Liposomal 1,25 (OH)2 vitamin D3 compounds block proliferation and induce differentiation in myelomonocytic leukaemia cells

The vitamin D₃ derived hormone 1,25 (OH)₂ vitamin D₃ (1,25 D₃) is able to induce growth arrest and differentiation in myelomonocytic leukaemia cells. In order to allow for specific delivery to leukaemic cells the lipophilic compound was incorporated into the lipid membranes of liposomes. Liposomal 1,25 D₃ reduced proliferation as measured by ³H-thymidine incorporation in HL60 leukaemia cells by up to 60%. When liposomes were prepared at different concentrations of 1,25 D₃ 65% inhibition was achieved at 48 n M . The MC 1288 stereoisomer of 1,25 D₃ was more potent and had the same activity at 48 n M .
The effect of the liposomal compounds was specific to myeloid cells as they reduced proliferation in myelomonocytic HL60, monoblastic U937 and monocytic Mono Mac 6 cells but not in the T-cell lines Jurkat and Molt 4.
The antiproliferative effect of liposomal 1,25 D₃ was associated with an induction of differentiation since treated HL60 cells showed a monocytic morphology, increased expression of CD14 and decreased expression of CD33.
When peripheral blood leukaemic cells from M4 and M5 acute myeloid leukaemia (AML) patients were admixed with liposomal compounds an antiproliferative effect was seen in all five cases, including the two cases where free compounds led to enhanced growth. Liposomal delivery of 1,25 (OH)₂ vitamin D₃ may offer a novel approach to treatment of myelomonocytic leukaemia.     

Use of Mono Cortical Screws as an Aid to Zygomatic Complex Fracture Reduction

Introduction

Zygomatic complex fractures by virtue of its anatomic area poses a great challenge in reduction of the fracture. Uses of various methods have been mentioned in English literature.

Method

A new technique describing the use of reduction screw with a self-holding screwdriver in reduction of the zygomatic complex fracture.

Conclusion

We found the method to be simple and effective and recommend its application in daily practice.     

Postprandial coagulation activation in overweight individuals after weight loss: Acute and long-term effects of a high-monounsaturated fat diet and a low-fat diet

Diet is important in the prevention of cardiovascular disease, and it has been suggested that a high-MUFA diet is more cardioprotective than a low-fat diet. We hypothesised that the postprandial thrombotic risk profile is improved most favourably by a high-MUFA diet compared with a low-fat diet. This was tested in a parallel intervention trial on overweight individuals (aged 28.4 (SD 4.7) years) randomly assigned to a MUFA-diet (35-45% of energy as fat; > 20% as MUFA, n = 21) or a low-fat (LF) diet (20-30% of energy as fat, n = 22) for 6 months after a weight loss of ~ 10%. All foods were provided free of charge from a purpose-built supermarket. Meal tests designed after the same principles were performed before and after the dietary intervention, and blood samples were collected at 8.00 h (fasting), 12.00 h, and 18.00 h and analysed for factor VII coagulant activity (FVII:C), activated FVII, fibrinogen, prothrombin fragment 1 + 2 (F1 + 2), D-dimer, plasminogen activator inhibitor (PAI:Ag), and thrombin activatable fibrinolysis inhibitor. There were significant postprandial increases in F1 + 2 and D-dimer before and after dietary intervention, with significantly lower values after 6 months. No significant differences were observed between the postprandial changes induced by the two diets. The postprandial decrease in FVII:C and PAI:Ag did not differ before and after intervention, irrespective of the diets. Our findings suggest postprandial coagulation activation in overweight subjects with more pronounced acute than long-term effects. We observed similar effects of the MUFA diet and the LF diet on the postprandial prothrombotic risk profile.     

紫外分光光度法测定更昔洛韦滴眼液的含量

目的:建立更昔洛韦滴眼液含量的测定方法。方法:采用紫外分光光度法测定更昔洛韦的含量。结果:更昔洛韦在4~16μg/ml浓度范围内与吸收度有良好的线性关系,回归方程为A=0.0531 7C 0.010 4,r=0.999 9;平均回收率为99.83%,RSD为0.45%(n=5)。结论:该方法简便、快速、准确,适用于医院制剂的快速分析。     

Suppression of receptor-mediated Ca2+ mobilization and functional leukocyte responses by hyperforin

We have recently identified hyperforin, a lipophilic constituent of the herb Hypericum perforatum (St. John's wort), as a dual inhibitor of the proinflammatory enzymes cyclooxygenase-1 and 5-lipoxygenase. The aim of the present study was to further elucidate antiinflammatory properties and respective targets of hyperforin. We found that hyperforin inhibited the generation of reactive oxygen species (ROS) as well as the release of leukocyte elastase (degranulation) in human isolated polymorphonuclear leukocytes (PMNL), challenged by the G protein-coupled receptor (GPCR) ligand N-formyl-methionyl-leucyl-phenylalanine (fMLP) with an IC 50 approximately equal 0.3 microM. When PMNL were stimulated with phorbol-12-myristate-13-acetate (PMA) or ionomycin, hyperforin (up to 10 microM) failed to inhibit ROS production and elastase release, respectively. Moreover, hyperforin blocked receptor-mediated Ca(2+) mobilization ( IC 50 approximately equal 0.4 and 4 microM, respectively) in PMNL and monocytic cells, and caused a rapid decline of the intracellular Ca(2+) concentration in resting cells. In contrast, the Ca(2+) influx induced by ionomycin or thapsigargin was not suppressed. Comparative studies with the specific phospholipase C inhibitor U-73122 and hyperforin revealed similarities between both compounds. Thus, U-73122 and hyperforin blocked fMLP- and PAF-induced Ca(2+) mobilization, ROS formation, and elastase release, but failed to suppress these responses when cells were stimulated by PMA or ionomycin. Also, both compounds rapidly decreased basal Ca(2+) levels in resting cells and led to a rapid decline of the Ca(2+) elevations evoked by fMLP or PAF. Our data suggest that hyperforin targets component(s) within G protein signaling cascades that regulate Ca(2+) homeostasis, coupled to proinflammatory leukocyte functions.     

Enzymatically modified low-density lipoprotein upregulates CD36 in low-differentiated monocytic cells in a peroxisome proliferator-activated receptor-gamma-dependent way

Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been suggested to upregulate CD36. Since free oxidized polyunsaturated fatty acids are PPARgamma ligands, we studied the effects of LDL modified by the simultaneous action of sPLA2 and 15-lipoxygenase (15LO) on CD36 expression and PPARgamma activation in monocytic cells. Exposure of MM6 cells, which do not express CD36 or other scavenger receptors, to such enzymatically modified LDL (enzLDL) resulted in upregulation of CD36 surface protein and mRNA expression. Similar effects were observed with free 13-hydroperoxyoctadecadienoic acid but not its esterified counterpart. Less pronounced effects were observed with LDL modified by 15LO alone. Upregulation of CD36 was inversely correlated to the state of cell differentiation, as showed by lower response to enzLDL of the scavenger receptor-expressing MM6-sr and THP1 cells. Importantly, LDL modified by sPLA2 and 15LO did not efficiently induce upregulation CD36 in PPARgamma-deficient macrophage-differentiated embryonic stem cells confirming a role of PPARgamma in CD36 expression in cells stimulated with enzLDL. Our data show that LDL modified with physiologically relevant enzymes stimulates CD36 expression in non-differentiated monocytes and that this process involves PPARgamma activation. These effects of enzLDL can be considered pro-atherogenic in the context of early atherosclerosis.     

紫外分光光度法测定硫酸阿托品滴眼剂的含量

采用紫外分光光度法测定硫酸阿托品滴眼剂的含量,测定波长为２５６ｎｍ,在０．２￣１．２ｍｇ／ｍｌ浓度范围内吸光度与浓度符合Ｂｅｅｒ’ｓ定律,线性关系良好。     

Absence of central effects with levocabastine eye drops

Twelve healthy volunteers were randomly allocated to receiving in a double-blind cross-over fashion levocabastine eye drops (0.5 mg/ml solution) and placebo. They were advised to instill 2 drops per eye, four times daily. Each treatment was administered for a period of 1 week. Before and after each treatment period psychomotor function was assessed using Critical Flicker Fusion Test and the Choice Reaction Time Test. At the same time intervals a subjective evaluation of sedation was given using a Visual Analogue of Sedation. Both objective and subjective measurements showed that no significant treatment effects could be detected. It is concluded that repeated instillations of levocabastine eye drops are devoid of any sedative side effects.     

氧氟沙星滴眼液和滴耳液的研制

本文通过溶解度、稳定性、抑菌性实验，经过筛选，确定了氧氟沙星滴眼液和滴耳液的处方、制备方法和质控标准，并采用初均速法考察了两种制剂的稳定性。滴眼液和滴耳液的室温有效期分别为４．８１年和６．５５年。