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Biomedical subjects

E Blitstein-Willinger

Publications and source records attributed to E Blitstein-Willinger.

At least 19 recordsLinked to original sources
PubMed1993

Pharmacological activity and local and systemic tolerance of topically applied iloprost.

The chemically stable prostacyclin derivative iloprost (CAS 73873-87-7) infused intravenously induces vasodilation and inhibits platelet aggregation. Numerous clinical studies have shown that iloprost is beneficial in the treatment of obliterative arterial disease. As a topical therapy would have considerable advantages, the pharmacological activity and the tolerance of the drug was evaluated in several studies which included 73 healthy volunteers. The drug was tested in different galenical formulations: aqueous solution, various hydrogels and a fatty ointment. They were applied to intact as well as experimentally damaged (stripped) skin. The pharmacodynamic effects were determined by visual assessment, colorimetry and laser Doppler velocimetry. Moreover, the volunteers were monitored for systemic side effects including changes in blood and urine. After the solution was applied under occlusion, iloprost induced erythema at dose levels of at least 50/25 ng/cm2 (intact/stripped skin). Applied to intact skin, erythema lasted for up to 5 days. When the drug was applied to stripped skin the effect was shorter (24 h). Following low doses, erythema was confined predominantly to the follicles whereas homogeneous redness was induced by higher iloprost doses. Thus penetration seems to occur in particular via the follicles with the horny layer acting as a penetration barrier and as a drug reservoir. High doses (400/150 ng/cm2) induced edema in all cases when applied to intact/stripped skin. When applied to large areas of the skin, increased iloprost serum levels (< or = 80 pg/ml) as well as systemic side effects (inhibition of platelet function, flush, headache) were observed. Tachyphylaxia did not develop after the application of 25 micrograms/100 cm2 once daily for 60 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1992

Inhibition of endotoxin-induced macrophage tumor necrosis factor expression by a prostacyclin analogue and its beneficial effect in experimental lipopolysaccharide intoxication.

Tumor necrosis factor (TNF), a protein produced in large quantities by endotoxin-activated macrophages, has been implicated as an important mediator of the lethal effect of endotoxin. A stable prostacyclin analogue (iloprost) was investigated for its ability to interfere with TNF secretion of lipopolysaccharide (LPS)-stimulated macrophages. It could be demonstrated by bioassays that LPS-induced TNF production was suppressed in a dose-dependent manner when macrophages were treated with iloprost at the time of LPS stimulation. Northern blot analysis revealed that iloprost inhibited TNF production at the transcription level. In vivo, endotoxin-induced mortality rates in galactosamine-sensitized mice could be significantly (P less than .05) reduced by iloprost administration. It is assumed that prostacyclin modulates endotoxin-induced and TNF-mediated inflammation in septic shock.

Animals↗
PubMed1991

Prevention of murine cerebral malaria by a stable prostacyclin analog.

Iloprost, a synthetic prostacyclin analog, successfully prevents the development of cerebral malaria in mice. Malaria antigen-induced tumor necrosis factor (TNF) production could be inhibited by iloprost in vitro and in vivo. Northern analysis of TNF mRNA revealed that malaria antigen-induced TNF expression was suppressed at the transcription level.

Animals↗
PubMed1991

The role of growth factors in wound healing.

Numerous growth factors are involved in the regulation of tissue repair and remodelling processes. The repair process is initiated by inflammation, a phenomenon that is regulated by components of the immune response such as cytokines, matrix elements and growth factors. These locally released growth factors or cytokines induce the recruitment, activation, mitogenesis and differentiation of various other cell types. It is improbable that all of them play a key role in the tissue repair process. Obviously, each of these factors may also influence normal tissue homeostasis. Therefore, the possible use of these factors for therapeutic intervention has to be considered carefully. Some of the important aspects of growth factors with regard to this topic will be discussed.

Animals↗
PubMed1987

Behavior of cutaneous Langerhans' cells and skin reactivity after gold sodium thiomalate treatment of pemphigus vulgaris.

Skin biopsies from pemphigus vulgaris patients in the acute phase of disease and after successful GST therapy were studied in respect to their capacity to express OKT6, OKIa1 and HLA-DR antigens. In comparison to controls, the epidermis overlaying noninvolved skin contained significantly (p = 0.0001) fewer detectable Ia and T6 antigen-bearing Langerhans' cells. Lower epidermal Langerhans' cell density in comparison to controls was detected in both prednisolone-treated and untreated patients. A normalization of prior defective antigen expression was observed in patients in remittence after GST therapy. This correlated with a normal delayed type hypersensitivity reaction (Multitest Mérieux).

Aged↗
PubMed1987

In vitro effects of gold sodium thiomalate on IL-1, IL-2 production, IL-2 receptor expression and IL-2 responsiveness in thymocytes and peripheral blood mononuclear cells.

The aim of this study was to examine the effect in vitro of gold sodium thiomalate (GST) on interleukin 1 (IL-1), and interleukin 2 (IL-2) production and IL-2 receptor expression in thymocytes of mice and in human peripheral blood mononuclear cells (PBMC). GST increased the proliferation of thymocytes and PBMC to suboptimal doses of T cell mitogens Con A and PHA. It induced IL-1 production of the accessory adherent cells within thymocytes and PBMC, IL-1 production in the murine macrophage line P388D1 and induced the PHA reactive thymocytes to produce IL-2 and to express IL-2 receptors. The significance of these findings is discussed.

Animals↗
PubMed1986

[Interleukin 2 deficiency in pemphigus vulgaris].

The synthesis of interleukin-2 (IL-2) has been determined in 5 patients suffering from pemphigus vulgaris. It is well-known that these lymphokine play an important role with regard to the stimulation of lymphocytes. All 5 patients were treated with auric sodium thiomalate (Tauredon) according to Penney. Therapy with corticosteroids had to be reduced or even interrupted because of their numerous side effects. In comparison to the control group, all 5 patients showed decreased synthesis of interleukin-2. Total T-, T-helper, and T-suppressor lymphocytes were measured by immunofluorescence with monoclonal antibodies: The number of T-lymphocytes as well as the ratio of OKT4/OKT8 were normal. We discuss the role of deficient synthesis of IL-2 for the formation of auto-antibodies as well as the effect of gold with regard to modulation of the immune response.

Adrenal Cortex Hormones↗
PubMed1985

Normalization of defective interleukin 1 and interleukin 2 production in patients with pemphigus vulgaris following chrysotherapy.

The aim of this study was to investigate the origins of disturbances of immunoreactivity in patients with pemphigus vulgaris. Peripheral mononuclear blood cells of PV patients showed reduced proliferative responses to lectins in vitro. The capacity of these cells to produce IL-1 and IL-2 was tested. A severe defect in both IL-1 and IL-2 production was observed; in addition, the capacity of the cells to express IL-2 receptors in response to PHA was diminished. The defects did not result from concurrent corticosteroid therapy. The positive therapeutic effect of gold sodium thiomalate therapy correlated with the normalization in the cell's capacity to produce IL-1 and IL-2. It seems possible that the observed deficiencies are related to the pathogenesis of the disease.

Acute Disease↗
PubMed1984

[Therapeutic value of antihistamines today. Dermatoses and allergic diseases of the mucous membranes].

Factors to consider while administering antihistaminic agents: The dosage and time of administration should be related to the expected histamine release or the histamine release which has already taken place. The antihistaminic agents selected for treatment must take a) the type of receptor that is to be blocked (H1, H2), and b) additional pharmacologic properties such as sedation into account. H1-antagonists can be used to treat symptoms of various forms of acute and chronic urticaria, including physical urticaria, cholinergic urticaria and allergic rhinitis. Their indication for allergic forms of bronchial asthma has limitations. Antihistamines suppress the starter function of histamines and therefore, the development of further mediators. Furthermore, they influence the role of histamines in physiologic neurotransmitter processes. The combination of H1- and H2-antagonists can be beneficial in certain cases. Topical application of H1-antagonists leads to an anaesthetising , antipruritic effect and limits vessel permeability. The effect is noticeable after approximately 30 minutes. It is of therapeutical use if applied prior to histamine release.

Administration, Oral↗
PubMed1979

Studies on the relevance of microtubules and of microfilament-dependent processes for triggering lymphocyte activation.

The effects of Isoptin i) on isolated microtubules, ii) on the anti-immunoglobulin and the Concanavalin A induced changes in the plasma membrane topography of murine lymphocytes and iii) on murine lymphocyte activation by lipopolysaccharide and by Concanavalin A was investigated. Isoptin and lidocaine (a local anaestetic) inhibited repolymerisation of tubulin into microtubules and induced depolymerisation of microtubules. Isoptin and lidocaine inhibited competitively binding of colchicine (a classical microtubules disrupting agent) to tubulin. Isoptin induced changes in the plasma membrane topography resembling effects caused by local anaesthetics or by a combination of colchicine and cytochalasin B (an agent affecting microfilament function). Isoptin, lidocaine, colchicine and hydroxyurea when present in the culture medium during the whole incubation period inhibited DNA synthesis induced by lipopolysaccharide or Concanavalin A. RNA synthesis was completely inhibited by lidocaine but not by Isoptin or by colchicine. If Isoptin, colchicine or hydroxyurea were removed from the culture medium at 20 h of culture period, the cells immediately started to incorporate 3H-Thymidine. The inhibitory action of lidocaine was irreversible. These results show that Isoptin, a drug which depolymerizes microtubules in vitro and disturbs the mitogen induced changes in plasma membrane topography of lymphocytes (believed to be controlled by microtubules and microfilaments), does not abolish commitment of the cells for DNA synthesis.

Animals↗
PubMed1978

Inhibition by isoptin (a calcium antagonist) of the mitogenic stimulation of lymphocytes prior to the S-phase.

Isoptin (alpha-isopropyl-alpha-(N-methyl-N-homoveratryl)-gamma-amino-propyl-3,4-dimethoxyphenylacetonitril-hydrochloride)--a calcium antagonist--inhibits mitogenic stimulation of lymphocytes. Isoptin acts prior to the S-phase of the cehl cycle but does not prevent the early events involved in triggering of cell mitosis. The drug seems to be a good tool for studying the relevance of the 'early events' assumed to be involved in lymphocyte stimulation.

Animals↗
PubMed1976

Changes in thymocyte reactivity to lectins induced by B-cell mitogens of the type of sulphated polyanions.

Dextran sulphate, polyvinyl sulphate and carrageenan (but not the other polyanions tested, such as poly I:poly C, poly-L-glutamic acid or E. coli lipopolysaccharide) act synergisticaly with PHA on mouse thymocyte stimulation, as measured by thymidine uptake and blast cell transformation. Furthermore the active compounds shift the dose response of thymocytes to Con A. The effect could be observed in four different strains of mice tested by using normal or cortisone-resistant thymocytes. Two possibilities are envisaged for explanation of these effects: (a) attachment of polyanions by their anionic groups to cell surface constituents and interaction of the sulphate groups of the polymers with plant lectins; and (b) modification of the cell membrane induced by sulphated polymers changing either the binding capacity or the effectiveness of the membrane-associated events leading to thymocyte stimulation by the lectins.

Animals↗
PubMed1976

Suppression of the primary immune response in vivo to sheep red blood cells by B-cell mitogens.

Polyacrylic acid (PAAC), lipopolysaccharide (LPS), dextran sulphate (DS) and purified protein derivative of tubercle bacilli (PPD), compounds mitogenic for B lymphocytes in vitro, suppressed the immune response of mice to SRBC in vivo, when injected 4-2 days before immunization. The same compounds enhanced the immune response when injected half an hour before immunization of the animals with a suboptimal antigen dose. A subsequent injection of PAAC given shortly before immunization, abolished the immunosuppressive effect expected by pretreatment of the animals with either PAAC or LPS. A second injection of LPS abolished the immunosuppressive effect of LPS only. The results indicate that when B lymphocytes react with a mitogen in the absence of a particular antigen, they temporarily lose their capacity to respond to antigen.

Acrylates↗
PubMed1975

Relationship between biological activities of polymers. I. Immunogenicity, C3 activation, mitogenicity for B cells and adjuvant properties.

The effect of thirteen compounds on C3 activation, mitogenicity for B lymphocytes and on the immune response was tested. Only two of the compounds tested, polyinosinic acid and a high molecular weight polyethylenesulphate induced C3 conversion, while eleven out of the thirteen compounds (negative charged immunogenic or non-immunogenic polymers including the three C3 active compounds) stimulated thymidine incorporation in B lymphocytes. The non-charged (T-independent) immunogens dextran and polyvinylpyrrolidone neither activated C3 nor BP lymphocytes. With the exception of single-stranded polyribonucleic acids, the compounds stimulating DNA synthetis in B cells enhanced the response of the mice to a suboptimal dose of sheep red blood cells. In conclusion C3 activation, intrinsic (T-independent) immunogenicity and B-cell stimulation are not correlated properties. However, B-cell mitogenicity and adjuvanticity seem to be related.

Adjuvants, Immunologic↗