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The investigation of angiogenesis in therapy is focused on two aspects, induction and inhibition of neovascularization. Proangiogeneinc effects are very essential in isochemic vascular disease, and increasing capillary density in isochemic muscle is important for blood supply to an entire target organ. Anti-angiogenic activity is desired in development of solid tumors. In this case an elimination of blood supply into developing cancer tissue may result in inhibiting of tumor growth. The development of anti-angiogenic agents is one of the major approaches in many laboratories around the world that are focused on investigation of new cancer therapy directions. The strategy of designing of new anti-angiogenesis agents is focused in three directions, (i) blocking of factors that stimulate angiogenesis, (ii) blocking of adhesion receptors presents on endothelial cells, (iii) blocking of proteolytic enzymes (MMPs) that degrade extracellular matrix during new vessel formation. Very interesting approaches have been developed by investigation of endogenous modulators of angiogenesis. The list of these molecules contains several molecules including, angiostatin, endostatin, tumbstatin, arrestein, kininogen, thrombospondin, and presumably the list will grow in the near future. Moreover, there were identified naturally occurring substances that affect the neovascularization process. Some of them like bacterial toxin (ZD0101), fungal protein (TNP-40), extract form dogfish shark liver (see review by Mousa) are in clinical trials. The review papers presented in this issue of the journal summarize directions that are currently being considered in pharmacological targeting of angiogenesis. The authors of these articles provide general overview of physiologically important elements of angiogenesis, and review most of the inhibitors and stimulators of the neovascularization process. The excellent summary of angiogenesis factors and inhibitors are provided by Mousa and Mousa [1]. The haemostatic system has been shown as an important paradigm in regulation of angiogenesis. The components of coagulation and fibrinolytic systems participate in this process. The activity of haemostatic enzymes affects several molecules modulating new vessel formation. Moreover, tissue factor as well as many anticoagulant drugs affect cancer development. The anti-angiogenic therapy is not only limited to tumor. This review also underlines a new approach to human ocular angiogenesis-mediated disorders such as diabetic retinopathy and age related macular degeneration, and to multiple myeloma that is characterized by increased levels of bone marrow vascularization. The perspectives in anti-angiogenic therapy of tumor are presented by Tortora and his colleagues [2]. He summarizes currently published stimulators and inhibitors of angiogenesis in the aspect of their potentials in clinical trials. The special attention of the authors is focused on the growth factors and their receptors. These molecules are critical for cell signaling, which is a crucial element of induction of proliferation and migration of endothelial cells during angiogenesis. The strategy for development of inhibitors of the signal transduction pathways in cells involved in neovascularization process is important direction for designing new therapeutics in cancer therapy. The general overview of inhibitors of angiogenesis that are currently in clinical trials is provided by Albo and Tuszynski [3]. The authors segregated angiostatic compounds regarding their mechanism of action on new blood vessels formation. The very interesting topics of this article include the discussion of the trials and tribulations of the use of antiangiostatic agents in patients with cancer. The practical application of these drugs including dosage and scheduling are still under intensive investigation. The idea of combination therapy of angiostatics with chemotherapeutics or radiation is also beautifully discussed in this review. Duffy [4] presented a general overview of urokinase plasminogen activator (uPA) system, which is involved in the multiple steps of cancer progression. The inhibition of uPA catalytic activity as well as prevention of uPA binding to its receptor significantly reduces tumor growth, angiogenesis and metastasis. The inhibitors of uPA activity are currently entering clinical trials, whereas uPAR antagonists are intensively investigated in animal models and are being considered for clinical trials. This review also discusses a role of elements of the uPA system as prognostic markers in certain types of tumors including breast cancer. The anti-angiogenic therapy is a new approach in treatment of patients with cancer. However, the clinical trials of new angiostatic compounds in many cases showed disparity with pre-clinical experimental findings. Most of the above reviews briefly describe these problems providing potential explanations of drug resistance in therapy. Ton and Jason [5] give an even a wider discussion of the lack of activity of certain angiostatic drugs in tumor treatment. Their discussion focuses on the inhibitors of VEGF its receptors. Although the neovascularization problem of blood vessels is widely discussed, the formation of new lymphatic vessels (lymphangiogenesis) is investigated in the lesser extent. The two last review articles discuss new directions in controlling of growth of lymphatic vessels. Stracker et al [6] provides a summary of molecules that are involved in biology of lymphatic vasculature. Dysfunction of lymphatic EC leads to many disorders including lymphodema, and metastatic spread of solid tumors. The investigation of these processes resulted in the preclinical trials of both pro-lymphangiogenic (lymphedema) and anti-lymphangiogenic approaches (tumor spreading). Besides discussing the current stage of biology of the lymphatic vasculature, Stracker and his colleagues outline future directions. They argue that the most promising pharmaceutical targets are lymphangiogenic growth factors and their dependent signaling pathways in lymphatic EC. Witling and Schweigerer [7] overview the panel of disorders caused by dysplasias of the lymphatic vessels. The potential directions that may result in reconstruction (engineering) of lymphatic capillaries are considered as a therapeutic strategy for different types of lymphedema. References [1] Mousa SA, Mousa AS. Angiogenesis Inhibitors: Current & Future Directions. Curr Pharm Design 2004; 10(1): 1-9. [2] Tortora G, Melisi D, Ciardiello F. Angiogenesis: A Target for Cancer Therapy. Curr Pharm Design 2004; 10(1): 11-26. [3] Albo D, Wang TN, Tuszynski GP. Antiangiogenic Therapy. Curr Pharm Design 2004; 10(1): 27-37. [4] Duffy MJ. The Urokinase Plasminogen Activator System: Role in Malignancy. Curr Pharm Design 2004; 10(1): 39-49. [5] Ton NC, Jayson GC. Resistance to Anti-VEGF Agents. Curr Pharm Design 2004; 10(1): 51-64. [6] Stacker SA, Hughes RA, Achen MG. Molecular Targeting of Lymphatics for Therapy. Curr Pharm Design 2004; 10(1): 65-74. [7] Wilting J, Schweigerer L. Development and Engineering of Lymphatic Endothelial Cells: Clinical Implications. Curr Pharm Design 2004; 10(1): 75-80.

The tropane alkaloid anisodamine (2) is obtained by 6β-hydroxylation of hyoscyamine (1). The application of this alkaloid in medicine is gaining attention due to the wide range of therapeutic applications described in addition to its anticholinergic activity. In this work, the production of anisodamine (2) by in vitro cultures of Brugmansia candida (Argentinean and Colombian samples) was studied. This alkaloid was estimated in different organs of in vitro-germinated seedlings as well as in hairy roots obtained from seedlings from both sources. Colombian roots exhibited the highest content of tropane alkaloids, with anisodamine (2) being the main alkaloid measured. In the leaves, the main alkaloid was scopolamine (3) and no significant differences were observed between Argentinean and Colombian leaves. The tropane alkaloid content in Argentinean hairy roots was significantly higher than in Colombian ones. Also, in the Argentinean samples the main alkaloid detected was anisodamine (2). Argentinean and Colombian B. candida seedlings and hairy roots appear to be a promising system for the production of anisodamine (2). [ABSTRACT FROM AUTHOR]

Byline: Yong-wei. Li, Chun-xia. Wang, Jian-she. Chen, Lu. Chen, Xiao-qian. Zhang, Yue. Hu, Xiao-bin. Niu, Dong-xu. Pei, Xin-wei. Liu, Yong-yi. BiPurpose: An association between catechol-O-methyltransferase (COMT) 158G/A polymorphism and endometriosis/adenomyosis [...]

The authors investigated the impact of effluents from a car battery manufacturing plant in Nnewi, Nigeria, on water, soil, and food qualities. The authors analyzed heavy metals mercury, arsenic, lead, cadmium and nickel in tap and cassava waters, soil, dried cassava tuber, and edible fruit samples from the company, using an atomic absorption spectrophotometer. Other parameters the authors analyzed include pH, electrical conductivity (EC), salinity (SAL), total hardness (TH), biological oxygen demand (BOD), volatile and nonvolatile solids, and bacterial and fungal loads of the soil samples. Results show that lead had the highest concentration in all the samples, with the soil samples having the highest lead concentration (38-12 ppm, 102 ppm) and the water samples having the lowest (0.02-0.20 ppm). Mercury had the lowest concentration (, CONTAMINANTS OF THE ENVIRONMENT include those arising from agricultural activities, gaseous deposits from the air, industrial effluents, wastewater sewage, and air particulates. (1) Waste materials may be released into the [...]

Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also [...]

To the editor.--'Arsenic Body Burden and Morbidity and Mortality.' The U.S. Environmental Protection Agency (EPA) is under Congressional mandate to lower the maximum contaminant level for arsenic in drinking water.[1] [...]