Pharmacokinetics, metabolism and renal excretion of sulfatroxazole and its 5-hydroxy- and N4-acetyl-metabolites in man

Hydroxylation is the predominant pathway of metabolism for sulfatroxazole in the body, accounting for 70 per cent of the dose. Fifteen per cent of the dose is acetylated unimodally and 10 per cent is excreted unchanged. The half-lives of sulfatroxazole and its metabolites 5-hydroxysulfatroxazole and N4-acetylsulfatroxazole are approximately 22 h after administration of sulfatroxazole. N4-acetylsulfatroxazole, taken as parent drug, is eliminated by renal excretion (92 per cent of the dose). The initial elimination half-life of N4-acetylsulfatroxazole is 4.5 h, which later increases to 70 h as the result of the acetylation-deacetylation equilibrium. Probenecid inhibits the renal excretion of the metabolites 5-hydroxy- and N4-acetylsulfatroxazole. Inhibition of the N4-acetyl metabolite favours the deacetylation, which results in an increase of the T 1/2 of sulfatroxazole from 20 to 30 h. The protein binding value of sulfatroxazole is 84 per cent, that of N4-acetylsulfatroxazole is 37 per cent. Sulfatroxazole is excreted renally by passive processes, while the metabolites are excreted by both passive and active processes.     

包含颈外静脉的颈阔肌肌皮瓣修复口腔癌切除后缺损

目的探讨将颈外静脉包含在颈阔肌肌皮瓣内修复口腔癌切除后缺损的手术方法。方法先形成蒂在颌缘下包含颈外静脉的颈阔肌肌皮瓣，待口腔肿瘤切除后，将肌皮瓣经口底隧道引入口腔修复缺损。结果临床应用17例，肌皮瓣均无血运障碍，100％存活，其中有2例发生口面痿，经换药后痿口完全闭合。结论将颈外静脉包含在颈阔肌肌皮瓣内有助于肌皮瓣血循环的改善和存活率的提高。     

恶性淋巴瘤自体造血干细胞移植后复发的研究进展

自体造血干细胞移植 (ASCT)是治疗复发性、难治性和侵袭性恶性淋巴瘤的有效方法 ,但因存在体内肿瘤细胞负荷过多和移植物被肿瘤细胞污染 ,使移植后的复发率增高。为了提高ASCT的疗效 ,可采取 :①移植前美罗华体内净化 ,除去外周血B细胞 ,清除移植物的肿瘤细胞污染 ;②移植后用美罗华和非交叉耐药药物交替联合化疗 ,以杀伤体内肿瘤细胞 ;③移植前或后累及野放射治疗 (IFRT)辅助 ,降低原发灶的复发率     

莱菔硫烷对ox-LDL诱导血小板活化的抑制作用

目的：探讨莱菔硫烷（sulforaphane,SFN）对氧化低密度脂蛋白（oxidized low-density lipoprotein,ox-LDL）诱导血小板活化的影响及其可能的分子机制。方法：在体外实验中,将健康人纯化血小板与不同浓度的SFN(1.0、2.5、5.0μmol/L)共同孵育40 min,然后用ox-LDL激活血小板20 min,并检测血小板活化的指标,包括CD62P的表达、胞内血小板因子4(platelet factor4,PF4)和趋化因子配体5(chemokine ligand 5,CCL5)的释放水平。机制上,用Western blot蛋白免疫印迹法检测血小板肉瘤酪氨酸激酶（sarcoma tyrosine kinase,Src）及其下游的脾酪氨酸激酶（spleen tyrosine kinase,Syk）磷酸化水平;用活性氧（reactive oxygen species,ROS）检测试剂盒测定胞内总ROS水平。结果：ox-LDL诱导的血小板CD62P的表达以及PF4和CCL5的释放水平均可被SFN显著抑制（P <0.05）;SFN显著下调ox-LD...     

Effect of Gardenia extract ZG on the adsorption quantity of herpes simplex virus type 1 （HSV-1）

To observe the effect of Gardenia extract ZG on the adsorption quantity of herpes simplex virus type 1 (HSV-1) so as to explore the mechanism of its antiviral activity, fluorescein isothiocyanate (FITC) was used as the fluorescent probe to label viruses and heparin sodium was used as control. Meanwhile , the effect of Gardenia extract ZG on the adsorption quantity on the surface of Hep-2 cells was determined by flow cytometry. It was demonstrated that adsorption of HSV-1 on the surface of Hep-2 cells exhibited the character of saturation and specificity and heparin sodium could prevent attachment of viruses on these cells. These results are in accord with those reported previously. It was also proved that the manner of drug-use prior to adsorption or simultaneous use of drug and adsorption was better than adsorption prior to drug-use, and the inhibition rates of the former and latter manner were 84. 76% and 82.92% respectively. Three manners of drug-use with Gardenia extract ZG were all effective to reduce the adsorption quantity of viruses, especially the manner of simultaneous use of drug and adsorption with an adsorption inhibition rate of 68.46% . From the above observation, it is apparent that the mechanism of anti-viral activity of Gardenia extract ZG may be via several steps involved in the HSV-1 adsorption.     

High-performance liquid chromatography of HIV protease inhibitors in human biological matrices

Methods for HPLC analysis of protease inhibitors (PIs) in human biological matrices were reviewed. Assays have been developed for analysis of single PIs or for simultaneous measurement of multiple PIs in plasma-serum, saliva, cerebrospinal fluid and semen. Liquid-liquid extraction was most often applied for sample pretreatment, but solid-phase extraction and protein precipitation were used as well. Reversed-phase or ion-pair chromatography have been used to separate PIs. Detection of PIs should be sensitive enough for quantitation of plasma concentrations below trough levels of single PIs, or below proposed therapeutic thresholds for PIs. The large majority of assays employs UV detection. As the potential for interferences is large, the selectivity of every method should be evaluated properly. The available high-performance liquid chromatography (HPLC) methods have been applied in clinical pharmacokinetic studies and for therapeutic drug monitoring of PIs. Participation in an interlaboratory quality control program is recommended for every laboratory engaged in the bioanalysis of PIs.     

耳大神经及腮腺筋膜解剖的再认识与腮腺切除手术的改良

目的：对耳大神经及腮腺筋膜解剖进行再认识，由此改良腮腺切除手术方法。方法：解剖成人尸体10侧，术中活体解剖20侧，对耳大神经和腮腺筋膜的解剖要素进行观察。根据观察结果进行改良腮腺切除术14例，即在腮腺筋膜表面翻瓣后，由前向后另翻腮腺筋膜瓣，切除腮腺后将筋膜瓣复位缝合，完整保留耳大神经和腮腺筋膜。结果：耳大神经在下颌角水平之上0-2cm依次分耳后、耳垂、耳前支，神经主干末段和分支起始段均分布于腮腺筋膜浅层表面，后者致密，其致密纤维包裹在神经周围。改良手术后2例（14．3％）发生轻度Frey’s综合征，无1例发生术区皮肤长期麻木、长期面瘫、涎瘘及肿瘤复发。结论：耳大神经各分支和腮腺筋膜具有不可代替的解剖生理功能，改良术式能将两者完好保留，显著降低术后并发症。     

Pharmacokinetics of cefradine, sulfamethoxazole and trimethoprim and their metabolites in a patient with peritonitis undergoing continuous ambulatory peritoneal dialysis

Cefradine and co-trimoxazole pharmacokinetics were studied in a patient with peritonitis that complicated continuous ambulatory peritoneal dialysis (CAPD). Concentrations in the plasma reached after oral administration of 500 mg cefradine four times daily and 400/80 mg co-trimoxazole four times daily were for cefradine 100g/ml, for trimethoprim 15g/ml, and for sulfamethoxazole 100/ml, respectively. In the dialysate concentrations were reached of 35–70/ml cefradine, 2–5/ml trimethoprim and 8–17g/ml sulfamethoxazole. The values for sulfamethoxazole are regarded too low to be clinically effective. Half-lives protein binding values and CAPD clearances are presented. Low CAPD clearances were obtained during the night and high values during the day. The dosage yielded too high plasma trimethoprim concentrations, while sulfamethoxazole dialysate concentrations were too low. It seems questionable therefore whether co-trimoxazole can be used orally for the treatment of CAPD peritonitis.