抗感颗粒联合奥司他韦治疗小儿流行性感冒的临床研究

目的探讨抗感颗粒联合奥司他韦治疗小儿流行性感冒的临床效果。方法选取2016年6月—2018年12月亳州市人民医院收治的62例流行性感冒患儿,按照随机数字表法随机分为对照组和治疗组,每组各31例。对照组口服磷酸奥司他韦颗粒,体质量≤15 kg者,30 mg/次,2次/d;15～23 kg者,45 mg/次,2次/d;23～40 kg者,60 mg/次,2次/d;40kg者,75mg/次,2次/d。治疗组在对照组治疗基础上口服抗感颗粒,1～5岁者,0.5袋/次,3次/d;6～9岁者,1袋/次,3次/d;10～14岁者,1.5袋/次,3次/d;开水冲服。两组患儿均连续治疗5 d。观察两组的临床疗效,比较两组主要症状积分、症状改善时间、血象情况和C反应蛋白的变化情况。结果治疗后,对照组和治疗组的总有效率分别是80.65%、100.0%,两组比较差异具有统计学意义(P0.05)。治疗后,两组发热积分、咽黏膜充血积分、咳嗽积分、咳痰黄稠积分均较治疗前显著降低,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组这些症状积分显著低于对照组,两组比较差异有统计学意义(P0.05)。治疗后,对照组和治疗组的即刻退热率分别是35.5%、61.3%,两组比较差异具有统计学意义(P0.05);治疗组起效时间和体温恢复正常时间均显著短于对照组,两组比较差异具统计学意义(P0.05)。治疗后,两组白细胞总数(TWBC)、中性粒细胞比例(NETU%)异常例数和异常率均较治疗前显著降低,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组TWBC、NETU%异常例数和异常率显著低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组C反应蛋白(CRP)较治疗前显著降低,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组CRP水平显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论抗感颗粒联合奥司他韦治疗小儿流行性感冒具有较好的临床疗效,可明显减轻患儿风热犯表证的相关症状,退热效果显著,具有一定的临床推广应用价值。     

Effect of buffer conditions on CYP2C8-mediated paclitaxel 6α-hydroxylation and CYP3A4-mediated triazolam α- and 4-hydroxylation by human liver microsomes

Abstract

1.?Buffer conditions in in vitro metabolism studies using human liver microsomes (HLM) have been reported to affect the metabolic activities of several cytochrome P450 (CYP) isozymes in different ways, although there are no reports about the dependence of CYP2C8 activity on buffer conditions.

2.?The present study investigated the effect of buffer components (phosphate or Tris-HCl) and their concentration (10–200?mM) on the CYP2C8 and CYP3A4 activities of HLM, using paclitaxel and triazolam, respectively, as marker substrates.

3.?The K_m (or S₅₀) and V_max values for both paclitaxel 6α-hydroxylation and triazolam α- and 4-hydroxylation, estimated by fitting analyses based on the Michaelis–Menten or Hill equation, greatly depended on the buffer components and their concentration.

4.?The CL_int values in phosphate buffer were 1.2–3.0-fold (paclitaxel) or 3.1–6.4-fold (triazolam) higher than in Tris-HCl buffer at 50–100?mM. These values also depended on the buffer concentration, with a maximum 2.3-fold difference observed between 50 and 100?mM which are both commonly used in drug metabolism studies.

5.?These findings suggest the necessity for optimization of the buffer conditions in the quantitative evaluation of metabolic clearances, such as in vitro–in vivo extrapolation and also estimating the contribution of a particular enzyme in drug metabolism.     

Phosphate buffer interferes dissolution of prazosin hydrochloride in compendial dissolution testing

The purpose of this study was to elucidate the lack of supersaturation behavior in the dissolution profile of prazosin hydrochloride (PRZ-HCl) in the compendial dissolution test. The equilibrium solubility was measured by a shake-flask method. Dissolution tests were performed by a compendial paddle method with a phosphate buffer solution (pH 6.8, 50 mM phosphate). The solid form of the residual particles was identified by Raman spectroscopy. In the pH range below 6.5, the equilibrium solubility in phosphate buffer was lower than that in the unbuffered solutions (pH adjusted by HCl and NaOH). Raman spectra showed that the residual solid was a phosphate salt of PRZ. In the pH range above 6.5, the pH-solubility profiles in the phosphate buffer solutions and the unbuffered solutions were the same. The residual solid was a PRZ freebase (PRZ-FB). In the dissolution test, PRZ-HCl particles first changed to a phosphate salt within 5 min, then gradually changed to PRZ-FB after several hours. Since the intestinal fluid is buffered by the bicarbonate system in vivo, the dissolution behavior in vivo may not be properly evaluated using a phosphate buffer solution. For drugs with a low phosphate solubility product, it is necessary to consider this aspect.     

当归苦参丸联合克林霉素磷酸酯凝胶治疗玫瑰痤疮的临床研究

目的 探讨当归苦参丸联合克林霉素磷酸酯凝胶治疗玫瑰痤疮的临床疗效。方法 选择2019年11月—2022年8月天津市北辰医院收治120例玫瑰痤疮者,随机分为对照组（60例）和治疗组（60例）。对照组患者外涂克林霉素磷酸酯凝胶,2次/d。在对照组的基础上,治疗组口服当归苦参丸,6 g/次,2次/d。两组服药8周。观察两组患者临床疗效,比较治疗前后两组患者症状缓解时间,皮肤病生活质量量表（DLQI）,血清炎性因子肿瘤坏死因子-α（TNF-α）、抗菌肽-37（LL-37）、白细胞介素-6（IL-6）和干扰素-γ（INF-γ）水平及不良反应情况。结果 治疗后,治疗组患者临床有效率为98.33%,明显高于对照组（83.33%,P＜0.05）。治疗后,治疗组患者症状缓解时间均早于对照组（P＜0.05）。治疗后,两组患者DLQI评分均明显下降（P＜0.05）,且治疗组的DLQI评分低于对照组（P＜0.05）。治疗后,两组患者LL-37、IL-6、TNF-α水平均低于治疗前,而IFN-γ水平高于治疗前（P＜0.05）,且治疗组血清炎性因子水平明显好于对照组（P＜0.05）。治疗后,治疗组不良反应发生率（5.00%）明显低于对照组（11.67%,P＜0.05）。结论 当归苦参丸联合克林霉素磷酸酯凝胶治疗玫瑰痤疮效果确切,可显著改善症状,有效降低炎性反应。     

Glutamic dehydrogenase from rat heart mitochondria. II. Kinetic characteristics

Glutamic dehydrogenase purified from rat heart mitochondria has been characterized with regard to its substrate kinetics and the influence of nucleotides and potassium phosphate on its kinetic properties. The enzyme had characteristics similar to liver mitochondrial glutamic dehydrogenase. These included several double reciprocal plots which were biphasic, indicating homotropic interaction; inhibition by GTP, which was overcome by ADP and phosphate; and activity with both NAD(H) and NADP(H). There were a number of significant differences however, in the specific kinetic properties of heart mitochondrial glutamic dehydrogenase. The Vmax of reductive amination was four-fold greater with NADH than with NADPH. The maximum rate of oxidative deamination was ten-fold greater with NAD compared to NADP. The differences also included: saturating levels of NADH and NADPH were stimulatory rather than inhibitory; ammonia was stimulatory at millimolar levels; NADP and alpha-ketoglutarate were both inhibitory at saturating levels; and ADP increased reductive amination 30% at lower levels of NADH but inhibited at higher (stimulatory) levels of NADH.     

Ligustilide inhibits tumour necrosis factor-alpha-induced autophagy during C2C12 cells differentiation

Ligustilide is widely thought to be the most potent bioactive constituent of Angelica sinensis. We have previously reported the role of ligustilide in preventing TNF-α-induced apoptosis and identified the presence of autophagosome clusters. Then, we hypothesised that autophagy may contribute to muscle loss and that ligustilide could protect cell fibres by regulating the autophagic process. The aim of this study was to identify the effects of ligustilide on autophagy regulation during cell differentiation in the presence of TNF-α. We then observed intracellular morphologic changes and autophagosome formation using transmission electron microscopy. LC3B expression was assessed by immunofluorescence and Atg-7, Atg-5, Atg-12 and LC3B expression levels were detected by western blot. The results revealed a reduction in the number of TNF-α-induced autophagosomes after ligustilide treatment accompanied by a decrease in Atg-7, Atg-5, Atg-12 and LC3B expression, as well as a reduction of the LC3BII/I ratio in a concentration-dependent manner. Our findings provide evidence supporting a protective effect of ligustilide against TNF-α-induced autophagy during myotubes formation.     

Le cyclophosphamide dans le syndrome néphrotique idiopathique : résultats et perspectives

IntroductionCyclophosphamide (CYP) has been used for over 40 years in patients with steroid-sensitive nephrotic syndrome (NSSS) presenting frequent relapses (NSRF) or steroid dependence (NSSD). However, the long-term success of treatment with cyclophosphamide is difficult to predict. The objectives of this study are to determine long-term outcomes of cyclophosphamide and identify the factors associated with sustained remission.MethodsWe retrospectively studied the data from 50 patients with idiopathic nephrotic syndrome, treated by oral cyclophosphamide and followed at service of pediatric for more than 8 years for idiopathic nephrotic syndrome and related factors for survival without relapse were evaluated by univariate analysis.ResultsThe median age at the time of diagnosis was 4.3 years, and median follow-up time was 1.7 years with the median of 8 years at the first use of CYC. Patients had received a median cumulative dose of 168 mg/kg. At the end of follow-up, 38% of patients entered into remission after using CYC while 62% failed to respond and further relapses then occur. The median time of stopping corticosteroid therapy was three month. The survival without relapse was respectively 56% (28 patients), 52% (26 patients), 48% (24 patients), and 38% (19 patients), at 6 months, one year, two years and more than two years. In univariate analysis, the survival without relapse was related to the age at the moment of starting the therapy par CYC (the median was 5 months for an age  <  8 years and 41 months for an age ≥ 8 years; P = 0.049), the type of nephrotic syndrome [36 months for SNRF, 4 months for NSSD and nephrothic syndrome steroid resistant (NSSR); P = 0.068], and the histological lesion (6 months for diffuse mesangial proliferation, 2 months for segmental glomerulosclerosis; P = 0.009). The age at the moment of diagnosis, the sex and the cumulative dose of CYC did not have significant influence.ConclusionThe results presented in this study suggest the use of oral cyclophosphamide for short period remain second line effective therapy. Further well-designed trials are required to evaluate the efficacy of other steroid-sparing agents.     

复方环磷腺苷乳膏对银屑病动物模型作用的实验研究

目的研究复方环磷腺苷乳膏对银屑病动物模型的治疗作用。方法采用小鼠阴道上皮和豚鼠耳部皮肤银屑病样皮损模型，观察复方环磷腺苷乳膏对上皮细胞分裂及表皮细胞分化的影响。结果复方环磷腺苷乳膏能明显抑制阴道上皮细胞有丝分裂、使豚鼠银屑病样模型耳部皮肤厚度显著减少。结论复方环磷腺苷乳膏治疗银屑病可能有效。     

磷酸酯单体PENTA与牙科氧化锆陶瓷结合的化学证据

目的 提供磷酸酯单体双季戊四醇五丙烯酸酯磷酸酯（Dipentaerythritol penta-acrylate phosphate,PENTA）与牙科氧化锆陶瓷结合的化学证据,分析PENTA提高牙科氧化锆陶瓷粘接的机理。 方法 配置包含PENTA的质量分数为5%、10%、15%、20%的实验性底涂剂,用其处理Y-TZP（Yttria-stabilized tetragonal zirconia polycrystals）瓷粉,随后以丙酮反复清洗去除游离成分后分别进行红外光谱分析（fourier transform infrared spectroscopy,FTIR）和热重分析（thermogravimetric analysis,TG）。FTIR分析以10%PENTA丙酮溶液作为对照,分别采用二阶导数分峰和残差分峰两种方法对FTIR图谱磷酸基团特征峰进行分峰分析;TG以空白Y-TZP粉作为对照。 结果 两种FTIR分峰分析结果一致,均表明各种浓度的包含PENTA的底涂剂与Y-TZP陶瓷接触后,磷酸基团的P-O键振动所产生的波峰向波数减小的方向移动。热重结果证明PENTA能够化学吸附于Y-TZP表面,高浓度组的PENTA与氧化锆的反应程度更高。 结论 PENTA能够与Y-TZP发生化学结合,该化学反应的存在依赖于PENTA分子中的磷酸基团发挥作用。