Oxidative stress is a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species (ROS) in cells and tissues and the ability of a biological system to detoxify these reactive products. ROS can play, and in fact they do it, several physiological roles (i.e., cell signaling), and they are normally generated as by-products of oxygen metabolism; despite this, environmental stressors (i.e., UV, ionizing radiations, pollutants, and heavy metals) and xenobiotics (i.e., antiblastic drugs) contribute to greatly increase ROS production, therefore causing the imbalance that leads to cell and tissue damage (oxidative stress). Several antioxidants have been exploited in recent years for their actual or supposed beneficial effect against oxidative stress, such as vitamin E, flavonoids, and polyphenols. While we tend to describe oxidative stress just as harmful for human body, it is true as well that it is exploited as a therapeutic approach to treat clinical conditions such as cancer, with a certain degree of clinical success. In this review, we will describe the most recent findings in the oxidative stress field, highlighting both its bad and good sides for human health.

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Oxidative Stress: Harms and Benefits for Human Health

MEDICAL LITERATURE has been deluged during the past few years with books and papers on penicillin; but a book which has been produced under the general editorship of Sir Alexander Fleming himself represents a complete and authoritative summary of penicillin therapy as it stands today.' The book contains a series of independent contributions by \"experienced and eminent men who have worked with penicillin in Great Britain\". Their opinions and practical methods differ slightly, and there is some overlapping; but these are not disadvantageous, comparison and contrast lending interest to the reading. In the first or general section of the book Fleming contributes two chapters, one on the history and development of penicillin, introducing some interesting sidelights in the romance of discovery, the other on the bacteriological control of penicillin therapy. In both chapters the information is set out in meticulous detail and with a clarity and simplicity which can be enjoyed by all readers. Fleming also gives the right perspective to the place of penicillin amongst the antibiotics and lays down the principles of treatment. Both chapters are well illustrated and are the most outstanding in the book. Included in this first section also are chapters on the chemistry and manufacture of penicillin and its pharmacy, pharmacology and methods of administration. The second section of the book is entirely clinical, giving each author's view on the use of penicillin therapy in a disease or an infection of some particular region of the body. The entire range of peniCillin-sensitive conditions is considered in twenty authoritative and clearly written chapters; these contain many references and illustrations. Dental and veterinary diseases are also given fairly full consideration. The final section is a condensed resume of much of the preceding chapters and is written for. the general practttioner. This chapter is superttuous: it does not contain enough detall to be of much practical value. The book as a Whole, however, will undoubtedly be considered a classical contribution to medical literature and is strongly recommended, not only because of the general interest of its topic, but as a reference book on penicillin therapy of hitherto unequalled excellence. The typography, although conforming to war economy standards, is clear and the paper is good. There is an excellent list of references and the index is satisfactory.

Gray's Anatomy

Curcumin is the active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa). Curcumin has a surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. The pleiotropic activities of curcumin derive from its complex chemistry as well as its ability to influence multiple signaling pathways, including survival pathways such as those regulated by NF-κB, Akt, and growth factors; cytoprotective pathways dependent on Nrf2; and metastatic and angiogenic pathways. Curcumin is a free radical scavenger and hydrogen donor, and exhibits both pro- and antioxidant activity. It also binds metals, particularly iron and copper, and can function as an iron chelator. Curcumin is remarkably non-toxic and exhibits limited bioavailability. Curcumin exhibits great promise as a therapeutic agent, and is currently in human clinical trials for a variety of conditions, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis and Alzheimer’s disease.

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Curcumin: From ancient medicine to current clinical trials

Turmeric, derived from the plant Curcuma longa, is a gold-colored spice commonly used in the Indian subcontinent, not only for health care but also for the preservation of food and as a yellow dye for textiles. Curcumin, which gives the yellow color to turmeric, was first isolated almost two centuries ago, and its structure as diferuloylmethane was determined in 1910. Since the time of Ayurveda (1900 Bc) numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders. Extensive research within the last half century has proven that most of these activities, once associated with turmeric, are due to curcumin. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer's disease, and other chronic illnesses. These effects are mediated through the regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other enzymes. Curcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e.g., HUMIRA, REMICADE, and ENBREL), a vascular endothelial cell growth factor blocker (e.g., AVASTIN), human epidermal growth factor receptor blockers (e.g., ERBITUX, ERLOTINIB, and GEFTINIB), and a HER2 blocker (e.g., HERCEPTIN). Considering the recent scientific bandwagon that multitargeted therapy is better than monotargeted therapy for most diseases, curcumin can be considered an ideal "Spice for Life".

Curcumin: The Indian solid gold

Textbook of histology

MAJOR SALIVARY GLANDS OF BOTH HUMANS AND RODENTS CONSIST OF THREE PAIRS OF MACROSCOPIC GLANDS: parotid, submandibular, and sublingual. These glands secrete serous, mucous or mixed saliva via the proper main excretory ducts connecting the glandular bodies with the oral cavity. A series of discoveries about the salivary ducts in the 17th century by Niels Stensen (1638-1686), Thomas Wharton (1614-1673), and Caspar Bartholin (1655-1738) established the concept of exocrine secretion as well as salivary glands. Recent investigations have revealed the endocrine functions of parotin and a variety of cell growth factors produced by salivary glands.The present review aims to describe macroscopic findings on the major salivary glands of rodents and the microscopic differences between those of humans and rodents, which review should be of interest to those researchers studying salivary glands.

Anatomy and Histology of Rodent and Human Major Salivary Glands: —Overview of the Japan Salivary Gland Society-Sponsored Workshop—

A variety of beta-diketones were evaluated for their cytotoxic profiles against oral human normal and tumor cells. Among 22 compounds (BD1-22) tested, the cytotoxicity of 3-formylchromone (BD17) (CC50=7.8 microg/mL) against human oral squamous cell carcinoma (HSC-2) cells was higher than that of curcumin (CC50=23.6 microg/mL). Tumor cell-specific cytotoxicity was also detected in BD17 which exhibited little cytotoxic activity against a normal human cell, gingival fibroblast (HGF). (-)-3- (BD13) (CC50=21.7 microg/mL) and (+)-3-(Trifluoroacetyl)camphor (BD12) (CC50=29.7 microg/mL) are enantiomers and showed cytotoxicity comparable to curcumin and dibenzoylmethane (BD2) (CC50=22.5 microg/mL). BD13 did not induce DNA fragmentation in HL-60 cells nor activate caspase 3, 8 and 9 in both HL-60 and HSC-2 cells, regardless of the presence or absence of FeCl3. On the other hand, BD17 was found to induce apoptosis in HSC-2 and HL-60 cells, as judged by internucleosomal DNA fragmentation, caspase 3, 8 and 9 activation and dysfunction of mitochondrial membrane potential. The cytotoxic activity of BD13, BD17 and curcumin was significantly reduced by chelation with FeCl3. The tumor-specific cytotoxicity and apoptosis-inducing activity of BD17 against human tumor cells undoubtedly warrant further studies of its efficacy as a cancer chemotherapeutic agent.

Induction of apoptosis by beta-diketones in human tumor cells.

Fluoride has been used to prevent caries in the dentition, but the possible underlying mechanisms of cytotoxicity induction by this compound are still unclear. Since fluoride is known as an inhibitor of glycolytic enzymes, we investigated the possible connection between NaF-induced apoptosis and glycolysis in human promyelocytic leukemia HL-60 cells. NaF-induced apoptotic cell death is characterized by caspase activation, internucleosomal DNA fragmentation, loss of mitochondrial membrane potential, and production of apoptotic bodies. Higher activation of caspases-3 and -9, as compared with that of caspase-8, suggested the involvement of an extrinsic pathway. Utilization of glucose was nearly halted by NaF, whereas that of glutamine was rather enhanced. NaF enhanced the expression of Bad protein, but not that of Bcl-2 and Bax proteins, and reduced HIF-1 mRNA expression. Analysis of these data suggests a possible link between glycolysis and apoptosis.

Possible link between glycolysis and apoptosis induced by sodium fluoride

Background/Aim: We have previously reported that doxorubicin (DXR) showed much higher cytotoxicity against human oral squamous cell carcinoma cell lines compared to normal human mesenchymal normal oral cells (gingival fibroblast, periodontal ligament fibroblast, pulp cell), yielding high tumor-specificity. However, we unexpectedly found that doxorubicin showed potent cytotoxicity against human normal oral keratinocytes and primary gingival epithelial cells. In the present study, we investigated the reproducibility, underlining mechanisms and generality of this unexpected finding. Materials and Methods: Viable cell number was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, fine cell structure by transmission electron microscopy and apoptosis induction by western blot analysis. Results: Doxorubicin induced keratinocyte toxicity, regardless of cell density and concentration of FBS in the culture medium. Doxorubicin induced apoptosis (characterized by the loss of cell surface microvilli, chromatin condensation, nuclear fragmentation and caspase-3 activation) in keratinocytes. A total of 11 anticancer drugs showed similar keratinocyte toxicity. Alkaline extract of the leaves of Sasa senanensis Rehder partially alleviated the DXR-induced keratinocyte cytotoxicity by promoting cell growth. Conclusion: The present study suggested that oral keratinocyte toxicity is a novel adverse effect of most anticancer agents.

Induction of Apoptosis in Human Oral Keratinocyte by Doxorubicin.

Amino acid utilization of mouse macrophage-like RAW264.7 cells was investigated. During the logarithmic growth stage, RAW264.7 cells grew very fast, with an approximate doubling time of 11 hours, in DMEM supplemented with 10% heat-inactivated fetal bovine serum. RAW264.7 cells consumed glutamine at the fastest rate, followed by serine, leucine, isoleucine, arginine, lysine, valine and other amino acids. When the cell density reached a critical threshold level, cells began to suffer non-apoptotic cell death characterized by mitochondrial damage (revealed by transmission electron microscopy) and a smear pattern of DNA fragmentation (revealed by agarose gel electrophoresis). At this point, glutamine, serine and glucose in the medium were almost completely exhausted, whereas other amino acids remained at more than 40% of their initial concentrations. Based on these data, it is recommended that glutamine, serine and glucose should be supplemented for the long culture of RAW264.7 cells.

Osamu Amano

Papers

Anatomy and Histology of Rodent and Human Major Salivary Glands: —Overview of the Japan Salivary Gland Society-Sponsored Workshop—

Induction of apoptosis by beta-diketones in human tumor cells.

Possible link between glycolysis and apoptosis induced by sodium fluoride

Induction of Apoptosis in Human Oral Keratinocyte by Doxorubicin.

Cell Death Induced by Nutritional Starvation in Mouse Macrophage-like RAW264.7 Cells