作者: Ito, Tadashi ; Osanai, Yasuo ; Imaizumi, Takahito ; Yamada, Yasushi ; Azuma, Hiroshi ; Miyamoto, Rina ; Yamada, Tetsuya ; Ishida, Tatsuhiro ; Soga, Takaomi ; Kure, Tomoko ; Sakai, Hiromi ; Ogawa, Makoto ; Shimizu, Taro ; Kobayashi, Naoko ; Ando, Jiro

The safety and efficacy of hemoglobin vesicles (HbVs) as artificial oxygen carriers encapsulating a purified and concentrated Hb solution in liposomes have been studied extensively. The HbV surface, modified with PEG by incorporating a PEG-conjugated phospholipid, is beneficial for storage and biocompatibility. However, it might be possible that interaction of PEG and the pre-existing anti-PEG antibody in the bloodstream causes acute adverse reaction. This study used two sets of experiments with rats and guinea pigs to ascertain whether the anti-PEG antibody generated by the PEG-modified HbV injection can induce anaphylactic reactions. SD rats received repeated intravenous injection of HbV at a dose rate of 16 or 32 mL/kg three times. Not anti-PEG IgG but anti-PEG IgM was detected. Nevertheless, no anaphylactic reaction occurred. Guinea pigs were used to study the presence of active systemic anaphylaxis further after injections of the PEG-modified liposomes used for HbV. The animals were sensitized by three repeated subcutaneous injections of PEG-modified liposomes (PEG-liposome) along with adjuvant at 1 week intervals. For comparison, unmodified liposomes (liposome) and 10 times excessively PEG-modified liposomes with ionizable lipid (10PEG-DODAP-liposome) were used. Inclusion of PEG modification induced not only anti-PEG IgM but also anti-PEG IgG. Three weeks after the final injection, intravenous injection of both PEG-liposome and liposome (1 mL/kg) induced no anaphylactic reaction. However, the injection of 10PEG-DODAP-liposome showed one lethal anaphylaxis case and one mild anaphylaxis case. Antisera obtained from the animal sensitized as described above were inoculated (0.05 mL) intradermally into fresh guinea pigs. The presence of passive cutaneous anaphylaxis was evaluated after intravenous injections (1 mL/kg) of three liposomes with Evans blue. No dye leakage was detected at any inoculated skin point for PEG-liposome or liposome, but a slight leakage was detected in one inoculated skin point for 10PEG-DODAP-liposome. These results indicate the absence of acute allergic reactions at repeated injections of HbVs despite the anti-PEG antibody induction. Not all the PEG-modified liposomes show anaphylaxis, and it may depend on the amount of PEGylated phospholipid and lipid composition of PEG-modified liposomes.

2023-09-04·Molecular pharmaceutics

Research Progress in Oxygen Carrier Design and Application.

Review

作者: Zheng, Deyuan ; Chen, Kaiyuan ; Ye, Qingsong ; Wu, Jinhui

Ischemia or hypoxia can lead to pathological changes in the metabolism and function of tissues and then lead to various diseases. Timely and effective blood resuscitation or improvement of hypoxia is very important for the treatment of diseases. However, there is a need to develop stable, nontoxic, and immunologically inert oxygen carriers due to limitations such as blood shortages, different blood types, and the risk of transmitting infections. With the development of various technologies, oxygen carriers based on hemoglobin and perfluorocarbon have been widely studied in recent years. This paper reviews the development and application of hemoglobin and perfluorocarbon oxygen carriers. The design of oxygen carriers was analyzed, and their application as blood substitutes or oxygen carriers in various hypoxic diseases was discussed. Finally, the characteristics and future research of ideal oxygen carriers were prospected to provide reference for follow-up research.

2023-01-01·Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES

Evaluation of the relationship between Hemoglobin, Albumin, Lymphocyte, Platelet (HALP) score and treatment modality and mortality in patients with ileus

Article

作者: Atiş, Şeref Emre ; Günaydın, Yahya Kemal ; Çekmen, Bora ; Bildik, Büşra ; Dorter, Melis

AMAÇ: İleus, bağırsak geçişinin tıkanması olarak tanımlanan ve bağırsaklarda mekanik obstrüksiyon veya paralitik nedenlere bağlı olarak gelişen klinik durumdur. İnce bağırsak obstrüksiyonları primer olarak cerrahi durumlar olarak anılsada, konservatif tedavi bazı hastalarda seçilen bir tedavi protokolüdür. Bu çalışmanın amacı, ileus hastalarında HALP skorunun konservatif-cerrahi tedavi kararını, mortaliteyi ve hastanede kalış süresini belirlemede efektivitesini ve enflamasyonla ilişkili diğer parametrelere üstünlüğünü değerlendirmektir. GEREÇ VE YÖNTEM: Çalışmaya ileus tanısı alan hastalar dahil edildi. Yaş, cinsiyet, komorbiditeler, seçilen tedavi yöntemi (konservatif veya cerrahi), hastanede kalış süresi ve hastane içi mortalite kaydedildi. Biyokimya parametrelerinden beyaz kan hücresi, hemoglobin, trombosit, nötrofil, lenfosit, nötrofil, lenfosit, üre, kreatinin, aspartat aminotransferaz, bilirubin, albümin ve C-reaktif protein seviyeleri kaydedildi. HALP skoru hesaplandı ve mortalite, hastanede kalış süresi, konservatif ve cerrahi tedavi kararı arasındaki ilişki analiz edildi. BULGULAR: Çalışmaya toplam 286 hasta alındı. 245 (%85.7) hastada konservatif tedavi uygulandı. 262 (%91.6) hastada mortalite izlenmedi, 24'ünde (%8.4) mortalite izlendi. HALP skoru mortalite izlenmeyen hastalarda anlamlı olarak yüksekti (p=0.045). Mortalite izlenmeyen hastaların medyan albümin değeri mortalite izlenen hastalardan daha düşüktü (p<0.001). Mortalite izlenen hastaların yaş, üre, kreatinin, AST ve CRP değer-leri, izlenmeyenlere göre anlamlı olarak daha yüksekti (sırasıyla, p=0.002, p<0.001, p<0.001, p<0.001, p<0.001 ve p=0.001). Konservatif tedavi uygulanan hastaların HALP skoru, cerrahi tedavi uygulananlara göre anlamlı olarak yüksekti (p=0.003). Lenfosit değeri konservatif tedavi ile izlenen hastalarda anlamlı olarak yüksekti (p=0.027). Ameliyat olan hastalarda yaş, üre, kreatinin ve CRP skorları daha yüksekti (sırasıyla, p=0.007, p<0.001, 0.003 ve p<0.001). Tedavi yöntemi ve HALP skoru için ROC analizi yapılıp HALP skoru 28 olarak alındığında konservatif tedaviyi saptamada du-yarlılık 50.6%, özgüllük 78.0%, pozitif LR 2.3 ve negatif LR 0.63 olarak tespit edildi. (EAA 0,645 [%95 güven aralığı = 0.556-0.735) ]; p=0.003). SONUÇ: HALP skoru ileuslu hastalarda mortalite ve tedavi şeklinin belirlenmesinde faydalı olabilecek önemli bir skorlama sistemidir. HALP skoru-nun ileus tanılı hastaların yönetiminde, hem mortaliteyi azaltmada hem de uygun tedavi yöntemini belirlemede olumlu katkı sağlayacağı kanaatindeyiz.

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适应症	最高研发状态	国家/地区	公司	日期
心绞痛	药物发现	美国	Allos Therapeutics, Inc.	-
肿瘤	药物发现	美国	Allos Therapeutics, Inc.	-
脑卒中	药物发现	美国	Allos Therapeutics, Inc.	-
创伤和损伤	药物发现	美国	Allos Therapeutics, Inc.	-