Screening with monoclonal anti-Fy3 to provide blood for phenotype- matched transfusions for patients with sickle cell disease

BACKGROUND: In the United States, there is a shortage of blood group phenotype-matched red cells (RBCs) for patients with sickle cell disease (SCD). A protocol designed to supply phenotype-matched RBCs for these patients by combining the recruitment of African American blood donors and automated testing of RBCs for these patients for the presumptive Fy(a-b-) phenotype using monoclonal anti-Fy3 was evaluated. STUDY DESIGN AND METHODS: African American donors were recruited, to increase the likelihood of phenotype matches in the donor population. Samples of RBCs were tested for the presumptive Fy(a-b-) phenotype by using monoclonal anti-Fy3 and an automated blood typing analyzer. RBCs confirmed to be Fy(a-b-) were retyped for selected Rh, MNS, Kell, Duffy, and Kidd blood system antigens. The extended phenotypes were matched with those of 41 SCD patients requiring transfusions. RESULTS: Of 8323 blood donations during the study, approximately 40 percent (3329) were made by African Americans. Approximately 22 percent (737) of African Americans were identified as Fy(a-b-) by this protocol and 12 percent (410) were phenotype matches for the 41 SCD patients. CONCLUSION: Combining the recruitment of African American blood donors and automated phenotyping using monoclonal anti-Fy3 offers a practical, relatively low-cost strategy for supplying phenotype-matched RBCs for SCD patients. This protocol increases the options for addressing the shortage of phenotype-matched RBCs for SCD patients.     

A unique therapeutic approach to emesis and itch with a proanthocyanidin-rich genonutrient

Background

We examined the therapeutic potential of a proprietary Croton palanostigma extract (Zangrado^®) in the management of emesis and itch.

Methods

Emesis was induced in ferrets with morphine-6-glucuronide (0.05 mg/kg sc) in the presence of Zangrado (3 mg/kg, ip) and the cannabinoid receptor 1 antagonist, AM 251 (5 mg/kg, ip). Topical Zangrado (1%) was assessed for anti-pruretic actions in the 5-HT-induced scratching model in rats and evaluated in capsaicin-induced gastric hyperemia as measured by laser doppler flow. In the Apc ^Min mouse model of precancerous adenomatosis polyposis, mice received Zangrado (100 μg/ml in drinking water) from the age of 6 – 16 weeks for effects on polyp number. In RAW 264.7 cells Zangrado was examined for effects on lipopolysaccharide-induced nitrite production.

Results

Zangrado was a highly effective anti-emetic, reducing morphine-induced vomiting and retching by 77%. These benefits were not associated with sedation or hypothermia and were not reversed by cannabinoid receptor antagonism. Itch responses were blocked in both the morphine and 5-HT models. Zangrado did not exacerbate the Apc ^Min condition rather health was improved. Capsaicin-induced hyperemia was blocked by Zangrado, which also attenuated the production of nitric oxide by activated macrophages.

Conclusion

Zangrado is an effective anti-emetic and anti-itch therapy that is devoid of common side-effects, cannabinoid-independent and broadly suppresses sensory afferent nerve activation. This complementary medicine represents a promising new approach to the management of nausea, itch and irritable bowel syndrome.

     

蛇毒中鞣花酸类及三萜类成分研究

自蛇毒（ＤｕｃｈｅｓｎｅａｉｎｄｉｃａＦｏｃｋ）全草中分离出６个化合物，其中，２个为新化合物，分别命名为蛇莓甙Ａ（ｄｕｃｈｅｓｉｄｅＡ）和蛇莓甙Ｂ（ｄｕｃｈｅｓｉｄｅＢ），经化学及光谱（ＵＶ，１Ｒ，１ＨＮＭＲ，１３ＣＮＭＲ，ＮＯＥＤＳ和ＭＳ）分析确定，蛇莓甙Ａ的结构为３＇－Ｏ－甲基－鞣花酸－４－Ｏ－β－Ｄ－吡喃木糖甙（Ⅰ），蛇莓甙Ｂ的结构为３＇－Ｏ－甲基－鞣花酸－４－Ｏ－α－Ｌ－呋喃阿拉伯糖甙（Ⅱ）。另外４个化合物为已知三萜类化合物：３β－羟基－乌苏烷－１２－烯－２８－羧酸（Ⅲ），２α，３β，１９α－三羟基－乌苏烷－１２－烯－２８－羧酸（Ⅳ），２α，３β，１９α－三羟基－乌苏烷－１２－烯－２８－羧酸－２８－Ｏ－β－Ｄ－吡喃葡萄糖甙（Ⅴ），２α，３α，１９α－三羟基－乌苏烷－１２－烯－２８－羧酸－２８－Ｏ－β－Ｄ－吡喃葡萄糖甙（Ⅵ）。其中化合物Ⅳ，Ⅴ和Ⅵ为首次从该属植物中分离得到。     

化学—酶法立体控制合成光学纯L-羟基苯丙氦酸的新方法

Optically pure L-3(2-hydroxyphenyl) alanine(L-o-tyrosine ,Ⅲa,),L-3-(3-hydroxyphenyl) alanine(L-m-tyrosine,Ⅲb )and L-3-(4-hydroxyphenyl )alanine(L-p-tyrosine,Ⅲc )were synthesized by the stereocontrolled amination of corresponding hydroxycinnamic acld(Ⅱ)catalyzed by L-phenylalanine ammonia-lyase(PAL,EC4.3.1.5 )contained in Rhodoterula rubramycelium. The amination of compound Ⅱ was completed in aqueous ammonia solution( 6.4mol·L^-1,pH10.5, 30℃) with the conversion of 74.9%(Ⅱa),21.1%(Ⅱb)and 20.6%(Ⅱc)respectively.The absolute configuration of the products Ⅲa～c were confirmed by circular dichroism(CD),and chiral high-performance ligand exchange chromatography(HPLEC)showed that productsⅢ were optically pure L-isomers.