银黄吸入溶液的指纹图谱建立及酚酸类成分的含量测定

目的 建立银黄吸入溶液的指纹图谱,并同时测定新绿原酸、绿原酸、隐绿原酸的含量.方法 以黄芩苷为参照峰,采用高效液相色谱(HPLC)法建立银黄吸入溶液的指纹图谱;以绿原酸为参照物,采用斜率校正法计算新绿原酸、隐绿原酸的相对校正因子,再根据相对校正因子计算两者的含量,并将上述一测多评(QAMS)法的检测结果与外标法进行比较...     

Sex variation in ascorbic acid catabolism.

Male and female albino rats of same age and body weight were pair fed with laboratory stock diet and ascorbic acid, dehydroascorbic acid and diketogulonic acid were determined in the liver and urine, while in blood only ascorbic acid was estimated. Male rats had concentration higher of ascorbic acid in liver and urine as compared with females, while there were no significant variations in the contents of dehydroascorbic acid and diketogulonic acid. Hepatic and renal 2, 3-diketoaldonate decarboxylase, and hepatic dehydroascorbatase were also found to be significantly higher in male rats. Similar sex variations were also observed in ascorbic acid catabolism in guinea pigs without any differences in urinary ascorbic acid contents.     

亚砷酸联合全反式维甲酸治疗急性早幼粒细胞白血病的临床分析

目的探讨亚砷酸联合全反式维甲酸治疗急性早幼粒细胞白血病的临床效果。方法将本院2008年1月～2013年9月收治的64例急性早幼粒细胞白血病患者随机分为4组,每组各16例。联合组给予亚砷酸和全反式维甲酸进行双诱导治疗,亚砷酸组给予亚砷酸治疗,维甲酸组给予全反式维甲酸治疗,化疗组给予常规化疗治疗。结果联合组、亚砷酸组的所有患者（100％）完全缓解,无死亡病例,维甲酸组13例（81．2％）患者达到完全缓解,1例死亡,化疗组仅6例（37．5％）完全缓解,2例死亡,前3组的完全缓解率均显著高于化疗组（P〈0.05）;联合组患者用药至完全缓解的时间明显短于亚砷酸组、维甲酸组（P〈0.05）;联合组患者凝血指标恢复正常所用的时间短于亚砷酸组、维甲酸组（P〈0.05）;肝功能损伤情况：联合组最严重,亚砷酸组次之,维甲酸组较轻,化疗组最轻（P〈0.05）,化疗组的胃肠道反应、皮肤损伤情况较严重,受影响患者明显多于其他3组（P〈0.05）。结论亚砷酸联合维甲酸治疗急性早幼粒细胞白血病短期效果显著,完全缓解率高,并可缩短患者的完全缓解时间。     

花粉超临界提取物中棕榈酸和亚麻酸的含量测定及药效相关性评价

对10种花粉的超临界提取物经皂化后的棕榈酸和亚麻酸进行定量分析,并评价了棕榈酸和亚麻酸与抗前列腺增生活性的相关性。以十七烷酸为内标,以三氟化硼-甲醇为甲酯化试剂,皂化后样品中棕榈酸和亚麻酸经甲酯化后,用气相色谱法测定含量。棕榈酸和亚麻酸的线性范围分别为两者与十七烷酸的质量比mi/ms(十七烷酸)0.33～3.0和0.356～3.2,平均回收率分别为100.22%(RSD3.27%)和99.28%(RSD2.98%)。棕榈酸含量与药效有较好的相关性。     

海金沙提取物中香豆酸和咖啡酸的测定及稳定性研究

目的建立了海金沙提取物中香豆酸和咖啡酸的测定方法,并研究了二者在不同条件下的稳定性。方法选用E-clipse XDB-C18色谱柱,以甲醇-1%乙酸水溶液作为流动相进行梯度洗脱;考察了光照、放置时间等因素对咖啡酸和香豆酸稳定性的影响。结果香豆酸和咖啡酸得到很好的分离。以水为溶剂,咖啡酸和香豆酸在冷藏避光条件下储存比较稳定。结论为香豆酸和咖啡酸的提取、分析及其相关制剂的生产提供参考。     

Mesophase formation during cholesterol gallstone dissolution in human bile: effect of bile acid composition

Duodenal bile obtained from patients with gallstones who were acutely infused with chenodeoxycholic acid, ursodeoxycholic acid, or cholic acid were examined for the propensity toward the formation of a liquid crystalline mesomorphic phase when cholesterol gallstones were incubated in these bile acids. Bile taken from patients infused with ursodeoxycholic acid was found to be enriched in ursodeoxycholic acid; mesophase formation was detected in these samples but not in bile from patients infused with chenodeoxycholic acid or cholic acid.     

动态监测血乳酸对危重症患儿预后评价的意义

目的 探讨血乳酸水平与小儿危重病评分（PCIS）之间的相关性及血乳酸动态监测指标与患儿预后的关系.方法 比较乳酸升高组及乳酸正常组的住院情况;按PCIS评分分组,探讨血乳酸值与PCIS评分的相关性;根据预后将乳酸升高的危重患儿分为死亡组和存活组,比较两组患儿的乳酸指标和反映脏器/系统功能的临床指标的差异,利用Logistic回归分析的方法找出与预后显著相关的指标.结果 血乳酸升高组患儿的PCIS评分显著降低,休克发生率、MODS发生率及住院病死率明显上升,与乳酸正常组相比差异有统计学意义;随着PCIS评分降低,入ICU乳酸值、乳酸峰值明显增高,与PCIS评分有显著的线性相关关系（r分别为-0.455、-0.504,P＜0.01）;高乳酸血症患儿中,乳酸峰值、12 h乳酸清除率与患儿的预后明显相关.结论 血乳酸水平与PCIS评分存在明显线性相关关系,乳酸峰值、12 h乳酸清除率是评价患儿预后的良好指标.     

Is your patient taking the medicine? A simple assay to measure compliance with 5‐aminosalicylic acid‐containing compounds

BACKGROUND: Poor compliance with 5-aminosalicylic acid therapy has been reported amongst patients with inflammatory bowel disease. Currently, there is no easy method to monitor 5-aminosalicylic acid; however, the chemical similarity between 5-aminosalicylic acid and salicylate might provide a solution. AIM: To determine the feasibility of using salicylate levels to monitor compliance with 5-aminosalicylic acid medication. METHODS: Thirty-six patients with inflammatory bowel disease, taking maintenance 5-aminosalicylic acid, provided either a paired serum and urine sample or an intestinal biopsy. Samples were split into two: half were sent to the hospital biochemistry department for salicylate measurement, and half were analysed for 5-aminosalicylic acid and its metabolite, N-acetyl-5-aminosalicylic acid, using high performance liquid chromatography. Correlation between the results was calculated. RESULTS: Serum and urine were available for 25 patients. Serum salicylate was undetectable, but urinary salicylate ranged from 31 to 3254 microg/mL. The correlations between urinary salicylate and 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid were 0.96 (95% confidence interval, 0.91-0.98) and 0.9 (95% confidence interval, 0.77-0.96), respectively. Sixteen biopsies were available from 13 patients. The 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid concentrations were 0.2-657 ng/mg and 1.6-1598 ng/mg, respectively; there was no correlation with bowel salicylate. CONCLUSIONS: The close correlation between 5-aminosalicylic acid and salicylate levels offers a simple method to assess compliance with 5-aminosalicylic acid therapy.     

Double-blind comparison of 5-aminosalicylic acid and acetyl-5-aminosalicylic acid suppositories in patients with idiopathic proctitis

Suppositories containing 300 mg 5-aminosalicylic acid (1.96 mmol) or 425 mg acetyl-5-aminosalicylic acid (1.96 mmol) were used in 40 patients with idiopathic proctitis to determine the efficacy of acetyl-5-aminosalicylic acid in treating this bowel inflammation. Each patient was treated with 5-aminosalicylic acid or acetyl-5-aminosalicylic acid suppositories twice daily for 4 weeks in a double-blind trial. Four patients were included twice in the trial. The second time they were treated with the alternative regimen. Six patients in the acetyl-5-aminosalicylic acid group did not complete the trial, four of them because of diarrhoea. Complete clinical remission with normal rectal mucosa on sigmoidoscopy was achieved in 10 out of 18 patients on 5-aminosalicylic acid and in only two out of 15 in the acetyl-5-aminosalicylic acid group (P = 0.03). A favourable histological improvement was demonstrated with 5-aminosalicylic acid suppositories, but the difference with acetyl-5-aminosalicylic acid was not significant (P = 0.059). Three of the four patients who received both drugs recovered with 5-aminosalicylic acid; in none of them was acetyl-5-aminosalicylic acid effective. The results from this study and from previous investigations show that acetyl-5-aminosalicylic acid is not superior to placebo.     

Randall斑泌尿系结石患者的代谢评估

摘要：目的 通过对Randall斑结石患者进行24 h尿代谢分析,探讨Randall斑患者的结石危险因素及机制。方 法 收集 2017 年 10 月—2018 年 10 月于我院接受住院治疗的泌尿系结石患者 50 例,其中有 Randall 斑结石患者 （Randall斑组）30例,无Randall斑结石患者（无Randall斑组）20例,另择我院同期健康体检者30例为对照组。收集 患者24 h尿液进行尿液成分分析,对于排出的结石采用红外光谱分析仪检测结石成分。结果 Randall斑组中结石 的大小、位置、所在侧和结石成分与无Randall斑组差异均无统计学意义。与对照组相比,无Randall斑组24 h尿液中 枸橼酸含量降低,草酸、磷酸含量升高（P＜0.05）,Randall斑组24 h尿液中枸橼酸含量降低,草酸、磷酸、钠、钙含量升 高（P＜0.05）。与无 Randall 斑组相比,Randall 斑组 24 h 尿液中枸橼酸含量降低,草酸、磷酸、钠、钙含量升高（P＜ 0.05）。结论 Randall 斑患者 24 h 尿液中高钠、钙、草酸、磷酸和低枸橼酸对结石的发生发展有重要影响,应限制 Randall斑的泌尿系结石患者草酸、钠、钙、磷酸等的摄入并酌情补充枸橼酸。     

Use of hexadeuterated valproic acid and gas chromatography-mass spectrometry to determine the pharmacokinetics of valproic acid

Di-[( 3,3,3-2H3]propyl)acetic acid, a hexadeuterated analogue of valproic acid, was synthesized and its pharmacokinetic properties compared with valproic acid. Concentrations of valproic acid and [2H]valproic acid in serum and saliva were determined by GC-MS using selected-ion monitoring. Saliva drug levels were measured with good precision down to 0.1 microgram/mL. Kinetic equivalence of valproic acid and [2H]valproic acid was demonstrated in a single-dose study in a human volunteer. An isotope effect was observed for omega-oxidation, but the difference in metabolism was not sufficient to make [2H]valproic acid biologically nonequivalent. The application of [2H]valproic acid to determine the kinetics of valproic acid under steady-state concentrations was evaluated in the same volunteer. The kinetic data obtained with [2H]valproic acid was consistent with previously reported values for valproic acid including kinetic differences observed between single-dose and steady-state experiments. Saliva levels of valproic acid were found to give a good correlation (r = 0.953) with total serum valproic acid under multiple-dose conditions. A concentration dependence was found for the ratio of saliva valproic acid to free valproic acid in serum, low ratios being observed at high serum concentrations of valproic acid.     

Peptide sweeteners. 6. Structural studies on the C-terminal amino acid of L-aspartyl dipeptide sweeteners

Stereochemical and structural aspects of the variations in the C-terminal residue of L-aspartyl-L-phenylalanine methyl ester have been investigated. Novel configurational analogues such as L-aspartyl-D-alanine benzyl ester and L-aspartyl-D-alpha-aminobutyric acid benzyl ester were found to be sweet. In addition, chiral and achiral alpha, alpha-dialkylglycine and alpha-aminocycloalkanecarboxylic acids were incorporated into the dipeptides. The L-aspartic acid based dipeptide derivatives of alpha-aminoisobutyric acid methyl ester, alpha-aminocyclopropanecarboxylic acid methyl ester, alpha-aminocyclobutanecarboxylic acid methyl ester, and alpha-aminocyclopentanecarboxylic acid methyl ester are sweet. Dipeptides with alpha-aminocyclohexanecarboxylic acid methyl ester and alpha-aminocycloheptanecarboxylic acid methyl ester are bitter, whereas the analogues with alpha-aminocyclooctanecarboxylic acid methyl ester, alpha, alpha-diethylglycine methyl ester, and alpha-aminoisobutyric acid benzyl ester are tasteless. Aspects on chirality and effective volume of the C-terminal residue are discussed and correlated with taste.     

Pharmacokinetics of alpha-lipoic acid in subjects with severe kidney damage and end-stage renal disease

In an open-label, parallel-group study involving 16 patients (8 with severely reduced renal function, 8 with end-stage renal disease needing hemodialysis), the effect of renal function on the pharmacokinetics, metabolism, and safety and of alpha-lipoic acid (thioctic acid) was evaluated by comparing the pharmacokinetic parameters with those of a reference group of 8 healthy subjects. Alpha-lipoic acid 600 mg was administered orally once daily for 4 days, and the pharmacokinetic parameters were measured on days 1 and 4. The mean percentage of the administered dose excreted in urine as parent compound was 0.2 and 0.05 in healthy subjects and subjects with severely reduced renal function, respectively. Assuming a bioavailability of 30%, this represents 0.67% and 0.17% of the bioavailable amount of alpha-lipoic acid, respectively. The percentage of total urinary recovered amounts of alpha-lipoic acid and 5 of its metabolites was 12.0 on both days. The respective values for patients with severe kidney damage were 5.2% (day 1) and 6.4% (day 4). The total percentage of the administered dose removed by hemodialysis was 4.0 in patients with end-stage renal disease. Renal clearance of alpha-lipoic acid and its major metabolites, 6,8-bismethylthio-octanoic acid, 4,6-bismethylthio-hexanoic acid and 2,4-bismethylthio-butanoic acid, were significantly decreased in subjects with kidney damage compared to the reference group. Apparent total clearance of alpha-lipoic acid was poorly correlated with creatinine clearance. There is strong evidence that alpha-lipoic acid is mainly excreted by nonrenal mechanism or further degraded to smaller units in the catabolic process. The significantly increased area under the curve values of 4,6-bismethylthio-hexanoic acid and half-lives of 2,4-bismethylthio-butanoic acid on both days in patients with severely reduced function and end-stage renal disease were not considered to be clinically relevant. Although trough levels of both metabolites tend to increase slightly in these subjects, no accumulation effects were detected. We conclude that the pharmacokinetics of alpha-lipoic acid are not influenced by creatinine clearance and are unaffected in subjects with severely reduced kidney function or end-stage renal disease. Hemodialysis did not significantly contribute to the clearance of alpha-lipoic acid. Hence, dose adjustment of alpha-lipoic acid is not necessary in patients with renal dysfunction.     

Steady state pharmacokinetics of oral treatment with 13-cis-retinoic acid or all-trans-retinoic acid in male and female adult rats

Male and female Sprague-Dawley rats were orally gavaged with 13-cis-retinoic acid (7.5 or 15 mg/kg) or all-trans-retinoic acid (10 or 15 mg/kg) for 7 consecutive days. Blood was collected out to 8 hr after the last gavage on day 7. HPLC serum concentrations of 13-cis-retinoic acid, all-trans-retinoic acid, and 13-cis-4-oxo-retinoic acid were subjected to model independent pharmacokinetic analyses. Peak serum levels of 563 to 1640 ng/ml were observed for rats treated with 13-cis-retinoic acid at 1.5-2 hr after gavage. Peak serum levels of 183 to 267 ng/ml at 1.5 hr after gavage were observed for all-trans-retinoic acids. The elimination half-life of 13-cis-retinoic acid was about 1.5 hr while the elimination half-life of all-trans-retinoic acid was slightly longer. There were no sex differences for any parameter. Serum levels resulting from the 7.5 mg/kg 13-cis-retinoic acid were similar to those of human Accutane users.     

酒精所致精神障碍男性患者心肌酶活性及血尿酸变化分析简

目的獉獉：探讨酒精所致精神障碍男性患者心肌酶活性及血尿酸变化情况。方法獉獉：应用OLYMPUS AU400全自动生化分析仪,对酒精所致精神障碍的男性患者279例,分别于新入院及入院治疗4周后测定其心肌酶（CK、AST、LDH）及血尿酸（SUA）并与对照组进行比较分析。结果獉獉：酒精所致精神障碍男性患者的血清心肌酶活性及血尿酸明显高于对照组（P〈0.01）;新入院血尿酸增高的男性患者组心肌酶活性明显高于正常尿酸组（P〈0.01）。结论獉獉：酒精所致精神障碍男性患者伴有心肌酶活性及血尿酸异常,其中血尿酸增高的男性患者心肌酶活性明显高于血尿酸正常的男性患者。     

Decrease of gastrointestinal mucosal damage by salicyluric acid compared with salicylic acid in rabbits.

The gastrointestinal mucosal damage following the oral administration of salicylic acid or salicyluric acid was examined in rabbits using a scanning electron microscope. Six and 24 h after treatment with salicylic acid, morphological changes of gastric mucosa were recognized. In rabbits treated with salicyluric acid, however, severe damage in the gastric mucosa was not found after 24 h compared with the treatment with salicylic acid. Following the treatment with salicylic acid, some mucosal damage in the duodenum, jejunum and ileum was observed after 24 h. The surface character of the duodenal, jejunal, ileal, caecal and colonic mucosa were almost identical compared with the control following the treatment with salicyluric acid. It was reported that salicyluric acid is metabolized to salicylic acid by the intestinal microorganisms. From these results, it was suggested that prodrugs utilizing the metabolism of salicyluric acid to salicylic acid by intestinal microorganisms may be useful in reducing gastrointestinal mucosal damage.     

尿酸、NT-proBNP及hsCRP在慢性心力衰竭诊断中的临床价值

目的：探讨血尿酸、hsCRP及NT-proBNP在慢性心力衰竭（心衰）诊断方面的临床价值。方法选取41例慢性心衰患者及31例健康对照组,检测外周血尿酸、hsCRP及NT-proBNP的浓度,分析其与NYHA（纽约心脏病协会）心功能分级、LVEF（左室射血分数）及 LVEDD（左室舒张末期内径）的相关性。结果慢性心衰患者血尿酸、hsCRP 及 NT-proBNP 较对照组显著升高（ P ＜0.05）,不同心功能分级之间的血尿酸及NT-proBNP亦有统计学差异（P＜0.05）。尿酸及NT-proBNP与心功能分级及LVEDD呈正相关（r＝0.67,P＜0.05;r＝0.52,P＜0.05;r＝0.54,P＜0.05;r＝0.53,P＜0.05）,与LVEF呈负相关（r＝－0.61,P＜0.05;r＝－0.57,P＜0.05）。尿酸与NT-proBNP两者之间亦有一定的相关性（r＝0.46,P＜0.05）。结论慢性心衰患者血尿酸及NT-proBNP与疾病严重程度相关,是心功能评价的较好指标,而hsCRP在心衰诊断的临床价值不如尿酸及NT-proBNP。     

丙戊酸钠及其代谢产物与肝损伤的相关性分析

目的研究丙戊酸钠及3个代谢产物(2-丙基-4-五烯酸、3-羟基丙戊酸、5-羟基丙戊酸)对肝损伤参考指标的相关性分析。方法共收集328例癫痫患者血样,其中,123例肝功能异常癫痫患者血样为试验组,205例肝功能正常癫痫患者血样为对照组,采用LC-MS/MS方法测定两组血样(丙戊酸钠及代谢产物)的血药浓度,通过ROC曲线分析丙戊酸及其代谢产物浓度对肝功能异常的诊断价值。结果肝功能异常组患者丙戊酸钠及其3个代谢产物平均血药浓度均高于对照组,差异有统计学意义(P<0.05)。丙戊酸钠及其代谢产物的血药浓度均可作为诊断肝损伤的参考指标,5-羟基丙戊酸比丙戊酸钠有更好的诊断价值。结论丙戊酸钠代谢产物与肝毒性有关,能够作为肝损伤的诊断指标,可将其应用于临床,为丙戊酸钠有效给药提供参考。     

Montmorillonite adsorbs uric acid and increases the excretion of uric acid from the intestinal tract in mice

Objectives The aim was to evaluate the adsorbing effect of montmorillonite on uric acid, promoting diffusion of uric acid from blood to intestine, preventing absorption of uric acid in intestine and reducing uric acid level in serum. Methods The adsorbing effect of montmorillonite on uric acid was observed in vitro. The intestine and blood vessel of rats were circularly perfused with intestinal perfusate and vascular perfusate, respectively. A model of hyperuricaemia in mice was prepared by intraperitoneal injection of hypoxanthine and potassium oteracil. The concentration of uric acid was determined by the method of urate oxidase and peroxide enzyme. Key findings The results showed that different concentrations of montmorillonite could adsorb uric acid in a concentration‐dependent manner. The adsorbing effect was fast. The adsorptive rate was high in acid solution and was low in alkaline solution. When blood vessels were circularly perfused by vascular perfusate containing uric acid, the concentration of uric acid in vascular perfusate was decreased and the concentration of uric acid in intestinal perfusate was increased, suggesting that uric acid in blood vessels diffused into the intestine. When the intestine was perfused with intestinal perfusate containing uric acid, the uric acid concentration in vascular perfusate was increased, but the uric acid concentration of intestinal perfusate was decreased, suggesting that uric acid was absorbed in the intestine. The uric acid concentrations of intestinal perfusate and vascular perfusate in montmorillonite 0.5 and 1.0 g/kg groups were lower than the control group. Concentrations of uric acid in serum and urine in the montmorillonite 1 and 2 g/kg groups were lower compared with mice in the hyperuricaemic group. Conclusions The results suggested that montmorillonite adsorbed uric acid and promoted diffusion of uric acid from blood vessels to intestine, prevented absorption of uric acid in intestine and decreased uric acid level in serum.     

Interfering Peaks in Gas Chromatographic Exclusion Screening of Direct Chloroform Extracts of Blood*

The abilities of 24 endogenous biochemicals to interfere with gas chromatographic exclusion screening analyses for drugs of direct chloroform extracts obtained from forensic blood specimens were studied. The relative retention on OV -17 of the 24 endogenous compounds and the direct extract-abilities of 8 of these were compared with those of 30 directly extractable acidic, phenolic, neutral and basic drugs. On direct extracts of blood, gas chromatographic peaks were obtained with phenylethylamine, 5-hydroxymethylfurfural, p-hydroxybenzaldehyde, p-hydroxybenzoic acid, p-hydroxyphenylacetic acid and stearic acid. Palmitic acid and p-hydroxyphenylpropionic acid were not directly extractable, while no gas chromatographic peaks were obtained with three neutral lipids, cholesterol, four cholesterol esters, deoxycholic acid, phosphatidyl-L-serine, heparin and L-glutamine. Tyramine, tryptamine, tristearin and lysolecithin gave gas chromatographic peaks but their direct extractabilities were not determined. Post mortem toxicological cases are described in which apparent barbiturate, tripelennamine, hydroxyglutethimide and desipramine gas chromatographic peaks were probably mimicked by stearic acid, p-hydroxybenzaldehyde and/or tryptamine; differentiations were effected by selective washing of the chloroform extracts with weak and strong bases, acid, ammoniacal AgNO₃ and aqueous NaHSO₃.