Research Progress of Gypsum Ustum and Application of Calcium-containing Hemostatic Materials / 中国实验方剂学杂志

Mineral medicine is an indispensable part of traditional Chinese medicine and has a long history of application. Among them， mineral-based hemostatics have been widely applied for the treatment of various hemorrhagic diseases with extensive clinical experience and established efficacy. Gypsum Fibrosum （GF）， a commonly used mineral medicine in clinical， can clear away heat， and relieve anxiety and thirst. Gypsum Ustum （GU） is the processed product of GF after calcining at high temperature. It is mainly composed of anhydrous calcium sulfate （CaSO4） with the functions of moisturizing， promoting muscle growth， astringent sores and hemostasis. GU is often used externally to treat ulcer， itching， eczema， water and fire scalds， trauma bleeding， etc. Studies on the mechanism of hemostasis have shown that Ca2+ （coagulation factor Ⅳ） is involved in many key processes of the internal and external coagulation cascades and can prevent bleeding by regulating platelet activation and aggregation， and promoting the production of insoluble fibrin and the ultimate formation of a blood clot. GF and GU both contain Ca2+ which provide an important material basis of hemostatic effect for both compounds， but GU has a significant hemostatic effect， while GF has no hemostatic effect. After processing， the taste and efficacy of the GF have been obviously changed which reflects the characteristics of processing， but the processing mechanism of GU has not been fully clarified. Therefore， based on studies of GF before and after calcining， this paper focused on these aspects including calcining process， crystal form comparison， element content， efficacy comparison， and summarized various aspects of Ca2+ involved in hemostasis. In addition， the hemostatic properties of other calcium-containing mineral medicines and new calcium-containing hemostatic materials such as calcium alginate， mesoporous calcium silicate and nanogel hemostatic materials were also discussed. The paper aimed to provide a reference for elucidating processing mechanism and clinical dialectical use of GU， also to promote development of new calcium-containing hemostatic materials.

Comparative Studies on Anti-thrombin Activity and Anticoagulant Mechanism between Whitmania Pigra Whitman and Hirudinaria Manillensis / 中国药师

Objective:To compare the anti-thrombin activity and the effects on the coagulation pathway between Whitmania pigra Whitman and Hirudinaria manillensis to provide scientific reference for the anticoagulation mechanism revelation for Hirudo. Methods:Anti-thrombin titration and chromogenic substrate assay-extraction-HPLC were applied to study the anti-thrombin activity of Whitmania pigra Whitman and Hirudinaria manillensis. APTT, PT and TT were determined by a clotting assay to compare the effects on the path-way of blood clotting. Results:The anticoagulation activity order measured by anti-thrombin titration was living Hirudinaria manillensis> dried Hirudinaria manillensis > > dried Whitmania pigra Whitman. The results of chromogenic substrate assay-extraction-HPLC in-dicated that the low dose of aqueous extract promoted the thrombin activity, while the high dose inhibited the thrombin activity. Hirudi-naria manillensis significantly inhibited the activity of thrombin, while Whitmania pigra Whitman showed weak anti-thrombin activity only at the higher dose. All leeches could prolong APTT, PT and TT. However, living Hirudinaria manillensis mainly affected TT, and dried Hirudinaria manillensis mainly affected APTT. Dried Whitmania pigra Whitman dramatically influenced APTT and TT. All the results indicated that the anticoagulant activity of Whitmania pigra Whitmanis was significantly higher than that of Hirudinaria manillen-sis. Conclusion:There are notable differences in the anti-thrombin activity and the effect on the pathway of blood clotting between Whitmania pigra Whitman and Hirudinaria manillensis.

rTFPI reduces ischemic necrosis in random pattern skin flap avulsion injuries rat model / 中华显微外科杂志

Objective To determine whether rTFPI could inhibit vascular thrombosis and salvage random pattern skin flaps following AIRC in rat models.Methods From April,2013 to June,2015,30 adult male Sprague-Dawley rats were randomized into 3 groups;a control group,an avulsion injury with roll compaction (AIRC) group,and an AIRC plus rTFPI therapy group.An 8.0 cm× 2.5 cm random flap was raised on the dorsum of each rat.The AIRC and AIRC plus rTFPI flaps were then altered with a device designed to simulate avulsion injury with roll compaction.After flap closure primarily,treatment was initiated immediately and continued for 3 days.Phosphate buffered saline was used in the control group and the AIRC group,while the AIRC plus rTFPI group received the recombinant Tissue Factor Pathway Inhibitor.Laser Doppler flowmetry and infra-red thermalgraphy were used on postoperative day three to assess nicrocirculatory blood flow and viability of the avulsed flaps.At postoperative day seven,final flap survival was determined.Using SPSS19.0 statistical analysis.Results The flap survival in AIRC group was only (32.7 ± 5.2)％ versus (62.5 ± 6.5)％ in control group,but the flap survival significantly increased (51.6 ± 8.2)％ after topical injecting rTFPI in experimental group.Statistically significant differences exist (P ＜ 0.05) between every two groups.The detection results of Laser-Doppler flowmetry and infra-red thermography showed that perfusion arrived the centre of the flaps in experimental group,while perfusion only arrived the proximal part of the flaps in the AIRC control group.Conclusion rTFPI therapy is effective in reducing ischemic necrosis of random pattern flaps following avulsion injury in the rat model.It suggests that rTFPI therapy may play an important role in clinical salvage of the failing avulsion injuries with roll compaction.

Activation of the Intrinsic Coagulation Pathway in Patients With Chronic Urticaria

PURPOSE: Although coagulation activation has been reported in chronic urticaria, data pertaining to detailed changes in coagulation factors and global coagulation status are lacking. The current study evaluated global coagulation status in patients with chronic urticaria using thrombin generation assay (TGA) and the levels of individual coagulation factors. METHODS: Patients with chronic urticaria (n=57) and 20 healthy controls were enrolled. TGA was performed under stimulation with 2 concentrations of tissue factor (TF). Coagulation factors and conventional coagulation assays were also analyzed. RESULTS: Although patients with chronic urticaria showed prolonged activated partial thromboplastin time, prothrombin time did not differ significantly between patients and controls. In both 1 pM and 5 pM TF-stimulated TGA, peak thrombin and endogenous thrombin potential (ETP) levels were markedly decreased in patients with chronic urticaria. As expected, intrinsic coagulation factors (VIII, IX, and XII), as well as coagulation factors of the common pathway (II, V, and X), were consistently decreased. Additionally, D-dimer was significantly increased in patients as compared to controls. In multivariate regression analysis, the presence of chronic urticaria was the only significant independent contributor to the low ETP value. CONCLUSIONS: Chronic urticaria is characterized by in vivo coagulation activation through the intrinsic coagulation pathway, which can be measured with sensitivity using TGA.

Correlation between plasma D-dimer levels and the severity of patients with chronic urticaria

BACKGROUND: Beside autoimmunity, coagulation pathway is also involved in the pathogenesis of chronic urticaria (CU). Previous studies showed that plasma D-dimer levels paralleled the severity of the disease. To date, there are no data concerning D-dimer level in Thai patients with CU. OBJECTIVE: This study aimed to find the relationship between plasma D-dimer levels and the disease severity of Thai CU patients. The secondary objective is to analyze plasma D-dimer level in each group of patients who performed autologous plasma skin testing (APST) and autologous serum skin testing (ASST). METHODS: We retrospectively reviewed case record forms of chronic idiopathic urticaria (CIU) patients aged at least 18 years in Skin Allergy Clinic, Siriraj Hospital Mahidol University, Bangkok, during June 2008 to June 2011. RESULTS: Of 120 patients, plasma D-dimer level was abnormal in 58 patients (48.3%). The study showed statistically significant positive correlation between disease severity and plasma D-dimer level (p < 0.05, r = 0.537). There was no statistically significant difference in plasma D-dimer level between APST positive and negative groups, and also between ASST positive and negative groups. In APST negative group, plasma D-dimer level was elevated in 29 patients (47.5%) and correlated with disease severity. CONCLUSION: This study showed elevated plasma D-dimer levels in nearly half of Thai patients with CIU. There was a positive correlation between plasma D-dimer levels and the severity of disease activity. Investigation for plasma D-dimer level may be an alternative way to evaluate disease severity in patients with CIU.