progression of fibrosis in the chronic phase.

Effects of montelukast, a cysteinyl-leukotriene type 1 receptor antagonist, on the pathogenesis of bleomycin-induced pulmonary fibrosis in mice.

Cysteinyl-leukotrienes are potent mediators involved in various inflammatory diseases and lung disorders such as asthma. However, their precise role in the pathogenesis of pulmonary fibrosis is unknown. In the present study, we investigated the effect of montelukast, a cysteinyl-leukotriene type 1 receptor antagonist, on bleomycin-induced pulmonary fibrosis in mice.

Involvement of leukotrienes in the pathogenesis of silica-induced pulmonary fibrosis in mice.

The authors investigated the role of leukotrienes (LTs) in the pathogenesis of silica-induced pulmonary fibrosis in mice during the progression from acute to chronic phases. Intratracheal instillation of silica particles induced progressive pulmonary fibrosis. The tissue content of cysteinyl (Cys) LTs and LTB(4) was markedly increased in the acute phase after silica instillation, concurrently with the up-regulation of LTB(4) receptor, transforming growth factor (TGF)-beta1, and tumor necrosis factor (TNF)-alpha, along with down-regulation of the CysLT type 2 receptor.

Pathophysiological role of skin mast cells in wound healing after scald injury: study with mast cell-deficient W/W(V) mice.

Background: The major role of mast cells in wound healing process has not been identified. In this study, we used mast cell-deficient W/W(V) mice and their congenic control (+/+) mice to examine the role of mast cells in scald wound healing.

Methods: The size of the scald wound, thickness of the dermis, collagen deposition, vascularization, number of mast cells and chymase activity were measured before and at 3, 7, 14 and 21 days after inducing scald injury.

A disynaptic pathway from the central amygdaloid nucleus to the paraventricular hypothalamic nucleus via the parastrial nucleus in the rat.

The organization of projections from the central amygdaloid nucleus (CeA) to the paraventricuilar hypothalamic nucleus (PVH) has been studied in order to understand the anatomical substrates of amygdaloid modulation of endocrine and autonomic functions, and a hypothesis that the bed nucleus of the stria terminalis (BST) may act as a relay site between the CeA and PVH has been proposed. Using anterograde and retrograde tract-tracing methods, in the rat, we first indicated that neurons in the parastrial nucleus (PS), where projection fibers from the central amygdaloid nucleus (CeA) terminated, sent their axons to the paraventricular hypothalamic nucleus (PVH). We further demonstrated that the CeA terminals formed symmetrical synaptic contacts with somata and dendrites of the PVH-projecting PS neurons, and that the PS received CeA fibers predominantly from the lateral part and sent large numbers of projection fibers to almost all the subdivisions of the PVH.

Pathophysiological role of mast cells in collagen-induced arthritis: study with a cysteinyl leukotriene receptor antagonist, montelukast.

Our previous study showed that the number of mast cells was increased in the inflamed paws of collagen-induced arthritis in mice, and treatment with a mast cell-stabilizing compound effectively suppressed the development of collagen-induced arthritis. A recent in vitro study showed that mast cells express cysteinyl leukotriene type 1 receptor, and that a cysteinyl leukotriene type 1 receptor antagonist inhibits the production of TNF-alpha by mast cells. To further investigate the role of mast cells in vivo, we evaluated the therapeutic effects of a cysteinyl leukotriene type 1 receptor antagonist, montelukast, on the development of collagen-induced arthritis in mice.

Effect of mast cell chymase inhibitor on the development of scleroderma in tight-skin mice.

1 Although the pathogenesis of scleroderma is not fully understood, activation of connective-tissue-type mast cells (CTMCs) has been implicated in various fibrotic diseases. 2 Our previous study showed that the number of CTMCs was markedly increased during fibrous proliferation in the skin of a scleroderma model, namely tight-skin (Tsk) mice. Because mast cells express numerous bioactive factors, such as cytokines, growth factors, proteases, and others, it is crucial to identify the primary factors that may be involved in the pathogenesis of scleroderma.

Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo.

APJ is a G-protein-coupled receptor with seven transmembrane domains, and its endogenous ligand, apelin, was identified recently. They are highly expressed in the cardiovascular system, suggesting that APJ is important in the regulation of blood pressure. To investigate the physiological functions of APJ, we have generated mice lacking the gene encoding APJ.

Mast cells as a target of rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) is a chronic inflammatory disease and its exact cause and pathophysiological process remain unclear. Fibroblast-like synoviocytes, macrophages and T lymphocytes are considered to be the major contributors in the pathophysiological process of RA; however, an increasing number of papers have drawn attention to the potential role of mast cells (MCs) in the process. In an animal model of RA, we reported an increase in MC numbers in the arthritic region, which agreed with the observation in human RA.

Cardiotoxic interaction of metabolites from a prodrug segment cilexetil (cyclohexyloxy-carbonyloxy-ethyl) with digoxin in the canine failing heart.

Potential risks of cyclohexanol (CH) and cyclohexanediol (CHD) isomers, which are the metabolites derived from cilexetil ester side-chain of several prodrugs such as antibiotics (e.g. cefotiam hexetil) and an antihypertensive agent (candesartan cilexetil), were examined in beagles that were made congestive heart failure (CHF) by rapid ventricular pacing.

Comparative study on salivary distribution of fluoroquinolones in rats.

As a basic approach to identifying the distribution mechanism of quinolone antibiotics into saliva, salivary excretion of five fluoroquinolones, ciprofloxacin (CPFX), norfloxacin (NFLX), lomefloxacin (LFLX), ofloxacin (OFLX) and sparfloxacin (SPFX), was compared in rats. Blood, parotid and mandibular saliva were periodically collected from the anesthetized rats after bolus i.v.

Cutaneous malignant fibrous histiocytoma with the characteristics of different variants.

We report the case of a 50-year-old woman with cutaneous malignant fibrous histiocytoma (MFH) on the right hypogastric region. A purplish-red blood-filled tumor, approximately 40 mm in diameter, was detected on the region. A histopathologic analysis of the excised tumor showed that it extended from the upper dermis to the subcutaneous tissue over the fascia and, furthermore, that a variety of cells, from highly atypical spindle shaped to histiocytelike, were embedded in the collagenous stroma without forming a capsule.