复方盐酸苯海拉明凝胶的制备与质量控制

目的 研制复方盐酸苯海拉明凝胶,并建立其质量控制方法. 方法 以卡波姆作为凝胶基质,制备复方盐酸苯海拉明凝胶,采用高效液相色谱法进行含量测定. 结果 制备的凝胶均匀细腻,稳定性好;盐酸苯海拉明检测浓度在100～500 μg• mL^-1 范围内线性关系良好（r＝0.999 9）,平均回收率为100.41%,RSD＝0.87%;地塞米松磷酸钠检测浓度在10～50 μg•mL^-1范围内线性关系良好（r＝0.999 4）,平均回收率为100.96%,RSD＝1.15%. 结论 该凝胶制备工艺简单,质量稳定,质量控制方法准确可靠.     

高效液相色谱法测定奥硝唑凝胶中奥硝唑的含量

目的 采用高效液相色谱(HPLC)法测定奥硝唑凝胶中奥硝唑的含量. 方法 采用ODS C₁₈(4.6 mm×150 mm,5 μm) 的色谱柱;流动相：乙腈－水（20：80）,检测波长：312nm,流速：1 mL•min^-1,塞克硝唑为内标. 结果 奥硝唑浓度在0.63～20.00 μg•mL^-1范围内,峰面积与峰面积/内标比值具有良好线性关系,r＝0.999 9,平均回收率100.2%,RSD=1.2%. 结论 该法建立的含量测定方法 操作简便, 结果 准确、灵敏.     

腺苷钴胺凝胶中腺苷钴胺的含量测定

目的 采用高效液相色谱(HPLC)法测定腺苷钴胺凝胶中的腺苷钴胺含量. 方法色谱柱为Uitimate Column XB C₁₈(4.6 mm×250 mm,5 μm),以0.05 mol.L^-1磷酸二氢钾溶液(用磷酸调节pH为3.2)-乙腈(83:17)为流动相;柱温:35 ℃;进样量:10 μL;流速:1.0 mL.min^-1,检测波长:260 nm. 结果 腺苷钴胺在10～50 μg.mL^-1范围内线性关系良好(r＝0.999 9),平均回收率为99.49%,RSD为0.60%(n＝9). 结论 该方法专属性强、准确,可用于测定腺苷钴胺凝胶的含量.     

高效液相色谱法测定复方醋酸地塞米松搽剂中醋酸地塞米松的含量

目的 建立高效液相色谱法测定复方醋酸地塞米松搽剂中醋酸地塞米松的含量. 方法 Agilent TC-C₁₈色谱柱（4.6 mm×150 mm,5 μm）;流动相：甲醇-水（70：30）;流速：1.0 mL&;#8226;min^-1;检测波长：240 nm. 结果 醋酸地塞米松在2.02～60.60 mg&;#8226;L^-1的浓度范围内线性关系良好（r＝0.999 5）,平均回收率为101.11%,RSD＝0.80% （n＝9）. 结论 该法操作简便,结果准确,精密度好,可用于复方醋酸地塞米松搽剂的质量控制.     

高效液相色谱法测定野木瓜中绿原酸的含量

目的 建立野木瓜中绿原酸的含量测定方法. 方法 用高效液相色谱法测定绿原酸的含量,色谱柱：Diamonsil C^₁₈柱（4.6 mm×250 mm,5 μm）,流动相：乙腈-0.1%磷酸（11：89）,流速：1 mL•min^-1,测定波长：327 nm. 结果 平均回收率98.2%（RSD＝1.1% ,n＝6）,绿原酸在9.6～192.0 μg•mL-1呈良好线性关系,r＝0.999 9,精密度RSD＝1.1%,重复性RSD＝1.5%（n＝6）. 结论 该方法稳定、可靠,可作为该药材的质量控制方法.     

小儿消咳片中白屈菜红碱的含量测定

目的 建立高效液相色谱(HPLC)法测定小儿消咳片中白屈菜红碱的含量测定方法. 方法采用HPLC法,色谱柱:Zorbax SB C₁₈(250 mm×4.6 mm,5 μm),流动相:乙腈 1%三乙胺溶液(磷酸调pH为3.0)(25:75),检测波长:269 nm;流速1.0 mL.min^-1,进样量10 μL. 结果 白屈菜红碱在8.25～825.00 μg.mL^-1范围内线性关系良好(r＝0.999 8),平均加样回收率为96.80%,RSD为1.11%(n＝6). 结论 该方法简便快捷,准确,重复性好,灵敏度高,可用于小儿消咳片的质量控制.     

高效液相色谱法测定牛黄解毒滴丸中大黄素和大黄酚含量

目的 采用高效液相色谱法测定牛黄解毒滴丸中大黄素和大黄酚含量. 方法色谱柱:Kromasil C₁₈柱(4.6 mm×150 mm,5 μm);流动相:甲醇-0.1%磷酸溶液(85:15);流速:1 mL•min^-1;紫外检测波长:254 nm;柱温:30 ℃. 结果 大黄素在2.36～37.72 μg•mL^-1范围内线性关系良好,平均回收率分别为99.56%,RSD=1.1%(n＝9);大黄酚在6.41～102.60 μg•mL-1范围内线性关系良好,平均回收率99.89%,RSD=1.8%(n＝9). 结论 该方法简便,准确,可作为牛黄解毒滴丸质量控制的方法.     

高效液相色谱法测定复方磷酸可待因口服液中3种有效成分的含量

目的 建立高效液相色谱法测定复方磷酸可待因口服液盐酸麻黄碱、磷酸可待因、马来酸氯苯那敏的含量. 方法 采用高效液相色谱法,色谱柱:C18(250 mm×4.6 mm,5 μm);流动相:甲醇-水-三乙胺-高氯酸钠(650:350:2:2);检测波长:261 nm;流速:1.0 mL.min^-1;柱温:35 ℃;进样量:20 μL. 结果 盐酸麻黄碱在0.051～0.463 mg.mL^-1线性关系良好(r=0.999 9),平均回收率98.9%,RSD=0.63%;磷酸可待因在0.039～0.355 mg.mL^-1线性关系良好(r=1.000 0),平均回收率100.4%,RSD=0.95%;马来酸氯苯那敏在0.032～0.285 mg.mL^-1线性关系良好(r=0.999 9),平均回收率100.7%,RSD=0.93%. 结论 该方法 操作简单、准确,可同时测定复方磷酸可待因口服液盐酸麻黄碱、磷酸可待因、马来酸氯苯那敏的含量,有效控制处方质量.     

复方当归微乳中桂皮醛和藁苯内酯的含量测定

目的 建立高效液相色谱(HPLC)法测定复方当归微乳中主成分藁苯内酯和桂皮醛的含量,为其质量标准的建立提供依据. 方法 色谱柱为Inertsil ODS 3柱(4.6 mm×150 mm,5 μm),流动相为乙腈-水(55：45),流速1.0 mL.min^-1,检测波长：285 nm,柱温30 ℃. 结果桂皮醛在0.484 5～38.750 0 μg.mL^-1浓度范围内呈良好的线性关系,回归方程为Y＝27.060X-1.586 (r＝0.999 8),加样回收率为99.60%,日内和日间精密度RSD低于1.25%;藁本内酯在0.531 0～106.100 0 μg.mL^-1范围内线性关系良好,回归方程为Y＝13.930X＋1.344(r＝0.999 8),加样回收率为98.92%,日内和日间精密度RSD低于1.25%. 结论 建立的HPLC法专属性强、灵敏度高,可用于复方当归微乳的质量控制.     

反相高效液相色谱法测定唑克搽剂中盐酸克林霉素的含量

目的建立反相高效液相色谱法测定唑克搽剂中盐酸克林霉素含量的方法。方法色谱柱为Kromail C18柱(4.6 mm×250 mm，5 μm)；柱温：40 ℃；流动相为水-甲醇(21∶30)，含0.02 mol·L^-1磷酸二氢铵和0.01 mol·L^-1乙二胺四醋酸二钠，并以4 mol·L^-1磷酸溶液调节pH值至3.0；流速0.9 mL·min^-1；检测波长为367 nm。结果盐酸克林霉素在10～100 μg·mL^-1的范围内线性关系良好，r＝0.999 6(n＝6)，平均回收率为99.40 %(n＝6)，RSD为1.0 %。结论该方法简便、快速、准确，可用于唑克搽剂的质量控制。     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

Isolation and characterization of glycosylated and non-glycosylated prolactins from alligator and crocodile

Two molecular forms of prolactin (PRL). glycosylated and non-glycosylated, were isolated from pituitary glands of two reptiles, alligator and crocodile. The reptilian PRLs were extracted under alkaline conditions from the precipitate obtained after pituitaries were first extracted with 0.25 m sucrose, 1 mM NH₄HCO₃, pH 6.3. Purification was performed by ion exchange chromatography on DE-52, gel filtration on Sephadex G-75 superfine, and reversed phase high performance liquid chromatography. Two forms of both alligator and crocodile PRL, designated PRLI and PRLII, with molecular weights of 26000 and 24000 were isolated. Alligator and crocodile PRLI and PRLII were stained specifically in immunoblots with anti-sea turtle PRL and anti-ostrich PRL. Sequence analysis revealed that both forms of alligator and crocodile PRLs consisted of 199 amino acid residues with a glycosylation consensus sequence (Asn-Ala-Ser) at position 60 in alligator and crocodile PRLs with a molecular weight of 26000 (PRLI). In contrast, Thr was substituted for Asn at position 60 in the PRLs with a molecular weight of 24000 (PRLII). The sequences of alligator PRLs differed from crocodile PRLs only in position 134: Val for alligator PRLs and He for crocodile PRLs. There is a high degree of structural conservation between the reptilian PRLs isolated in this study and avian PRL; each showed 92% sequence identity with chicken PRL and 89% with turkey PRL.     

Pharmacokinetics and pharmacodynamics of ramipril and piretanide administered alone and in combination

The pharmacokinetics and pharmacodynamics of single oral doses of 5 mg ramipril and 6 mg piretanide administered separately and in combination were determined in a single blind, randomised, 3-period cross-over study in 24 healthy male volunteers.The peak plasma concentrations of ramipril and ramiprilat increased slightly (from 11.9 to 14.8 ng/ml, and from 6.39 to 8.96 ng/ml, respectively) as did the area under the plasma concentration-time curve of ramipril (0–4 h) and ramiprilat (0–24 h) (from 15.8 to 19.8 ng·ml^–1·h, and from 63.4 to 74.6 ng·ml^–1·h, respectively). The urinary excretion of ramiprilat also rose (from 6.82 to 7.73 % of dose) following simultaneous treatment with piretanide. These effects were probably due to reduced first-pass metabolism of ramipril/ramiprilat to inactive metabolites. The blood pressure lowering effect, the time course of inhibition of ACE activity in plasma and the concentration-response relationship for the inhibition of plasma ACE activity were not affected by piretanide.The peak plasma concentration of piretanide was somewhat reduced (from 285 to 244 ng/ml) following simultaneous treatment with ramipril. No other pharmacokinetic parameter was affected. Piretanide increased urine flow, and sodium, chloride and potassium excretion, especially during the first 2 hours following administration. These pharmacodynamic parameters were not affected by ramipril.Thus, simultaneous administration of single oral doses of ramipril and piretanide caused modest changes in the peak and average plasma concentrations of both drugs, which did not lead to detectable alterations in the pharmacodynamic parameters measured in healthy volunteers.     

Benzodiazepines,amnesia and sedation: Theoretical and clinical issues and controversies

The amnestic effect of benzodiazepines, first described in 1965, and the subsequent attempts to identify the precise nature of this effect, are reviewed. The difficulty in deciding to what extent this effect is secondary to the sedative action of these drugs is shown by the lack of agreement between studies. Nevertheless, it is concluded that, given the right experimental design, all benzodiazepines can be shown to cause an anterograde amnesia which is probably primarily a result of reduced attention or rehearsal and secondary to sedation. Its onset, degree and duration are influenced by dose, rate of absorption, route of administration, potency and the receptor occupancy rate of the particular benzodiazepine involved, but plasma elimination t_½ appears to be relatively unimportant. The clinical relevance of this for the long-term use of hypnotics and anxiolytics is not clear. Tolerance appears to be greater than for the anxiolytic but less than the sedative or anticonvulsant effect of benzodiazepines. It seems that transient amnestic effects could occur in chronic users related to post-dose, peak benzodiazepine levels. The great variability in individual response means that transient amnesia is a potential adverse drug reaction in certain individuals taking benzodiazepines.