S. Maslinski

Isolated Placental Vessel Response to Vascular Endothelial Growth Factor and Placenta Growth Factor in Normal and Growth-Restricted Pregnancy

Vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) cause vasodilation. We examined the vasomotor response of isolated placental vessels to VEGF and PlGF in normal (group I) and intrauterine growth retardation (IUGR)-complicated pregnancy (group II). Rings of vessels were prepared in vitro and mounted on the vessel myograph plunged in tissue bath. The magnitude of dilation to increased doses of VEGF and PlGF has been studied. VEGF is a more potent vasodilator than PlGF. Both, VEGF- and PlGF-induced vasorelaxation was diminished in the IUGR (group II) nearly by half, compared to control (group I). Relative placental nitric oxide deficiency, or decreased sensitivity to VEGF and PlGF may contribute to the development of high impedance fetoplacental circulation.

Distribution of tryptase-containing mast cells and metallothionein reactive astrocytes in human brains with amyloid deposits.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder of the elderly, causing severe and permanent impairment of multiple cognitive faculties. The two most striking pathological features of AD are extracellular deposits of beta-amyloid plaques in the cerebral cortex and intracellular neurofi brillary tangles of hyperphosphorylated tau proteins [1]. A variety of different mechanisms has been suggested to contribute to neuronal death in AD, including genetic and environmental factors [2, 3]. Increasing data support the hypothesis that infl ammation is involved in the pathogenesis of the disease [4]. Mast-cell tryptase is a protease with proinfl ammatory activity and an important indicator of mast cell activation and degranulation [5]. Metallothionein (MT) has several putative roles in metal detoxifi cation, in scavenging free radicals, and in acute phase responses [6]. Therefore, we have studied the distribution of these two proteins in the brains of individuals with AD and in brains of patients who died within a few minutes after cardiac arrest.

Mast cell-derived VEGF and VEGF receptor type 1, 2, and 3 expression in human term trophoblast culture—influence of hypoxia

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6. Human and clinical aspects of histamine

Rheumatoid arthritis (RA) is a chronic infl ammatory disease, characterized mainly by immunological disturbances and synovial infl ammation. The importance of various endogenous mediators was confi rmed in the development of RA, however the pathogenesis of RA remains still unclear [1, 2]. Arthritic synovium manifests many pathological changes. During synovium infl ammation critical events such as neoangiogenesis, cellular hyperplasia and a massive infl ux of infl ammatory cells occurs. Normal synovial tissue consists of a scraggly intimal lining and the synovial sublining, however RA synovial tissue manifests oedema. Finally, in RA, this results in the formation of a mass of tissue (“pannus”) which serves as the origin of joint erosion [2]. Histamine is an important chemical mediator which acts at the site of infl ammation. Mast cells present in synovium are major sources of histamine [1, 3]. There are four subtypes of histamine receptors; H1, H2, H3 and H4 [4]. The H4R is proposed to be exclusively expressed on the cells with hematopoietic lineage (eosinophils, T cells, dendritic cells, basophils and mast cells) [5, 6]. Excess of expression of H4R in organs of the immune system (e. g. spleen, thymus and leukocytes) has implicated H4R in the immune system [3, 7]. The H4R mediates eosinophil histamine-induced chemotaxis and has a role in secretion of IL-16 from CD8+ T cells. Activation of H4R can cause calcium mobilization and chemotaxis in mast cells [7, 8]. While the presence of H4R in cultured synovial cells of RA patients has been documented by RTPCR technique [3], the distribution pattern of this receptor in the synovial tissue has not yet been determined. Materials and methods

Histamine H4 receptors on mammary epithelial cells of the human breast with different types of carcinoma

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Expression of histamine H4 receptor in human osteoarthritic synovial tissue

Osteoarthritis (OA) is a progressive non-infl ammatory disorder of the joints caused by gradual loss of cartilage and resulting in the development of bony spurt and cysts with the most common location being the knee [1]. Histamine (H) affects a variety of functions in the human body including joints. Mast cells present in the synovium are the major source of histamine [2]. They often increase in number at site of active cartilage erosion. Recently histamine has been implicated in the pathophysiological processes of OA and H receptors H1 and H2 as well as histamine decarboxylase expression were demonstrated immunohistochemically in OA chondrocytes [3]. This suggests that immuno/infl ammatory reactions are involved in the pathogenesis of OA. Histamine receptors are classifi ed into four subtypes, H1, H2, H3 and H4. The histamine H4 (HH4) receptor is a member of G-protein coupled receptors (GPCRs) and preferentially expressed on the cells of hematopoietic lineage (eosinophils, T cells, dendritic cells, basophils and mast cells) [4]. We have previously shown that the novel HH4 receptor is localized in synoviocytes found in infl amed tissue of patients with rheumatoid arthritis (RA) [5]. Here we report the studies of expression of HH4 receptor in various types of synovial cells of patients with OA.

Taurine chloramine modifies adjuvant arthritis in rats.

No Abstract..

Is lymphocyte histamine involved in the pathogenesis of rheumatoid arthritis

The pathogenesis of rheumatoid arthritis (RA) is multifactorial; several cytokines and other inflammatory mediators are involved in the induction and perpetuation of the chronic inflammatory process of the joints and in the systemic manifestations of the disease [1]. Although neurotransmitters and various chemical mediators also play an important role in the pathogenesis of rheumatoid arthritis, the precise underlying mechanisms have yet to be determined. Histamine is a classical mediator of the inflammatory process and together with other mediators may influence the progress of RA [2]. Due to its proinflammatory actions, histamine increases the classical symptoms of inflammation in the periarticular area, as well acting directly on the cells of this site [3]. The interest in lymphocytes and their role in rheumatic diseases has markedly increased. This can be partially explained by the discovery that lymphocytes can themselves synthesise histamine [4]. Further studies have shown the local participation of lymphocytes to be a rich source of histamine in the area of the inflamed joint [5]. Alterations in the levels of histamine secreted by lymphocytes may markedly influence the course of RA. The aim of this study was to evaluate whether the secretion of histamine from lymphocytes is different in healthy individuals when compared to those with RA. A further aim was to establish which factors stimulate and which inhibit this process.

Antihistaminic drugs modify casein-induced inflammation in the rat

IntroductionAll known antihistaminics may affect several inflammatory events, including chemotaxis, the survival of eosinophils, and the release of chemokines and cytokines from different sources, thus highlighting the potential for modulating chronic inflammation and immune responses. The aim of the study was to examine the effect of H1–H4 antihistaminic drugs in an acute model of casein-induced inflammation in rat.Materials and methodsInflammation was induced by injection of a 12% solution of casein into the peritoneal cavity of male Wistar rats. The rats were treated intraperitoneally with pyrilamine maleate (10 mg/kg), cimetidine (25 mg/kg), thioperamide maleate (2 mg/kg) or ciproxifan hydrogen maleate (0.14 mg/kg) twice: 2 hours prior and 4 hours after casein administration. The level of histamine in blood and chemiluminescence of stimulated and unstimulated PMNs was measured.ResultsThe level of histamine in the casein-induced inflammation group was higher than in the control group. Treatment with pyrilamine and ciproxifan additionally increased the level of blood histamine during the inflammatory response. Peripheral blood neutrophils from rats with casein-induced inflammation tended to respond less to zymosan stimulation than the neutrophils in the controls. Selective H1 and H3 antagonists injected into the rats with casein-induced inflammation significantly increased the response of the neutrophils to zymosan (p < 0.01).ConclusionHistamine produced or released into the blood in the course of experimental inflammation exerts its effects on the PMN-s via stimulation of H1 and H3 receptors.

Histamine releasing factor (HRF) in pannus of joints affected by rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that causes chronic infl ammation of connective tissue, primarily in the joints. RA affects the synovial membrane, articular cartilage, fi brous joint capsule and surrounding ligaments and tendons. Over denuded areas of the synovial membrane, granulation tissue called pannus develops. The function of pannus is not known. Histamine and histamine receptors participate in RA pathogenesis [1–3]. Histamine release can be differentially modulated by histamine releasing factor (HRF), which is a cytokine-like molecule playing a pivotal role in various autoimmune diseases. HRF is an intracellular protein which can differentially modulate the secretion of cytokines from human basophils, eosinophils, T cells and B cells, suggesting that it may induce a complex array of responses at sites of allergic infl ammation [4–6]. In this study, we examine the ultrastructure of pannus, expression of HRF mRNA and localization HRF protein in pannus of RA joints.