Melatonin and clinical application.

A review of the different publications dealing with melatonin in humans shows that this field has been very active in the last few years. Normative melatonin values have been defined. Various relationships between melatonin and other traits have been studied, such as sleep, circadian rhythm, surgical stress and anaesthesia. Age-related melatonin studies and melatonin during depression and other psychiatric disorders have been reviewed. Finally, some studies have been performed to use melatonin as a medication for sleep disturbance in depression, for jet-lag and as a skin protector for ultraviolet light.     

Molecular cloning of HCV and clinical application

Abstract: Fifty-five clones encoding epitopes of HCV were isolated from Japanese patients. Their amino acid homology (AAH) to the sequence of prototype (HCV-1) ranged from 47% to 94%. These sequences cover 60% of the HCV genome lacking M/E and NS2 regions suggesting a very low or lacking immunogenecity for these regions. Two test kits for detection of anti-HCV antibody were developed using a combination of a synthetic peptide (AR142) containing the epitope of N14 (QRKTKRSTNRR) having a homology to the core of HCV of | fr | sol 8/11AA and a non-fusion recombinant protein Y19 starting from amino acid number (AAN) 1380 to 1507 in the NS3 region showing a AAH to the HCV-1 of 90%, and a combination of a mixture of three synthetic peptides of S29 AAN of 1–30, 38–65 and 47–74 of the core and a non-fused recombinant protein S4 AAN of 1287–1506 having a 93% AAH of the NS3 region. They showed almost the same order of sensitivity and specificity of the second-generation kits when tested with serum from blood donors and patients with non-A, non-B hepatitis. It should also be stressed that in all of the complete responders of a recombinant α-interferon therapy, the antibody levels against AR142 gradually decreased during and after the treatment. In 1992, studies performed for 125 patients with hepatocellular carcinoma in our clinic shows that of these 16 patients might developed from either chronic non-B, non-C liver diseases or chronic liver diseases caused by mutant(s) of HCV as their serum were negative for HBsAg and second-generation of anti-HCV.     

Anticancer mechanisms and clinical application of alkylphospholipids

Synthetic alkylphospholipids (ALPs), such as edelfosine, miltefosine, perifosine, erucylphosphocholine and erufosine, represent a relatively new class of structurally related antitumor agents that act on cell membranes rather than on DNA. They selectively target proliferating (tumor) cells, inducing growth arrest and apoptosis, and are potent sensitizers of conventional chemo- and radiotherapy. ALPs easily insert in the outer leaflet of the plasma membrane and cross the membrane via an ATP-dependent CDC50a-containing ‘flippase’ complex (in carcinoma cells), or are internalized by lipid raft-dependent endocytosis (in lymphoma/leukemic cells). ALPs resist catabolic degradation, therefore accumulate in the cell and interfere with lipid-dependent survival signaling pathways, notably PI3K-Akt and Raf-Erk1/2, and de novo phospholipid biosynthesis. At the same time, stress pathways (e.g. stress-activated protein kinase/JNK) are activated to promote apoptosis. In many preclinical and clinical studies, perifosine was the most effective ALP, mainly because it inhibits Akt activity potently and consistently, also in vivo. This property is successfully exploited clinically in highly malignant tumors, such as multiple myeloma and neuroblastoma, in which a tyrosine kinase receptor/Akt pathway is amplified. In such cases, perifosine therapy is most effective in combination with conventional anticancer regimens or with rapamycin-type mTOR inhibitors, and may overcome resistance to these agents. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism.     

乳酸杆菌临床应用的研究进展

从乳酸杆菌及制剂类型、作用机制、应用研究、未来的发展前景等方面进行综述。     

氨甲蝶呤多聚谷氨酸的检测及其临床应用价值

氨甲蝶呤多聚谷氨酸（methotrexate polyglutamate,MTXPG）为氨甲蝶呤（methotrexate,MTX）在细胞内的代谢产物,其蓄积程度决定着MTX的细胞毒性和治疗效果。MTXPG的检测有利于监测其在细胞内的浓度,指导临床用药和预后判断。本文就MTXPG在细胞内的代谢过程、检测方法及其在临床疾病治疗中的应用价值做一综述。     

干细胞研究及其在临床医学上的应用

干细胞是一类具有自我更新和分化潜能的细胞,可以分为胚胎干细胞和成体干细胞两类。近来干细胞研究的二项重大技术突破：胚胎干细胞的体外培养和成体干细胞的横向分化,为干细胞在临床医学上的应用开辟了广阔的前景。     

七叶皂苷的药理作用与临床应用

娑罗子为七叶树科植物欧洲七叶树(Aesculus hippocastannum)、日本七叶树(Aesculus turbinata Blume)和中国天师栗(Aesculus Wilsonii Rehd)的果实或种子。欧洲七叶树,又名欧马栗(horse chestnut),其种子和幼枝的外皮可入药,在欧洲应用广泛,早在18世纪即用于解热,19世纪后期可用于治疗痔疮。七叶皂苷是从娑罗子(七叶树种子)中提取的主要活性成分,属于三萜皂苷类药物。它具有抗渗、消肿、改善血液循环、增加静脉张力、抑制胃排空、清除活性氧和抗肿瘤作用。临床上可广泛应用于慢性静脉功能不全,痔疮、水肿、哮喘等。本文对七叶皂苷的药理作用及其临床应用进行综述。     

猪胆汁注射液的制备与临床应用

胆汁有清热解毒、止咳平喘、消炎利胆、明目等功能,胆汁注射剂具有安全、有效、低毒的特点,有广泛的临床应用价值,介绍胆汁注射液的制备方法。     

Biology and clinical application of neural stem cells

Neural stem cells, which exist in various regions of the CNS throughout the mammalian lifespan, can be expanded and induced to differentiate into neurons and glia in vitro and in vivo. Because of these characteristics, there has been increasing interest in the identification and characterization of neural stem cells and neural progenitor cells both for basic developmental biology studies and for therapeutic applications to the damaged brain. Transplantation of neural stem cells or their derivatives into a host brain and the proliferation and differentiation of endogenous stem cells by pharmacological manipulations are potential treatments for many neurodegenerative diseases and brain injuries, such as Parkinson's disease, brain ischemia and spinal cord injury. Continued progress in neural stem cell research is providing a new future for brain repair.     

Advances in melanoma senescence and potential clinical application

Normal cells possess a limited proliferative life span, after which they enter a state of irreversible growth arrest, called replicative senescence, which acts as a potent barrier against transformation. Transformed cells have escaped the process of replicative senescence and theoretically can not re-enter senescence. However, recent observations showed that transformed cells, and particularly the melanoma cells, can still undergo oncogene or stress-induced senescence. This senescence state is accompanied by many of the markers associated with replicative senescence, such as flattened shape, increased acidic β-galactosidase activity, characteristic changes in gene expression and growth arrest. Interestingly, in some cancers, senescence induction following chemotherapy has been correlated with a favorable patient outcome. In this review, we gathered recent results describing senescence-like phenotype induction in melanoma cells and discuss why senescence may also be exploited as a therapeutic strategy in melanoma.     

Gastric tonometry and intramucosal pH--theoretical principles and clinical application

Gastric or intestinal luminal tonometry is a method for monitoring critically ill patients. It offers an index of the adequacy of aerobic metabolism in a tissue that is particularly sensitive to alterations in its perfusion and oxygenation: the gut mucosa. It is based on the measuring the increase in tissue CO2 production that accompanies anaerobic metabolism. The method simply consists of a balloon in the stomach, which measures intramucosal pCO2. From this measurement and from the arterial bicarbonate concentration gastric intramucosal pH (pHi) can be calculated, assuming that bicarbonate concentration in the gastric mucosal tissue is in equilibrium with systemic arterial bicarbonate. Despite possible clinical benefit from the measurement and the therapy of low pHi values in critically ill patients, the theoretical, experimental and pathophysiological implications for the monitoring of intramucosal acidosis in the gut are not yet fully understood. There are still some open methodological questions crucial for further clinical interpretation.     

Tumor-specific T-bodies: towards clinical application

 Unlike antibodies, T cells are well suited to penetrate and destroy solid tumors. The T-body approach combines antibody recognition and T cells effector function. It is based on T cells expressing chimeric receptors composed of antibody-derived Fv or scFv as their extracellular recognition elements joined to lymphocyte triggering molecules. This receptors can redirect the specificity of T cells in an MHC independent manner. Upon encountering their target cells, T-bodies are able to undergo specific stimulation for interleukin/cytokine production, and kill hapten-modified or tumor cells in model systems both in vitro and in vivo. T cells expressing chimeric receptors made of antitumor antibodies are able to discriminate between a tumor and normal cell with negligible bystander cytotoxicity. Further studies should be carried out to evaluate and optimize the persistence, homing patterns and reactivation potential of T-bodies in the body. Accepted: 14 October 1997     

Fibronectin assays and their clinical application: a review

Cold insoluble globulin (fibronectin) was discovered 30 years ago but recently there has been a remarkable growth of knowledge concerning its interaction with the cell cytoskeleton and its role in cell-cell and cell-matrix adhesion. The protein is also a major plasma opsonin with a role in regulating fixed macrophage activity and it is this area in which clinical applications are now beginning to develop. Methods are discussed for measuring the concentration of the protein and its opsonic function in vitro, and for the evaluation of fixed macrophage function in vivo. Also discussed are the metabolism of the protein, the implications of opsonin depletion in patients with serious injury or infection and the attempts to reverse this with plasma protein replacement therapy.