Inappropriate use of albino animals as models in research

Sensory-neural, biochemical-metabolic, and physiological anomalies occur in albino mammals. There are ontogenic and biochemical parallels between the senses, peripheral nervous system, endocrine glands, metabolism, and melanin pigmentation. All albino mammals examined have abnormal optic systems. Many drugs cannot be adequately evaluated in an albino model because of melanin's ability to bind and interact with some chemicals. There is evidence that a general reduction in melanin pigment is correlated with a paucity of amino acids necessary for normal chemical function of the brain. There is a high probability that enzyme levels indicative of metabolic performance are deficient in the liver and kidneys of albinos. Congenital defects are associated with hypopigmentation in animal models and human syndromes. Melanin is found in abundance in the eye, inner ear, and midbrain where neural impulses are initiated indicating a possible role as an electrophysiologic mechanism. Microwave irradiation differentially affects albino and pigmented animals. Implications of these observations and other reports of anomalies associated with hypopigmentation suggest caution in the use of albino and other hypomelanotic animals as normal models in biological research.     

The use of animal models in diabetes research

Diabetes is a disease characterized by a relative or absolute lack of insulin, leading to hyperglycaemia. There are two main types of diabetes: type 1 diabetes and type 2 diabetes. Type 1 diabetes is due to an autoimmune destruction of the insulin-producing pancreatic beta cells, and type 2 diabetes is caused by insulin resistance coupled by a failure of the beta cell to compensate. Animal models for type 1 diabetes range from animals with spontaneously developing autoimmune diabetes to chemical ablation of the pancreatic beta cells. Type 2 diabetes is modelled in both obese and non-obese animal models with varying degrees of insulin resistance and beta cell failure. This review outlines some of the models currently used in diabetes research. In addition, the use of transgenic and knock-out mouse models is discussed. Ideally, more than one animal model should be used to represent the diversity seen in human diabetic patients.     

The kidney as a target organ in pharmaceutical research

Kidney diseases are a major source of morbidity and mortality in humans. In developed countries, mortality owing to chronic kidney disease (CKD) terminating in end-stage renal failure is comparable with that associated with cancer. A full understanding of the mechanisms implicated in the progression of CKD is needed to achieve its prevention and to delay the need for support strategies based on dialysis and transplantation. Renal fibrosis is the unifying feature of progressive renal alterations. In this review, we discuss the current status of possible mechanisms, tools and targets in CKD. Pathophysiological compound identification, biomarker discovery and accurate selection of clinical validation criteria appear to be three key elements needed to develop a successful innovative pharmaceutical approach to treating kidney diseases.     

The use of quantum chemistry in pharmaceutical research as illustrated by case studies of indometacin and carbamazepine

A number of case studies that illustrate how quantum chemistry may be used in studying pharmaceutical systems are reviewed. A brief introduction to quantum methods is provided and the use of these methods in understanding the structure and properties of indometacin and carbamazepine is discussed. The use of calculated structures and molecular electrostatic potentials in developing quantitative structure-activity relationships is discussed along with the use of computation chemistry to predict spectroscopic properties.     

The use of N-methylpyrrolidone as a cosolvent and oxidant in pharmaceutical stress testing

The use of N-methylpyrrolidone (NMP) as an oxidant and cosolvent in pharmaceutical stress testing (forced degradation) is examined. Various active pharmaceutical ingredients were heated in NMP-water solutions under nitrogen, air, and oxygen and then analyzed by high-performance liquid chromatography, usually with ultraviolet diode array detection and mass spectrometry detection. In some cases, degradation products were isolated and characterized by nuclear magnetic resonance. The NMP-water-air-heat system provided oxidative and hydrolytic degradation products. The observed oxidation products were consistent with products expected from free radical autoxidation, reactions with hydroperoxides, and possibly singlet oxygen. Oxidative and hydrolytic pathways could be distinguished by comparison of the reactions carried out under air/oxygen and nitrogen. In many cases, the oxidation products observed during stress testing were also observed during formal stability studies of drug products. The NMP-water-air-heat stress condition facilitates various oxidative degradation pathways, which are often relevant to drug product on stability. This approach facilitates stability-indicating method development and helps elucidate degradation pathways.     

The use of in vitro cell culture models for mechanistic studies and as permeability screens for the blood-brain barrier in the pharmaceutical industry--background and current status in the drug discovery process

Successful drug delivery to the central nervous system (CNS) is highly dependent on DMPK as well as physicochemical properties and it is therefore important to characterise these properties and take them into account when designing chemical lead series that act at CNS targets. Since the drug discovery/development process is becoming increasingly focused on reducing the time required to enter molecules into the market, industrial DMPK scientists have emerged from their traditional supportive role in drug development to provide valuable support in the drug discovery process, using novel methods to meet the demands of combinatorial chemistry and bioscience groups.     

药学信息在药学科研中的应用

目的：介绍药学科研各环节中药学信息的应用，从而提高科研工作的效率与水平。方法：结合药学科研实际工作，介绍科研过程中药学信息的应用情况。结果：无论是在药学科研的选题与方案设计过程中，还是在药学科研方案的实施与总结过程中，药学科研人员都应快速、准确、全面地获取各种相关药学信息。结论：药学信息与药学科研工作息息相关。     

Purity as an issue in pharmaceutical research and development

In the third EUFEPS Nuremberg Conference, three important aspects in the purity area were extensively covered. The first one dealt with the setting up of practical strategies to establish specifications during the complete R&D process. An industrial strategy on how this goal could be reached was presented. A safety evaluation aspect reflecting the discussion between ten pharmaceutical companies was given and the regulatory point of view was presented. The second one focused on the physical aspect of the purity issue (polymorphism, crystallinity...). The scientific background of this problem was presented and the necessity to cover this problem during the early phases of an industrial R&D project was outlined. Regulatory aspects were covered and the necessity to perform in certain cases bioequivalence studies was pointed out. The last session raised the particularity of biotechnological products. The contributors stressed that the impurity limits should be based on safety evaluation as well as the necessity to review carefully the production methods. Finally, a review was done on the current progress of the ICH guidelines establishment.     

The use of fluorescent probes in pharmaceutical analysis

Even though many pharmaceuticals show native fluorescence, there is also an important group of compounds which is not fluorescent. A main object of studies is to make them fluorescent, principally by using fluorescent probes through derivatisation reactions. An account of the fluorescent probes more widely used for the determination of drugs and related compounds is presented in this review paper. A wide variety of fluorescent probes is described on the basis of their ability to react specifically with various functional groups. Attention is focused on derivatisation reactions used in spectrofluorimetry and chromatographic techniques (HPLC, TLC) with fluorimetric detection. The review covers only those fluorescent probes whose use involves a chemical reaction with the analyte, and not those methods that involve physico-chemical interactions such as sensitised or charge transfer processes.

Many of these derivatisation reactions have been widely used in the detection of primary and secondary amines. Reagents such as dansyl chloride, fluorescamine, o-phtalaldehyde are very well known. Other reagents have also been developed for other functional groups, for example dansyl hydrazine for compounds with a carbonyl function or 4-bromomethyl-7-methoxy-coumarin for acidic compounds . Acid chlorides such as dansyl chloride may also react with different functional groups carrying active hydrogens as do phenols.

The use and development of new fluorescent probes in pharmaceutical analysis is a subject for further studies.     

实验鱼类在药学研究中的应用

实验鱼类作为模式生物已经被广泛地应用于药学研究,其中犹以斑马鱼为经典。斑马鱼因其独特的优点,被建立人类重大疾病模型和药物筛选平台,取得了许多有价值的研究成果。另外,青鳝、虹鳟、剑尾鱼、稀有觞鲫、红鲫、金鱼、鲤鱼等实验鱼类也具有在药物开发与应用研究的优势。本文综述了近年来国内外实验鱼类在药物毒理学与安全性评价、环境化合物安全性评价、药物筛选与新药发现、药物药理学研究、药物代谢研究、药物制剂学研究、中药研究、再生药物研究等药学研究的一些事例,为药学研究中实验动物的选择积累有价值的资料,并为实验鱼类应用研究提供新的启示。     

The developing use of heterozygous mutant mouse models in brain monoamine transporter research

5-Hydroxytryptamine (5-HT), dopamine and norepinephrine are important monoamine neurotransmitters implicated in multiple brain mechanisms and regulated by high-affinity transmembrane monoamine transporters. Although knockout mice lacking 5-HT, dopamine or norepinephrine transporters are widely used to assess brain monoamine processes, these models have several methodological limitations. There is mounting evidence that heterozygous mutant mice with reduced (but not abolished) monoamine transporter functions could provide models with greater relevance to the genetics of human disorders, which only rarely involve complete loss-of-function mutations. Here, we discuss why heterozygous mouse models, in addition to knockout mice, might be useful for brain monoamine transporter research.     

临床药学实验研究在药学服务中的作用

药学服务(pharmaceutical care)的概念已经被引入国内多年,正成为本世纪我国医院药学发展的方向[1,2].临床药学工作被认为是药学服务的主体[3],而以实验手段解释临床用药中的有关问题则是临床药学重要的工作内容之一.临床药学实验研究的选题、目的、研究范围、实验手段及其在药学服务中的作用具有自身的特点,本文结合自身工作的体会及相关文献探讨如下.