阿奇霉素凝胶的制备及质量控制

目的：建立阿奇霉素凝胶的制备及质量控制方法。方法：用卡波姆－940作凝胶基质制备阿奇霉素凝胶。进行了酸碱度及卫生学、稳定性、透皮吸收、皮肤刺激性等试验及含量测定。结果：pH值6．5－7．5,卫生学检查符合规定，凝胶稳定无变化无刺激性，含量测定平均回收率为100．7％。结论：本方法设计合理，稳定性好，可满足临床需要。     

司氟沙星凝胶的制备与质量考察

目的：研究司氟沙星凝胶。方法：用卡波姆－９４０作凝胶基质制备司氟沙星凝胶,建立了酸碱度、卫生学、含量测定等质量控制标准,对制剂进行了质量控制。结果：ｐＨ值７．０～８．０,卫生学检查符合规定,含量测定平均回收率为１００．５２％,ＲＳＤ为２．１１％（ｎ＝５）,并且凝胶稳定无变化。结论：本方法设计合理,稳定性好,疗效好,尚无不良反应,值得临床推广应用。     

依沙吖啶凝胶的制备与质控研究

目的：研制能增加用药部位药物浓度的依沙吖啶凝胶。方法：用ＣＭＣＮａ作凝胶基质,按制剂学原理制备了依沙吖啶凝胶,建立了酸碱度、卫生学、含量测定等质控方法,进行了加速试验和自然室温留样考察。结果：ｐＨ值６．５～６．８,卫生学检查符合规定,含量测定平均回收率９９．３４％,ＲＳＤ＝０．７４％（ｎ＝５）,并且凝胶稳定无变化。结论：制备该凝胶工艺简单,所得制剂质量可控,性质稳定,可满足临床用药需求。     

复方替硝唑凝胶的研制

目的：制备复方替硝唑凝胶，研究其质量控制，体外溶出试验及稳定性考察，为临床提供一种治疗牙周病局部给药新制剂。方法：采用多组分紫外分光光度法分别测定复方替硝唑凝胶中各药的含量，进行体外溶出试验、稳定性试验。结果：复方替硝唑凝胶制备容易，用二阶导数光谱法测定交沙霉素含量，可排除替硝唑和凝胶基质的干扰，并用紫外分光光度法直接测定替硝唑的含量。体外溶出试验表明复方替硝唑凝胶有缓释作用，释药时间较长稳定性试验表明复方替硝唑凝胶质量稳定，临床治疗牙周病总有效率为９７．４％。结论：本制剂制备容易，质量稳定，检测方法可靠，口内持药时间长，可作为临床治疗牙周病的一种剂型     

阿昔洛韦凝胶的研制与质量标准

目的研制阿昔洛韦凝胶.方法用卡波姆-940作凝胶基质,制备阿昔洛韦凝胶,建立酸碱度、卫生学、含量测定等质控方法,进行刺激性试验,光照试验,高速离心试验,耐热耐寒试验和自然室温留样考察.结果pH值6.5～7.0,卫生学检查符合规定,含量测定平均回收率100.2%～100.4%,RSD＜0.75%(n=5),且凝胶稳定无变化,无刺激性.结论制备该凝胶工艺简单,所得制剂质量可控,性质稳定,可满足临床用药需求.     

替硝唑凝胶剂的稳定性研究

采用HPLC法测定制剂含量,对替硝唑凝胶剂进行了温度、湿度,光加速进行了试验HPLC法测定制剂含量的平均回收率为101．6％．RSD为0．96％．根据Arrhenius方程推算替硝唑凝胶剂的室温贮存期为2．21年。试验表明：HPLC法测定替硝唑凝胶剂快速、准确、回收率高。在无强光直射务件下室温贮存本制剂较稳定,     

紫外分光光度法测定替硝唑膜剂的含量

建立替硝唑膜剂的含量测定方法。方法：采用紫外分光光度法测定膜剂中替硝唑的含量,以３１７ｎｍ为测定波长。结果：替硝唑浓度在５．０～２５．０μｇ·ｍｌ－１范围内与吸收度呈线性关系（ｒ＝０．９９９９）,平均回收率为１００．５％,ＲＳＤ为０．８％。结论：该法简便,准确,制剂中的其它成份不干扰测定。     

酮康唑酊剂的制备与质控研究

目的：为满足临床需要而研制的一种抗真菌制剂。方法：将酮康唑制剂成酊剂,建立了酸碱度、卫生学、含量测定等质控方法,并进行了刺激性和稳定性方面考察。结果：pH值为7．1－7．3,卫生学检查符合规定,含量测定平均回收率为100．52％,RSD＝0．81％,刺激性较小,稳定性较好。结论：本制剂制备工艺简便,质控方法准确可靠,性质稳定,适合临床应用。     

双氯芬酸凝胶的研究

以新型辅料Ｃａｒｂｏｐｏｌ－９４０制备了双氯芬酸凝胶剂，用高效液相色谱法测定双氯芬酸的含量，方法简便可靠。用恒温加速试验考察了该制剂的稳定性，有效期约２．６年。２４ｈ内累积透皮吸收百分率为５７．０％，对皮肤无刺激性。     

褶合光谱法测定复方替硝唑含漱剂含量

目的：研究测定复方替硝唑含漱剂含量的方法,方法：采用褶合光谱法不经分离直接测定替硝唑和醋酸氯己定的含量。结果：平均回收率和ＲＳＤ分别为９９．９５％,０．７４％,９９．９３％,０．５５％,结论：采用褶合光谱法不经分离直接测定复方中的两组分含量,方法简便,快速,结果准确。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.