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Query: CAS:7440-70-2 (calcium)
 333,191 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is likely that aluminum compounds will continue to be used with human vaccines for many years as a result of their excellent track record of safety and adjuvanticity with a variety of antigens. For infections that can be prevented by induction of serum antibodies, aluminum adjuvants formulated under optimal conditions are the adjuvants of choice. It is important to select carefully the type of aluminum adjuvant and optimize the conditions of adsorption for every antigen since the degree of adsorption of antigens onto aluminum adjuvants markedly affects immunogenicity. The mechanism of adjuvanticity of aluminum compounds includes formation of a depot at the site of injection from which antigen is released slowly; stimulation of immune-competent cells of the body through activation of complement, induction of eosinophilia, and activation of macrophages; and efficient uptake of aluminum-adsorbed antigen particles by antigen-presenting cells because of their particulate nature and optimal size (< 10 microns). Limitations of aluminum adjuvants include local reactions, production of IgE antibodies, ineffectiveness for some antigens, and inability to elicit cell-mediated immune responses especially cytotoxic T-cell responses. Calcium phosphate, which has adjuvant properties similar to aluminum adjuvants, has the potential advantages of being a natural component of the body and of not increasing IgE production. There is a need for alternative adjuvants, particularly for diseases in which cell-mediated immune responses are important for prevention or cure.
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PMID:Adjuvant properties of aluminum and calcium compounds. 755 Dec 19

There are several indications for an involvement of neuroexcitatory mechanisms in ischemic neuron damage. Since we forwarded the hypothesis in 1982 that the transmitter glutamate is playing a key role, several lines of evidence have substantiated this: there is a pronounced transmitter release induced by ischemia and there is uptake of Ca++ via NMDA-operated calcium channels. Under certain circumstances postischemic neuron death can be impaired by administration of either NMDA-antagonists or calcium blockers. Further proof for the induction of harmful excitatory mechanisms by ischemia has been obtained by preischemic denervation of the vulnerable nerve cells. After transient cerebral ischemia in rats or gerbils, there are signs of irreversible damage (eosinophilia) of neurons in the dentate hilus (somatostatin-positive cells) after 2-3 hours and of hippocampal pyramidal neurons after 2-3 days (delayed neuron death). In the first case, removal of the (main) input to hilus cells by degranulation (colchicine selectively eliminates granule cells) protects these. In the case of pyramidal neurons removal of Schaffer collaterals/commisurals or input from the entorhinal cortex have a protective effect. Recently, we have measured glutamate and calcium in CA1 of denervated rats during 10 min of ischemia, and it turns out that there is almost no extracellular glutamate release or lowering of calcium in contrast to ischemic animals with intact innervation. Also in the postischemic period there are indications of a continuation of the damaging processes induced by ischemia. Besides the well known postischemic hypoperfusion, a prolonged release of glutamate has been reported, as well as burst firing in some models.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ischemia as an excitotoxic lesion: protection against hippocampal nerve cell loss by denervation. 838 Jun 75

The authors describe a group of patients where the surgical operation involved among others filling of bone defects with glass-ceramic material--dense (as granules) or porous (as a block). Glass-ceramics BAS O were developed in the laboratories of LASAK Co. in Prague. Two defects were of traumatic origin and osteosynthesis was part of three operations. The remaining defects were juvenile bone cysts, fibrous dysplasia and benign bone tumours. The follow-up period after operation varied in the first 11 patients between 6 months and 2 years. In patients of the mentioned group no problems of healing of the surgical wound were recorded nor allergic and side-reactions. The incorporation of glass-ceramic material was followed up by X-ray after three-months intervals. In no instance lighter areas were found on the X-ray pictures suggesting a fibrous outer layer. On the contrary, the trabeculae reached gradually its close vicinity. Based on experience from experimental work and investigation of X-ray signs of healing, the patients were allowed to burden the operated extremity after three months. The basic laboratory examinations made in these patients were within the normal range. In particular calcium throughout the investigation period in the normal range, the phosphorus levels varied near the upper borderline, alkaline phosphatase levels were in many young patients elevated and acid phosphatases varied. In eight patients during the postoperative period eosinophilia was revealed in the haemogram.
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PMID:[Initial clinical experience with BAS O, a bioactive glass-ceramic material]. 828 13

Eosinophilia in humans is often associated with heart disease and cardiac localization of eosinophil granule proteins, and several results suggest that granule proteins mediate endomyocardial damage. Here we investigated the in vitro effects of the four principal eosinophil granule proteins (eosinophil cationic protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin, and eosinophil peroxidase (EPO)) on the activation of effector cells of inflammation (mast cells) isolated from human heart tissue (HHMC). ECP and, to a lesser extent, MBP (0.3-3 microM), but not eosinophil-derived neurotoxin and eosinophil peroxidase stimulated the release of preformed (histamine and tryptase) and the de novo synthesis of vasoactive and proinflammatory mediators (PGD2) from HHMC. Activation of HHMC by ECP and MBP was Ca2+- and temperature-dependent and was abolished by preincubation (15 min, 37 degrees C) with 2-deoxy-D-glucose (10 mM) and antimycin A (1 microM). There was a significant correlation between the maximal percentage of histamine release induced by ECP and anti-IgE from HHMC (rs = 0.73; p < 0.005), by MBP and anti-IgE (rs = 0.79; p < 0.001), and by ECP and MBP (rs = 0.65; p < 0.005). A positive correlation was also found between histamine and tryptase secretion (rs = 0.71; p < 0.001) and between histamine and PGD2 release induced by ECP from HHMC (rs = 0.85; p < 0.001). This is the first demonstration that some eosinophil cationic proteins, namely ECP and MBP, found at the site of heart damage in patients with eosinophilia, act as complete secretagogues on HHMC. This observation indicates another mechanism by which infiltrating eosinophils and their metabolic products cause inflammatory reactions and thus endomyocardial lesions in patients with eosinophilia.
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PMID:Eosinophil granule proteins activate human heart mast cells. 875 29

Cytokines-in particular interleukin 4 (IL-4), IL-5 and interferon gamma (IFN-gamma)-regulate both IgE synthesis and eosinophil activation in atopic diseases. To elucidate whether distinct profiles of cytokine production were related to serum level of IgE and eosinophilia, the spontaneous and inducible in vitro cytokine secretion from peripheral blood mononuclear cells (PBMC) was investigated. PBMC were isolated and cultured from three groups of donors: (1) patients with atopic dermatitis (AD) and high levels of serum IgE (> 5000 IU/ml, n = 11), (2) patients with diagnosed inhalant allergy (IA) and serum IgE in the range of 200-2000 IU/ml (n = 10), and (3) non-allergic individuals (NA) with serum IgE below 100 IU/ml (n = 10). The production of cytokines was determined in cultures after 24 h [IL-1 alpha, IL-4, IL-5, IL-6, tumour necrosis factor alpha (TNF-alpha), and TNF-beta] or 72 h (IL-2, IFN-gamma). The spontaneous production of IL-1 alpha was increased in the AD group compared to NA (P = 0.002), whereas for unstimulated cultures no other cytokine differed between patient groups. To identify conditions for optimal cytokine production, various combinations of phytohaemagglutinin (PHA), calcium ionophore (ION), and phorbol ester (PMA) were tested as stimuli. The combination ION + PMA induced the highest levels of IL-2, IL-4, IL-5, IFN-gamma and TNF-alpha, whereas maximal production of IL-6 and TNF-beta were induced by PHA and PHA + PMA, respectively. The AD group demonstrated a significantly lower production of TNF-alpha and IFN-gamma compared with the two other groups, and IL-4 and IL-5 production increased in the IA group. The results suggest that in spite of the common features, i.e. raised serum IgE and eosinophilia, in IA and AD patients, the underlying aberrations in the cytokine network is different.
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PMID:Biomolecular regulation of the IgE immune response III. Cytokine profiles in atopic dermatitis, inhalant allergy and non-allergic donors. 889 41

Eosinophilia is often observed in patients with parasitic infections and atopic diseases like allergic asthma and atopic dermatitis. Additionally, it is a typical feature of the inflammatory reaction after therapeutic and accidental exposure to ionizing radiation. This uniquely specific phenomenon regulated by the cytokine interleukin 5 (IL-5) suggests specific control for IL5 gene expression. In this study, we generated promoter-CAT constructs containing different human IL-5 promoter regions spanning from positions -507 to +43. Transfection experiments in Jurkat T cells revealed that the promoter sequence from -57 to +43 was required for constitutive and inducible IL-5 promoter activity. Low baseline CAT activity could be enhanced by treatment with phenylmercuric acetate (PMA) or the combination of PMA and calcium ionophore. The promoter region between positions -97 and +43 showed responsiveness to low-dose X rays. Electrophoretic mobility shift assays demonstrated that the region from -117 to -97 was responsive to irradiation. Transcription factors specifically bound to this sequence showed a dose-dependent response to single doses of X rays between 1 and 8 Gy. Competition analysis indicated that the protein-DNA complexes at this region were related to the nuclear factor of activated T cells (NF-AT). Further confirmation was obtained by the addition of specific antibodies into protein-DNA reactions. For the first time, we have demonstrated that specific DNA binding of NF-ATp at the promoter region from -117 to -97 is involved in transcriptional regulation of the human IL5 gene in response to ionizing radiation.
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PMID:Transcriptional regulation of the human IL5 gene by ionizing radiation in Jurkat T cells: evidence for repression by an NF-AT-like element. 939 98

Inflammation in asthma and other allergic diseases is characterized by excessive production of immunoglobulin E (IgE) and the influx of leukocytes, especially eosinophils. Interleukin 4 (IL-4) and IL-5 are essential for IgE production and eosinophilia, respectively, and are produced by mast cells in allergic conditions, for which glucocorticoids are widely used therapeutically. We assessed the effect of glucocorticoids on IL-4 and IL-5 mRNA production by the RBL-2H3 cell line, an analog of mucosal mast cells. IL-4 and IL-5 mRNAs were induced by an antigen that is used to cross-link receptor bound IgE, by calcium ionophore, or by ionophore with phorbol ester and were markedly inhibited by dexamethasone. In cells activated with ionophore and phorbol ester, 10(-6) M dexamethasone reduced the IL-4 and IL-5 mRNA levels to only 12.8 and 5.7%, respectively, of those in cells without dexamethasone, and 10(-9) M dexamethasone caused reductions to 27 and 56%, respectively. Hydrocortisone at 10(-6) and 10(-7) M almost completely inhibited IL-4 and IL-5 mRNA production. Dexamethasone was markedly inhibitory even if it was added after the cells were activated, provided that it was present in the cultures for at least 1.5 h. These studies indicate that the expression of IL-4 and IL-5 mRNAs by mast cells is highly sensitive to glucocorticoids. The data suggest that these inhibitory effects may contribute to the clinical efficacy of glucocorticoids in the therapy of allergic diseases.
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PMID:Induction of interleukin-4 and interleukin-5 expression in mast cells is inhibited by glucocorticoids. 945 73

The association between the onset of eosinophilic fasciitis and exposure to a drug or a toxin has occasionally been reported. We describe 3 patients who developed eosinophilic fasciitis a few months after they received subcutaneous calcium heparin. In 2 patients, clinical manifestations and eosinophilia improved after interruption of the therapy. Although spontaneous occurrence of eosinophilic fasciitis cannot be excluded in our patients, the temporal relationship with the beginning of subcutaneous heparin therapy raises the possibility that the syndrome might be precipitated by the drug.
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PMID:Possible association between eosinophilic fasciitis and subcutaneous heparin use. 948 39

Eosinophils are prominent inflammatory cells which play a critical role in the pathogenesis of allergic diseases and bronchial asthma. The aim of this experiment was to examine the effects of oxatomide (CAS 60607-34-3, KW-4354), an antiallergic agent, on oxygen-radical generation and peptide-leukotriene (p-LT) release from guinea pig eosinophils. Ketotifen (CAS 345080-13-7) and epinastine (CAS 80012-43-7) were used as reference drugs. Eosinophils were isolated from the peritoneal exudate of guinea pigs, in which peritoneal eosinophilia had been induced by injection of horse serum. Oxygen-radicals were measured with luminol-dependent chemiluminescence and p-LT release was measured with enzyme immunoassay. When eosinophils were stimulated with phorbol miristate acetate, oxatomide and ketotifen inhibited the oxygen-radical generation with a concentration required for 50% inhibition (IC50) of 11.7 mumol/l and 28.4 mumol/l. Oxatomide, ketotifen or epinastine showed an inhibition of oxygen-radical generation induced by calcium ionophore A-23187 and the IC50 value was 11.3 mumol/l for oxatomide, 15.1 mumol/l for ketotifen and 27.3 mumol/l for epinastine, suggesting that oxatomide is a more potent inhibitor of oxygen-radical generation than ketotifen and epinastine. Oxatomide also inhibited p-LT release induced by calcium ionophore A-23187 (IC50, 9.83 mumol/l). Ketotifen and epinastine only weakly inhibited p-LT release. These results suggest that oxatomide may regulate inflammatory diseases, such as bronchial asthma, through suppression of eosinophil function.
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PMID:Inhibitory effect of oxatomide on oxygen-radical generation and peptide-leukotriene release from guinea pig eosinophils. 952 30

Within 10 minutes of intraperitoneal injection of penitrem A (3 mg/kg), rats develop severe generalized tremors and ataxia that persist for up to 48 hours. These are accompanied by a three- to fourfold increase in cerebellar cortical blood flow. Mitochondrial swelling occurs in cerebellar stellate and basket cells within 30 minutes of dosing and persists for more than 12 hours without leading to cell death. From 2 hours, Purkinje cell dendrites show early cytoplasmic condensation accompanied by fine vacuolation of smooth endoplasmic reticulum and enlargement of perikaryal mitochondria. From 6 hours, many Purkinje cells develop intense cytoplasmic condensation with eosinophilia that resembles "ischemic cell change," and from 12 hours, many other Purkinje cells show marked watery swelling. Astrocytes begin to swell from 0.5 hours after injection and show hypertrophy of organelles from 6 hours. Also from 6 hours onward, discrete foci of necrosis appear in the granule cell layer, while permeability of overlying meningeal vessels to horseradish peroxidase becomes evident at 8 hours. All changes are more severe in vermis and paravermis. Despite widespread loss of Purkinje cells, the animals' behavior becomes almost normal within a week. While tremor occurs with doses of 1.5 and 0.5 mg/kg, cellular damage is minimal. The tremor mechanism differs from that of harmaline since destruction of inferior olivary nuclei abolishes neither the tremor response to penitrem A nor the cellular damage. No morphological changes are found in other brain regions. The affinities of penitrem A for high-conductance calcium-dependent potassium channels and for gamma-aminobutyric acid receptors with the probability of resultant excitotoxity are considered to be important underlying factors for these changes.
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PMID:The effects of the tremorgenic mycotoxin penitrem A on the rat cerebellum. 954 35


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