Pharmacokinetics of the placental transfer and distribution of clorazepate and its metabolite nordiazepam in the feto-placental unit and in the neonate

Summary Clorazepate 20mg was given i. m. to 49 mothers during the first stage of labour. The elimination of the drug was studied in 27 newborns produced by these mothers. The same dose was given to 13 women who underwent amniocentesis and to 7 women who were breast-feeding. Total nordiazepam, i.e. the sum of clorazepate and its metabolite nordiazepam, was determined by gas-liquid chromatography in maternal blood, umbilical cord blood (both arterial and venous), amniotic fluid and in milk. Clorazepate was found to cross the placental barrier slowly, but nordiazepam was transferred more rapidly. Nordiazepam was found in the milk and in the blood of neonates after breast-feeding had started.     

血细胞检测流水线系统对白细胞形态的影响

目的探讨XN-9000全自动血细胞检测流水线系统对白细胞形态的影响。方法采用乙二胺四乙酸二钾(EDTA-K 2)专用负压管对空军军医大学西京医院和西安培华学院医学院收集的238例受试者(其中淋巴细胞性白血病26例、粒细胞性白血病17例、单核细胞性白血病15例、健康儿童80例、健康成人100例)采集静脉血2 mL,采用XN-9000全自动血细胞检测流水线系统在1 h内完成推片、瑞姬染色、阅片,同时采用手工推片、手工瑞姬染色,由两位经验丰富的主管技师进行显微镜分类计数。结果238例受试者EDTA-K 2抗凝血仪器推片后分别采用仪器染色和手工染色分类计数Ⅱ型反应性淋巴细胞结果[(8.65±2.35)%、(8.55±2.45)%]明显高于手工推片仪器染色和手工推片手工染色结果[(4.57±2.55)%、(4.67±2.45)%],差异有统计学意义(P<0.05)。健康对照者(健康儿童及成人)、粒细胞性白血病和单核细胞性白血病患者抗凝血经仪器推片分类计数Ⅱ型反应性淋巴细胞分别为(3.2±0.5)%、(3.5±0.4)%、(3.6±0.5)%,与手工推片结果[(3.1±0.8)%、(3.2±0.6)%和(3.4±0.8)%]比较,差异无统计学意义(P>0.05)。淋巴细胞性白血病患者淋巴细胞形态有明显改变:淋巴细胞体积增大,外形不规则,着色不均,边缘蓝色较深,细胞核不规则,染色质细致,细胞质呈淡紫红色,似Ⅱ型(不规则型/单核细胞型)反应性淋巴细胞。淋巴细胞性白血病患者Ⅱ型反应性淋巴细胞的仪器推片结果为(85.2±5.6)%,与手工推片结果[(3.5±0.9)%]比较,差异有统计学意义(P<0.05)。结论XN-9000全自动血细胞检测流水线系统对EDTA-K 2抗凝血活化膨胀的白细胞无法调节推片力度,加之白血病患者的血细胞密度高、阻力大而致细胞形态改变,使淋巴细胞似Ⅱ型反应性淋巴细胞,影响临床对疾病的诊断。手工推片可调节角度、速度及力度,细胞形态不易改变。当Ⅱ型反应性淋巴细胞多时,必须手工推片手工染色,显微镜检查确证后方可发报告。     

Upregulated expression of human alpha-defensins 1, 2 and 3 in hypercholesteremia and its relationship with serum lipid levels

Human alpha-defensins are natural antimicrobial peptides of neutrophils evolved in host defense reactions and circulating nonstressed alpha-defensins may be associated with serum lipid levels. The aim of this work was to examine whether the expression of alpha-defensins 1, 2 and 3 genes are changed and whether this changes are reversed following treatment in patients with hypercholesteremia. A total of 40 individuals of hypercholesteremia group were studied, compared with 40 individuals of normal control group. Protein levels and gene expression levels of alpha-defensins 1, 2 and 3 were significantly higher in patients with hypercholesteremia compared with subjects in normal control group. In patients with hypercholesteremia, protein levels of alpha-defensins 1, 2 and 3 correlated positively with the levels of total cholesterol and low-density lipoprotein cholesterol. Protein levels and gene expression levels of alpha-defensins 1, 2 and 3 were decreased significantly after a treatment with atorvastatin calcium 20 mg daily compared with the patients before the treatment. Our results suggest that the expression of alpha-defensins 1, 2 and 3 genes is involved in dyslipidemia in patients with hypercholesteremia.     

Chitosan-dipotassium orthophosphate lyophilizate: a novel in situ thermogel carrier system of allogeneic platelet lysate growth factors

The clinical success of platelet-rich plasma (PRP) is constrained by its limited mechanical strength, rapid disintegration by lytic enzymes, and the consequent short-term release of bioactive growth factors (GFs). Recently, attempts to formulate PRP and other hemoderivatives, such as platelet lysate (PL) have been underway. The current study aimed to formulate allogeneic freeze-dried human platelet lysate (HPL) onto lyophilized chitosan - dipotassium hydrogen orthophosphate (CS/DHO) thermo-sensitive scaffolds. A systemic approach was employed to optimize freeze-drying (FD) procedures targeting predefined critical quality attributes (CQAs). Thermal behavior, vibrational spectroscopy, morphological and moisture content analyses were used to detect possible protein destabilization during formulation and suboptimal cake properties. The effect of CS/DHO concentrations on thermo-responsiveness and release kinetics were investigated. Finally, six-months stability and cytotoxicity studies were carried out. An optimized lyophilizate was attainable with residual moisture of less than 5% and thermoresponsive to 33 °C in less than 3 min. HPL proteins were sustainedly released over five days in a pH-sensitive manner. The stability study indicated plausible physical and biochemical stability. Cell viability testing supported the cytocompatibility of the system. Finally, the lyophilizate variant of CS/DHO thermogel overcomes limited storage stability previously posed as a challenge in freshly prepared thermogels. The developed system overcomes the drawbacks of currently used PRP treatment and provides a novel GF-rich scaffold for wound repair.     

Prolonged sedation requiring mechanical ventilation and continuous flumazenil infusion after routine doses of clorazepam for alcohol withdrawal syndrome

We report the cases of two patients who developed prolonged sedation after routine doses of clorazepam for alcohol withdrawal syndrome. They required prolonged mechanical ventilation (10 days for both patients) followed by continuous flumazenil infusion (16 days for one patient and 3 days for the other) to avoid reintubation. In the two patients, nordazepam accumulation (main active metabolite of clorazepam) was demonstrated as the cause of the coma. This accumulation could be attributed, in one case, to impaired hepatic cytochrome P 450 3A4 activity. Caution is required when prescribing benzodiazepines to alcoholic patients and the use of benzodiazepine which do not undergo hepatic oxidation by cytochrome P 450 such as oxazepam or lorazepam is suggested. Received: 9 February 1999 Final revision received: 7 October 1999 Accepted: 13 October 1999     

3厂家复方门冬维甘滴眼液中抑菌剂的抑菌效力考察

目的:考察3厂家复方门冬维甘滴眼液中抑菌剂的抑菌效力。方法:采用菌落计数法,以pH7.0氯化钠-蛋白胨缓冲液为对照,测定3厂家复方门冬维甘滴眼液抑菌剂对金黄色葡萄球菌、大肠埃希菌、铜绿假单胞菌、白色念珠菌及黑曲霉作用不同时间(0、7、14、28d)后的活菌数,以菌落的对数下降值为指标,评价抑菌效力。结果:3厂家复方门冬维甘滴眼液中上述各菌第7天的菌落对数下降值均在5.00～5.94范围内,第14、28天均在5.68～5.94范围内。结论:3厂家复方门冬维甘滴眼液抑菌剂的抑菌效力均符合《中国药典》标准眼用制剂要求。     

Delusional misidentification of the Capgras and intermetamorphosis types responding to clorazepate. A case report

A patient with chronic psychosis and intermittent psychotic misidentification of the Capgras and intermetamorphosis types refractory to neuroleptic treatment was given a trial of clorazepate. Complete remission of psychotic symptoms was achieved for the first time in 19 years, but these recurred when the patient discontinued her clorazepate. It is concluded that clorazepate may be a useful treatment for some cases of chronic psychosis and psychotic misidentification. A possible mechanism for this is discussed.     

四(二氯异氰尿酸)锌钾合成与杀菌作用的研究

在实验室内合成新型饮水消毒剂四(二氯异氰尿酸)锌钾,含有效氯57％左右。初步研究表明,该消毒剂稀释液对大肠杆菌有良好杀菌效果,并具有制备方法简单,得率高,氯刺激性气味小,吸潮性低,较二氯异氰尿酸钠稳定等优点。     

Transfer in vitro of three benzodiazepines across the human placenta

Summary A comparative study of the placental transfer to the foetus of three benzodiazepines was performed using a dual perfusion system of the human placental lobule. A transport fraction was calculated for each benzodiazepine and was compared with reference substances. Relative to antipyrine, the transport fraction of diazepam was 85%, and that of nordiazepam was 84%. The transport fraction of clorazepate represented only 20% of that of tritiated water. The relatively high transfer of diazepam and nordiazepam can be attributed to their high lipid solubility, and the lower transfer of clorazepate is due to its polar nature. It is suggested that in certain instances this benzodiazepine may be of especial value to obstetricians.Michèle Guerre-Millo is an M.S. aided by D.G.R.S.T.     

Pharmacokinetics of clorazepate in pregnant and non-pregnant women

Summary A single dose of clorazepate 20 mg was injected i.m. in 7 pregnant and 7 non-pregnant women. Blood samples were collected for one week, and urine was collected for 24 h after the dose. The concentrations of clorazepate and its metabolite nordiazepam were determined by electron capture gas liquid chromatography. There was no difference between the two groups on physical examinations. Clorazepate was rapidly absorbed and the peak concentration was reached within 2h. Mean pharmacokinetic parameters for clorazepate were absorption half life 0.77h in pregnant women and 0.56h in non-pregnant women; elimination half life 1.3h in pregnant women and 2.0h in non-pregnant women; volume of distribution: 0.43 l · kg^–1 in the pregnant women and 0.33 l · kg^–1 in non-pregnant women. Nordiazepam reached its peak concentration within 12h after dosing; its mean half life of elimination was 180h in pregnant women and 60h in non-pregnant women. Within 24h, 1.3% of the clorazepate was recovered in urine from pregnant women and 7% in urine from the non-pregnant women.