华北白前中的新三萜成分

从华北白前(Cynanchum hancockianum)中分离到4个新三萜类化合物,通过光谱分析(¹HNMR,¹³CNMR,2DNMR,MS,X-Ray)及化学相关等分别鉴定为华北白前醇(hancockinal,Ⅰa).新自前醇(hancolupenoI,Ⅱd),新白前酮(hancolupenone,Ⅱc)及新白前醇二十八烷酸酯(hancolupenol octacosanate,Ⅱd),均为新型骨架的化合物。     

Occipital involvement in female pattern hair loss: histopathological evidences

Background Female pattern hair loss (FPHL) is characterized by diffuse thinning of hair in the frontal and parietal areas of the scalp, and preservation of the frontal hairline is the norm. Hair on the occipital scalp is thought to be preserved. Objective To investigate whether the occipital area is involved in FPHL or whether there is a diffuse type of FPHL. Methods Forty female patients who had complained about hair loss for more than a year and were diagnosed with FPHL according to the Ludwig classification were included. Two punch biopsies from both the midscalp and the occiput were taken. Histological sections were prepared horizontally and stained with haematoxylin and eosin. Terminal follicles, vellus like follicles, anagen, telogen, catagen follicles, hair bulbs and telogen germinal units were counted in two sections of the upper dermis and the dermal‐subcutaneous junction. If the terminal/vellus ratio was lower than 4:1, the diagnosis of androgenetic alopecia (AGA) was made. When the ratio was between four and seven to one, AGA was suspected. Results While 29 of 40 patients (72.5%) had findings consistent with AGA on the midscalp, 11 of 40 (27.5%) displayed signs of suspected AGA. Ten of 40 patients (25%) had AGA involving the occiput. Conclusion The involvement of the occipital scalp is significant in FPHL. In some patients, this situation may be so apparent that clinically visible alopecia is seen. However, in other patients, it may also present only as thinning.     

Steroids and related studies: Part 88-3-(2-dialkylaminoethoxy)-17α-methyl-17α-aza- -homo-1,3,5(10)-estratriene dimethiodides

Three of the title compounds 15, 16 and 17 were prepared as potential neuromuscular blocking agents. Structurally these partly resemble clinically active chandonium iodide (1). In the in vivo tests, all three compounds were less active than chandonium; however, compounds 16 and 17 were more active in in vitro testings. While preparing the bisquaternary compounds, different steroidal amines were obtained, the hydrochlorides of which when tested showed no significant antiarrhythmic activity.     

In vitro and in vivo characterization of A-940894: a potent histamine H4 receptor antagonist with anti-inflammatory properties

Background and purpose:

The histamine H₄ receptor is widely expressed in cells of immune origin and has been shown to play a role in a variety of inflammatory processes mediated by histamine. In this report, we describe the in vitro and in vivo anti-inflammatory properties of a potent histamine H₄ receptor antagonist, A-940894 (4-piperazin-1-yl-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-ylamine).

Experimental approach:

We have analysed the pharmacological profile of A-940894 at mouse native, rat recombinant and human recombinant and native, histamine H₄ receptors by radioligand binding, calcium mobilization, mast cell shape change, eosinophil chemotaxis assays and in the mouse model of zymosan-induced peritonitis.

Key results:

A-940894 potently binds to both human and rat histamine H₄ receptors and exhibits considerably lower affinity for the human histamine H₁, H₂ or H₃ receptors. It potently blocked histamine-evoked calcium mobilization in the fluorometric imaging plate reader assays and inhibited histamine-induced shape change of mouse bone marrow-derived mast cells and chemotaxis of human eosinophils in vitro. In a mouse mast cell-dependent model of zymosan-induced peritonitis, A-940894 significantly blocked neutrophil influx and reduced intraperitoneal prostaglandin D₂ levels. Finally, A-940894 has good pharmacokinetic properties, including half-life and oral bioavailability in rats and mice.

Conclusions and Implications:

These data suggest that A-940894 is a potent and selective histamine H₄ receptor antagonist with pharmacokinetic properties suitable for long-term in vivo testing and could serve as a useful tool for the further characterization of histamine H₄ receptor pharmacology.