Stimulation of histamine synthesis in rat mast cells by compound 48/80 in vitro

Summary The histamine content of rat peritoneal fluid cells is doubled within 20 min by 0.5 g/ml of compound 48/80. Histamine catabolism inhibitors do not reproduce this effect; cells pre-incubated with -fluoromethylhistidine are unresponsive to compound 48/80 which therefore activates pre-formed histidine decarboxylase rather than inducing it. Non-mast cells showed no change after treatment with compound 48/80.     

Die Leucinaminopeptidaseaktivität des Rattenharnes nach Verabreichung einer mastzellerschöpfenden Substanz

Summary LAP activity was determined in rat urine under normal conditions and following mast cell depletion by compound 48/80. A statistically significant increase in urinary LAP activity is found after administration of compound 48/80. This increase is due to mast cell depletion and the resulting anaphylactoid reaction.     

Radiation-released histamine in the rhesus monkey as modified by mast-cell depletion and antihistamine

Summary 4000 rads of mixed gamma neutron radiation administered to rhesus monkeys released a significant amount of histamine into their circulation. When the monkeys were treated with a mast-cell histamine depleter (compound 48/80) for 4 days and then irradiated, no increase in circulating histamine was seen. When 48/80 was given 20 min after irradiation, only a slight increase in histamine was seen, indicating that 4000 rads had released most of the mast-cell histamine.     

Radiation-released histamine in the rhesus monkey as modified by mast-cell depletion and antihistamine.

4000 rads of mixed gamma neutron radiation administered to rhesus monkeys released a significant amount of histamine into their circulation. When the monkeys were treated with a mast-cell histamine depleter (compound 48/80) for 4 days and then irradiated, no increase in circulating histamine was seen. When 48/80 was give 20 min after irradiation, only a slight increase in histamine was seen, indicating that 4000 rads had released most of the mast-cell histamine.     

Die Aktivität der alkalischen Phosphatase im Rattenharn nach Mastzelldegranulierung

Summary Alkaline phosphatase activity was determined in rat urine under normal conditions (80 animals) and following mast cell depletion (30 animals). A statistically significant increase in urinary APA was found after administration of the mast-cell depleting compound 48/80. This fourfold increase over normal activity is due to renal changes caused by shock.     

Thermal effects from degranulation of mastcells in cutaneous mastocytosis

Summary Small biopsies of the skin were taken from patients with papulo-cutaneous mastocytosis. The mast cell tumours were then degranulated with compound 48/80 (250 g/ml in saline), and with a Sorption microcalorimeter, relatively strong exothermic reactions were measured, whereas normal skin showed only 1/10th the intensity. Disodium chromoglicate (1%) had no inhibitory effect on this thermal reaction.     

Die alkalische Phosphatase-Aktivität des Ratten-serums nach anaphylaktoidem Schock

Summary At seven different intervals after the elicitation of anaphylactoid shock (compound 48/80), determinations of alkaline phosphatase (AP) activity were carried out in rat serum. No significant increase could be detected. These findings exclude extrarenal factors as the cause for increased AP-activity in urine following anaphylactoid shock.     

Degranulating activity in hybrid cells derived from rat peritoneal mast cells and ehrlich ascites tumor cells

Summary Fusion of rat mast cells and Ehrlich ascites tumor cells was mediated by HVJ. Compound 48/80-induced degranulation occurred in the fused cells formed from two mast cells and one tumor cell, but not in the fused cells from one mast cell and two or more tumor cells.I am grateful to DrK. Utsumi for valuable discussions and for the donation of HVJ.     

Effect of the mast cell disruptor B.W. 48/80 on dietary atherosclerosis in the male rabbit

Zusammenfassung Mit Cholesterin ernährte Kaninchen, denen gleichzeitig Compound 48/80 injiziert wurde, wiesen gegenüber nur mit Cholesterinzusatz gefütterten Tieren geringere Atheromatose des Aortenbogens auf. Compound 48/80 rief auch eine Verminderung des Serumcholesteringehaltes hervor. Unter dem Einfluss von Compound 48/80 schien ein beschleunigter Abbau der atheromatösen Plaques einzusetzen bevor noch eine Verminderung des Serumcholesterins auftrat. Es wird vermutet, dass der Schutz von Compound 48/80 gegen die durch Diät erzeugte Atheromatose des Kaninchens auf einer Veränderung des arteriellen Glykosaminglykans beruht.     

Histaminantagonistische Wirkungen von Adrenochrom-Monosemicarbazon

Summary In experiments on the skin of the guinea pig, the monosemicarbazone of adrenochrome is shown to prevent increase of vascular permeability due to intradermal injection of histamine or endogenous histamine liberating substance 48/80. By simultaneous intradermal injection with histamine or 48/80, it is equally effective as specific antihistamines in suppressing the skin reaction to 48/80, whereas the antihistamines are considerably stronger antagonists to exogenous histamine. Administered intraperitoneally, adrenochrome monosemicarbazone shows about the same order of antagonistic efficacy as the typical antihistamines. The findings are briefly discussed.

---

---

« Adrenoxyl » ORION Helsinki, unter Lizenz LABAZ Brüssel.     

Compound 48/80 decreases adenosine 3′5′-monophosphate formation in rat peritoneal mast cells

Zusammenfassung Präparat 48/80 unterdrückt die Bildung von 3,5-AMP aus Adenin in isolierten peritonealen Mastzellen. Es konnte keine zeitliche Verschiebung zwischen dieser Unterdrückung und der Histamin freisetzenden Wirkung von Präparat 48/80 festgestellt werden.

---

---

This investigation was supported by United States Public Health Service Grant GM 13016 from the National Institute of General Medical Sciences.     

Immunomodulating effects in vitro of a hydroxythiazolobenzimidazole in the absence of mitogenicity

Wy-13, 876, a hydroxythiazolobenzimidazole, enhanced in vitro antibody formation by mouse spleen cells immunized with sheep red blood cells. The optimal dose was 25--50 microgram/culture. The compound did not have a mitogenic effect at any dose.     

Über die Bindung von Kallidin an Heparin

Summary Kallidin gives, with heparin, a non-dialysable complex, which can be precipitated with alcohol. In this binding, kallidin is pharmacologically active, but may be split off by the substance 48/80.     

Immunomodulating effects in vitro of a hydroxythiazolobenzimidazole in the absence of mitogenicity

Summary Wy-13, 876, a hydroxythiazolobenzimidazole, enhanced in vitro antibody formation by mouse spleen cells immunized with sheep red blood cells. The optimal dose was 25–50 g/culture. The compound did not have a mitogenic effect at any dose.     

Modulation of natural killer cell cytotoxicity and cytokine release by the drug glatiramer acetate

Glatiramer acetate (GA or Copaxone) is a drug used to treat experimental autoimmune encephalomyelitis in mice and multiple sclerosis in human. Here, we describe a new mechanism of action for this drug. GA enhanced the cytolysis of human NK cells against autologous and allogeneic immature and mature monocyte-derived dendritic cells (DCs). This drug reduced the percentages of mature DCs expressing CD80, CD83, HLA-DR or HLA-I. In contrast, it did not modulate the percentages of NK cells expressing NKG2D, NKp30, or NKp44. Nonetheless, anti-NKp30 or anti-CD86 inhibited GA-enhanced human NK cell lysis of immature DCs. Hence, CD86, and NKp30 are important for NK cell lysis of immature DCs, whereas CD80, CD83, HLA-DR and HLA-I are important for the lysis of mature DCs when GA is used as a stimulus. Further, GA inhibited the release of IFN-γ 24 h but increased the release of TNF-α 48 h after incubation with NK cells. Received 13 November 2008; received after revision 10 February 2009; accepted 18 February 2009     

Renale Enzymausscheidung im anaphylaktoiden Schock nach Verabreichung vonge-Aminocapronsäure

Summary In rats pretreated with-amino-caproic acid urinary leucine aminopeptidase (LAP) and alkaline phosphatase (AP) activities were determined following anaphylactoid shock (Compound 48/80). Both enzymatic activities were found to be increased, the increase measuring 110% in AP and 80% in LAP. The values obtained were much lower than in rats without antifibrinolytic treatment. The significance of this finding is briefly discussed.     

Nephrectomy and anaphylactoid edema

Zusammenfassung Nephrektomie hemmt bei Ratten die Ausbildung des lokalen sowie des generalisierten Anaphylaktoid-Ödems erheblich. Die Wirkung der lokal injizierten Substanz 48/80 wird ebenfalls gehemmt, während der Effekt des in die Pfote verabreichten Serotonins unverändert bleibt. Insulin antagonisiert den Hemmungseffekt der Nephrektomie.     

氧化苦参碱对人宫颈癌SiHa细胞株增殖及凋亡的影响

目的研究氧化苦参碱对体外人宫颈癌SiHa细胞株增殖活性及凋亡的影响。方法对人宫颈癌SiHa细胞株进行体外培养,经氧化苦参碱处理的细胞组为实验组,未经处理组为对照组。采用MTT细胞存活实验检测氧化苦参碱对入宫颈鳞癌SiHa细胞的增殖影响,并计算IC50;倒置相差显微镜下观察不同浓度的氧化苦参碱作用48h后SiHa细胞的形态改变;Hoechst33258染色法和Western blot法检测氧化苦参碱对SiHa细胞核及凋亡相关蛋白(P53、Bax及Bcl-2)表达水平的影响。结果 MTT结果显示氧化苦参碱剂量-时间依耐性抑制人宫颈癌SiHa细胞的体外增殖(P0.05),计算24 h、48 h和72 h的IC50分别为(1 028.41±3.57)μg/ml、(701.72±6.01)μg/ml和(406.88±2.15)μg/ml;氧化苦参碱处理48 h后,SiHa细胞的形态特征及数目发生显著变化,且随氧化苦参碱浓度的增加而愈加明显;Hoechst33258染色证实氧化苦参碱处理后SiHa细胞发生凋亡,可见典型的凋亡特征;Western blot结果证实氧化苦参碱(700μg/ml、1 600μg/ml)处理48 h后,和对照组比较,药物处理组细胞凋亡周期蛋白P53、Bax表达上调(P0.05),而Bcl-2表达下调(P0.05),Bax/Bcl-2的比率明显增加(P0.05)。结论氧化苦参碱可抑制体外人宫颈癌SiHa细胞的体外增殖活性发挥其抗肿瘤作用,其作用机制可能诱导SiHa细胞的凋亡有关。     

Selective incorporation of zinc into rat mast cells

Zusammenfassung Bei der Albinoratte findet sich 48 h nach parenteraler Verabreichung von radioaktivem Zink (Zn⁶⁵) ein hoher Anteil der Aktivität in den Gewebemastzellen. Nach Verabreichung des chemischen Histaminliberators, Compound 48/80, wird ein erheblicher Teil von Zn⁶⁵ aus den Zellen frei.

---

---

This work was supported by the Schweizerische Nationalfonds zur Förderung der wissenschaftlichen Forschung (Grant No. 5200.3).