用噬菌体筛选抗癌药

有些有诱导及（或）抗噬菌体的物质可能是抗癌药。我们用噬菌体对２８７种中草药进行了抗癌药初筛。结果显示：①１４种中草药有诱导及抗噬菌体作用；②１５种中草药仅有诱导作用；③２８种中草药有强抗噬菌体作用。若进一步用肿瘤细胞培养或实验肿瘤动物进行筛选研究，这些中草药可作为首选药。     

感染和炎症显像剂的研究与应用

综述了目前主要炎症显像剂的研究与临床应用情况,主要包括标记的小分子化合物、白细胞、大分子蛋白、脂质体、抗生素和生物素等。     

Clinical pharmacological study of a plasma‐derived factor VIIa and factor X mixture (MC710) in haemophilia patients with inhibitors – Phase I trial

Summary. MC710, a combined product of plasma‐derived activated factor VII (FVIIa) and factor X (FX) at a protein weight ratio of 1:10, is a novel bypassing agent for haemostasis in haemophilia patients with inhibitors. In this study, pharmacokinetic (PK), pharmacodynamic (PD) parameters and safety of single doses of MC710 were investigated in 11 male haemophilia patients with inhibitors in a non‐bleeding state. This was a multi‐centre, open‐labelled, non‐randomized, active controlled crossover, dose‐escalation study of five doses (20–120 μg kg⁻¹ of FVIIa) with re‐administration of different MC710 dosages to the same subjects. The active controls were NovoSeven (120 μg kg⁻¹) and/or FEIBA (50 and 75 U kg⁻¹) which were used to compare PD parameters. The area under the curve (AUC) and maximum plasma concentration (C_max) of MC710 active ingredients increased dose‐dependently within the range of 20 and 120 μg kg⁻¹. After administration of MC710, activated partial thromboplastin time (APTT) was dose‐dependently improved and prothrombin time (PT) was shortened to approximately 6 s at 10 min, and APTT improvement and PT shortening effects were maintained until 12 h after administration of MC710 at all doses. No serious or severe adverse event was observed after administration of MC710; furthermore, several diagnostic marker values and those changes did not indicate any signs of disseminated intravascular coagulation (DIC). These results suggest that MC710 would have haemostatic potential equal to or greater than NovoSeven and FEIBA and was be tolerable when given at doses up to 120 μg kg⁻¹.     

A Systematic Review of Statin Efficacy in Asthma

Background. Statins are known for their lipid-lowering effects and role in the treatment of atherosclerotic disease. They also have anti-inflammatory and immunomodulatory properties which could benefit asthma patients. We aimed to review the evidence on the efficacy and safety of statins in asthma-related outcomes. Methods. A systematic review of the literature on the effects of statins on asthma-related outcomes was performed following a search of the National Guideline Clearinghouse, Cochrane, Scopus, and Pubmed Medline databases in January 2012. Randomized controlled trials (RCTs) and observational studies (cohort/case–control design) assessing the effect of statins were included. The Grading of Recommendations Assessment Development and Evaluation (GRADE) system was used to rate the levels of evidence and grade of recommendation. Results. Twenty-four of the 379 articles retrieved electronically and one article identified by hand search were selected for full-text scrutiny by two independent reviewers. Eight studies were included: six RCTs and two observational studies. Statin use was not associated with consistent, statistical significant improvements in patient outcomes (asthma control, quality of life, steroid-sparing effects) or disease outcomes (lung function, airway responsiveness), and all the studies analyzed had low or very low quality of evidence. Inflammatory outcome improvements were observed in mild allergic asthma. Conclusion. Statins do not seem to have any additional benefit in asthma control or steroid-sparing effect in asthma treatment. Considering the prevalence of both statin use and asthma, more, better designed studies are needed to determine whether a specific phenotype of asthma exists that could benefit from statin treatment.     

High Blood Pressure Induced by Audiovisual Stimulation in Young Rats: Effect of Antihypertensive Agents

ABSTRACT

High systolic blood pressure (BP) was induced in young Wistar rats by daily exposure for 30 mins to environmental stimuli consisting of intense (100 dB) sound of 7500 cps and flashing light (0.3 cps). Maximal BP enhancement was obtained after the application of both these stimuli for 3 consecutive days. Such a hypertensive response was detected 24 hrs, but not 1 hr after the trial. High BP backed to normal 72 hrs after discontinuation of the audiovisual stimulation trials. Clinically effective antihypertensive agents (clonidine, prazosin, propranolol, practolol and metoprolol) as well as a new compound under investigation (cicletanine) were proved active in this model. Normotensive nonstressed rats run in parallel did not show any variation in their BP after administration of the same dose of the drugs assayed. This experimental model of hypertension may be a useful tool not only to test new antihypertensive agents but also to study the intriguing question of the role of stress in the development and maintenance of essential hypertension.     

Development of anti-neutrophil cytoplasmic antibody-associated vasculitis in a patient with Graves’ disease independent of anti-thyroid drug therapy

Abstract

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in patients with Graves’ disease (GD) is linked with the use of anti-thyroid drugs (ATDs). We report the co-occurrence of AAV and GD in a patient that was independent of ATD therapy. A 38-year-old white male presented with systemic symptoms, palpitations, tremors, purpuric skin lesions, and digital pain. Physical examination and biological tests confirmed GD. He quickly developed multiple digital gangrenes and testicular pain/mass. Skin and testicular biopsies showed granulomatous vasculitis of the small- and medium-sized vessels, while his serum contained anti-proteinase-3 antibody.     

降压药物在妊娠期高血压疾病中应用的争议与发展

妊娠期高血压疾病(hypertensive disorders of pregnancy,HDP)是产科最重要合并症之一,严重影响母婴健康。然而,何时采用降压治疗、如何正确应用降压药物在HDP的治疗中始终存在争议,并在争议中不断发展。循证医学显示,肼苯哒嗪和硝苯地平已不再是HDP降压治疗的一线药物,而拉贝洛尔、尼卡地平也许是更好的选择。     

Preclinical Safety and Pharmacology of Hematide™, a Peptidic Erythropoiesis Stimulating Agent (ESA), in Rats and Monkeys

The pharmacology, toxicokinetics, and safety of Hematide^TM, a synthetic peptidic erythropoiesis-stimulating agent (ESA), were characterized. Hematide was given intravenously (0, 0.5, 5, and 50 mg/kg) weekly for five weeks with a 6- (rat) and 12-week (monkey) recovery period. The pharmacological action of Hematide resulted in polycythemia. Histopathology consistent with drug-induced exaggerated pharmacology was observed primarily in rats. Secondary sequelae resulting from pronounced polycythemia was considered the cause of deaths in rats and a single high-dose monkey. Toxicokinetic analysis indicated prolonged exposure. In conclusion, Hematide is a potent ESA and the safety and efficacy profile support clinical development.     

Genotoxic assessment and toxicity evaluation of peginesatide in CByB6F1 hybrid mice

Peginesatide is a PEGylated, investigational, peptide-based erythropoiesis-stimulating agent (ESA) that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. Clinical use of peginesatide is anticipated to result in chronic dosing in chronic kidney disease (CKD) patients, and the nonclinical data to support development should include an evaluation of carcinogenic potential evaluation. Peginesatide was not mutagenic or clastogenic in a standard genotoxicity battery of tests. Doses for a rasH2 transgenic mouse carcinogenicity assay were defined in a 28-day study in the wild-type littermates of the rasH2 transgenic mouse strain, using intravenous doses of 1–25?mg/kg on days 1 and 22. The findings were consistent with exaggerated pharmacology, including polycythemia, with associated increases in hemoglobin level and extramedullary hematopoiesis and bone marrow hypercellularity.     

Patient Blood Management: Use of Topical Hemostatic and Sealant Agents

Patient blood management is the scientific use of safe, effective medical and surgical techniques designed to conserve blood, prevent anemia, decrease bleeding, and optimize coagulation in an effort to improve patient outcomes. Perioperative and primary care nurses play a vital role in promoting and making the best use of patient blood management and can play a key role in implementing effective strategies that decrease or eliminate patient exposure to allogeneic blood. The fast and effective minimization of intraoperative bleeding is integral in an effective blood management program. Topical hemostatic and sealant agents can be used to improve blood conservation, reduce overall procedure time, and contribute to faster patient recovery based on specific clinical situations. The proper selection of hemostatic agents can greatly influence the patient’s clinical outcomes.