目的:研究醋甲唑胺(methazolamide，MTZ)治疗正常压力脑积水(NPH)患者的有效性及安全性。方法:本研究为随机、双盲、安慰剂对照前瞻性临床研究。收集我院2019年9月至2021年3月35例NPH患者，其中包括29例特发性正常压力脑积水(iNPH)和6例继发性正常压力脑积水(sNPH)患者，上述患者因各种原因不适宜或拒绝手术治疗。随机分为药物组和安慰剂组，给予口服MTZ或安慰剂25 mg，2次/d，1周后无不适增加至50 mg，2次/d治疗。口服前、口服1月后分别进行10 m步态评分、认知功能评分、特发性正常压力脑积水分级量表(iNPHGS)评分、头MRI检查，口服3个月后进行iNPHGS评分。主要疗效终点为用药后3个月iNPHGS评分，次要疗效终点为用药后1个月上述各项评分。结果:35例NPH患者中28例进入最终分析。药物组18例，安慰剂组10例。用药1月后药物组MOCA评分[(16.2±8.8)分和(14.8±8.7)分， t＝-2.68， P＝0.02]、10 m步态评分[(22.3±11.2)分和(25.6±12.9)分， t＝2.76， P＝0.02]、iNPHGS评分[(7.3±3.2)分和(8.1±3.5)分， t＝4.08， P<0.01]均较基线改善；用药3个月后药物组iNPHGS评分(6.1±2.4)分较基线时( t＝5.07， P<0.01)和1个月时改善( t＝4.11， P<0.01)；而对照组用药1个月和3个月后各项评分较基线均无明显改善(均 P>0.05)；用药1个月后药物组较对照组10 m步态评分、iNPHGS评分改善(均 P<0.05)；用药3个月后iNPHGS评分相对于基线水平较对照组改善( t＝-4.41， P<0.05)。上述35例患者未出现低钾、酸中毒等严重不良反应。两组间不良事件差异无统计学意义( χ2＝0.01， P＝1.00)。 结论:醋甲唑胺可有效改善部分不能手术的NPH患者临床症状，且安全性良好，

目的 研究醋甲唑胺(Methazolamide,MTZ)的抗缺氧效应及其在预防急性高原反应中的作用.方法 小鼠灌胃给予MTZ后,通过密闭缺氧实验、心肌缺氧实验、大脑缺血缺氧实验、亚硝酸钠中毒实验,分别检测小鼠密闭缺氧状态下的标准耐受时间、小鼠心肌缺氧标准耐受时间、断头处死后张口动作持续时间、亚硝酸钠中毒后存活时间等指标.在高原现场比较志愿者口服MTZ或安慰剂后,急性高原病的发病率、血氧饱和度及心率.结果 MTZ 400、200、100 mg/kg组的小鼠密闭缺氧状态下的标准耐受时间均显著高于对照组[25.01 (2.40)、21.11 (4.64)、16.39(5.14)vs14.62(3.62) min/100 mL,P＜0.05].同时,200 mg/kg的MTZ还可以显著延长小鼠心肌缺氧标准耐受时间[(13.08±1.35)min/100 mLvs(8.30±0.94) min/100 mL,P＜0.01]和断头处死后张口动作持续时间(43.22±8.23)s vs(20.44±2.60)s,P＜0.01].人群试验表明MTZ显著降低急性高原病的发病率(19.4％ vs 3.45％,P＜0.05),并显著提高急进高原人群的血氧饱和度[85％(4％)vs87％(3.5％),P ＜0.05],降低心率[100(17)/minvs90(21.5)/min,P＜0.05].结论 MTZ可显著提高机体抗缺氧能力,能有效预防急性高原病.

目的 观察曲伏前列素滴眼液治疗挫伤后继发性青光眼的临床效果.方法 收集2012年1月至2015年1月眼球挫伤后继发性青光眼65例(65眼),随机分为试验组和对照组.对照组32例应用噻吗心安及阿法根滴眼液滴眼及尼目克司口服.试验组33例应用曲伏前列素滴眼滴眼.随访观察3个月,观察指标主要为眼压及不良反应.结果 试验组眼压从(42.51±7.93)mmHg降至(20.54±6.55) mmHg(1 mmHg =0.133 kPa),降眼压有效率为90.9％.对照组眼压从(44.84±8.17) mmHg降至(32.43±10.72) mmHg,有效率为46.8％.二组有效率相比差异有统计学意义(x2=14.788,P=0.000).完全控制率试验组为75.76％,对照组为18.75％.二组相比差异有统计学意义(x2=21.164,P=0.000).治疗有效的45眼随访3个月,最终眼压低于21 mmHg者试验组28眼,治愈率84.84％,对照组13眼,治愈率40.62％.两组最终治愈率差异有统计学意义(x2=13.642,P =0.000).未发现挫伤性轻度眼内炎症反应加重或其他严重不良反应.结论 应用曲伏前列素治疗眼挫伤后继发性青光眼效果良好.

目的 分析醋甲唑胺诱发的Stevens-Johnson综合征和中毒性表皮坏死松解症.方法 回顾性分析44例由醋甲唑胺诱导的Stevens-Johnson综合征和中毒性表皮坏死松解症的临床资料.对年龄、性别、种族、潜伏时间、临床表现和HLA基因型等进行分析.结果 患者年龄平均(47.63±15.43)岁.醋甲唑胺用量为(90.85±45.51)mg/d.潜伏时间(13.72±8.39)d.初起时皮肤和黏膜皮疹,继而进展至四肢、躯干、面部等,出现皮肤黏膜与其下组织脱离.高峰期结束后,水泡结痂干燥,裂开脱落.26例进行了HLA基因检测,HLA-B59阳性率为88.46％.糖皮质激素的应用是主要治疗手段.结论 醋甲唑胺诱导的Stevens-Johnson综合征和中毒性表皮坏死松解症病情严重,出现可疑症状和体征时应及时停用醋甲唑胺,应用糖皮质激素治疗有望控制病情.

The present study aimed to develop and optimize chitosan coated solid lipid nanoparticles (chitosan-SLNs) encapsulated with methazolamide.Chitosan-SLNs were successfully prepared by a modified oil-in-water emulsification-solvent evaporation method with glyceryl monostearate as the solid lipid and phospholipid as the surfactant.Systematic screening of formulation factors was carried out.The optimized formula for preparation was screened by orthogonal design as well as Box-Behnken design with entrapment efficiency,particle size and zeta potential as the indexes.The entrapment efficiency of the optimized formulation (methazolamide-chitosan-SLNs) prepared was (58.5 ± 4.5)％,particle size (247.7 ± 17.3) nm and zeta potential (33.5 ± 3.9) mV.Transmission electron microscopy showed homogeneous spherical particles in the nanometer range.A prolonged methazolamide in vitro release profile was obtained in the optimized chitosan-SLNs suspension compared with methazolamide solution.No ocular damages were observed in the susceptibility test on albino rabbits.The results suggest that the combination of orthogonal design and Box-Behnken design is efficient and reliable in the optimization of nanocarriers,and chitosan-SLNs is a potential cartier for ophthalmic administration.

Acetazolamide (molecular mass (MM), 222) belongs to the class of sulfonamides (R-SO2-NH2) and is one of the strongest pharmacological inhibitors of carbonic anhydrase activity. Acetazolamide is excreted unchanged in the urine. Here, we report on the development, validation and biomedical application of a stable-isotope dilution GC-MS method for the reliable quantitative determination of acetazolamide in human urine. The method is based on evaporation to dryness of 50 μL urine aliquots, base-catalyzed derivatization of acetazolamide (d0-AZM) and its internal standard [acetylo-2H3]acetazolamide (d3-AZM) in 30 vol％ pentafluorobenzyl (PFB) bromide in acetonitrile (60 min, 30 °C), reconstitution in toluene (200μL) and injection of 1-μL aliquots. The negative-ion chemical ionization (NICI) mass spectra (methane) of the PFB derivatives contained several intense ions including [M]- at m/z 581 for d0-AZM and m/z 584 for d3-AZM, suggesting derivatization of their sulfonamide groups to form N,N-dipenta-fluorobenzyl derivatives (R-SO2-N(PFB)2), i.e., d0-AZM-(PFB)2 and d3-AZM-(PFB)2, respectively. Quanti-fication was performed by selected-ion monitoring of m/z 581 and 83 for d0-AZM-(PFB)2 and m/z 584 and 86 for d3-AZM-(PFB)2. The limits of detection and quantitation of the method were determined to be 300 fmol (67 pg) and 1μM of acetazolamide, respectively. Intra-and inter-assay precision and accuracy for acetazolamide in human urine samples in pharmacologically relevant concentration ranges were determined to be 0.3％-4.2％and 95.3％-109％, respectively. The method was applied to measure urinary acetazolamide excretion after ingestion of a 250 mg acetazolamide-containing tablet (Acemit?) by a healthy volunteer. Among other tested sulfonamide drugs, methazolamide (MM, 236) was also found to form a N,N-dipentafluorobenzyl derivative, whereas dorzolamide (MM, 324) was hardly detectable. No GC-MS peaks were obtained from the PFB bromide derivatization of hydrochlorothiazide (MM, 298), xipamide (MM, 355), indapamide and metholazone (MM, 366 each) or brinzolamide (MM, 384). We demonstrate for the first time that sulfonamide drugs can be derivatized with PFB bromide and quan-titated by GC-MS. Sulfonamides with MM larger than 236 are likely to be derivatized by PFB bromide but to lack thermal stability.