This paper overviews the latest information on the impact of global warming on water cycles and resources, with a focus on links to health science. Many people may think that water issues mainly involve securing safe drinking water for regions lacking this crucial resource. However, of world water withdrawals, 70% is for agricultural water. Therefore, issues of water scarcity are highly connected with agriculture and food production. Global warming is expected to result in decreased water availability in semi-arid regions where major crop regions are located. Crop production in semi-arid regions already requires more water inputs than does agriculture in regions of ample natural rainfall; with global warming, the water situation in semi-arid regions is expected to worsen. In addition to the decrease in water for agriculture, domestic and drinking water supplies will also be threatened in semi-arid areas. In contrast, other regions may face the problem of too much water and flood disasters. Currently, the flood-affected population worldwide ranges from an annual minimum of approximately 30 million to a maximum of 300 million people. Projections for the late 21st century, however, suggest that 300 million will be the minimum number affected by flooding each year. The consequences of water decreases in some areas and increases in others caused by global warming will likely have close links to health. Therefore, health scientists should pay close attention to issues of climate and water resource change.

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Global warming is an unequivocal phenomenon today. Climate change including global warming has various effects on human health. The direct effects include increase in cases of heat-stroke and in mortality rate among those who have cardiovascular and and/or respiratory diseases. The main indirect effects are on infectious diseases. Vector-borne and water-borne infectious diseases are two main categories of infectious diseases that are forecasted to be most affected. There will be an increase in the number of vector-borne infections via expansion of the arthropod-infested areas, and increase in feeding behavior of infected mosquitoes. There will be increase in the number of cases with water-borne diarrhea diseases. It should, however, be noted that the levels of the impacts of climate change on human health will differ among regions, depending on factors such as social infrastructures, foreign trade and trip, age distribution, etc. Thus, the effects on health should be elucidated for each of the regions of the world. The studies of the effect of climate change on human health have been progressed in recent years; however, current understanding of the effect of climate change on human health including infectious diseases is not sufficient. Further studies are needed to understand in detail the effect of climate change on human health.

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The East Asia countries including Japan, China, Korea and Russia have been undergoing a rapid increase of economic and industrial development. However, large amounts of pollutants are released into the air and water. The main energy source, economic stage and lifestale are different in the above four countries and these differences cause the current diverse situation of atmospheric and water pollution in East Asia. This view describes the present stage of atmospheric pollution and countermeasures in East Asia including the author's recent research results concerning polycyclic aromatic hydrocarbons and nitropolycyclic aromatic hydrocarbons.

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Exposure to chemical warfare agents (CWAs) can be verified by detecting their degradation products in biological samples. However, the half-lives of these CWA degradation products in the body are short. CWAs are known to combine with biological macromolecules and the covalently bound compounds are called adducts. The residence time of adducts in the human body is longer than that of the corresponding CWA degradation products. Therefore, development of analytical methods to detect these adducts is a more realistic way of verifying CWA exposure. In this mini review, we describe the present state of research on analytical methods for identifying CWA adducts, and mainly introduce our research on nerve gas adducts using a direct method. Novel analytical methods for verifying low level exposure to nerve gases use liquid chromatography-mass spectrometry (LC-MS). Butyrylcholinesterase (BuChE) has been purified by affinity chromatography and sodium dodecylsulfate poly-acrylamide gel electrophoresis. The purified enzyme is inhibited by nerve gases (sarin, VX and soman) and digested by chymotrypsin, and then the peptides are analyzed by LC-MS and LC tandem MS. The peptide fragment that is combined with nerve gas is detected by LC-MS. Furthermore, the chemical structure of the adduct peptide characterized by MS provides structural information about the analyte. The detection limit of BuChE or BuChE adduct is estimated at 4 ng/injection (53 fmol/injection). If at least 1% of BuChE activity is inhibited by nerve gas, the adduct can be detected at a level of 1% BuChE inhibition in the victim's serum.

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Polycyclic aromatic hydrocarbon quinones (PAHQs) produced by combustion of gasoline exhibit two chemical characteristics; one is their electron transfer abilitiy, transferring electrons from reducing agents to molecular oxygen to generate reactive oxygen species (ROS) associated with oxidative stress and the other is their ability to arylate cellular proteins, resulting in the disruption of signal transduction pathways. This review summarizes toxicological and pharmacological significances of such envirnmental chemicals through redox cycling and covalent modification.

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The aim of our study was to demonstrate the suitability of urinary cotinine and plasma thiocyanates (SCN^-) as indicators of tobacco smoking and to investigate the correlation among urinary cotinine, plasma and urine SCN^- and number of cigarettes smoked per day and smoking topography. The initial study was conducted with 256 individuals: 143 nonsmokers aged 44.20±15.81 years and 113 current smokers aged 38.02±17.49 years. Subjects were classified into smokers or nonsmokers based on a questionnaire. Cotinine levels were measured using the enzymatic colorimetric method and SCN^- using selective electrodes. Urinary cotinine and plasma SCN^- levels are both significantly higher in smokers than in nonsmokers and correlate well with the number of cigarettes smoked per day. Urinary cotinine was significantly correlated with duration of consumption (F_3-109=3.43; p=0.019; r=0.9961), and there was a negative correlation between body mass index and urinary cotinine (r=0.9989, p<0.05). Urinary cotinine and plasma SCN^- levels discriminate between smokers and nonsmokers and increase when smoking exceeds 20 cigarettes/day and duration of consumption exceeds 5 years.

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Polychlorinated biphenyls (PCBs) are synthetic organic compounds with two phenyl groups well known environmental pollutants. This study examined the effect of persistent exposure to 2,3',4,4',5-pentachlorobiphenyl (PCB118) on serum cholesterol levels in male rats. Male Sprague Dawley rats were administered weekly intraperitoneal injections of either PCB118 (20 mg/kg) dissolved in corn oil or corn oil alone. One week after 2 and 5 administrations, the rats were sacrificed by a pentobarbital injection, and the effect of PCB118 on the serum levels of total cholesterol, high density lipoprotein-cholesterol (HDL-cholesterol), and low density lipoprotein-cholesterol (LDL-cholesterol) was investigated. The protein expression level of apolipoprotein A-I (apo A-I) and 3-hydroxy-3-methylgulutaryl coenzyme A (HMG-CoA) reductase was also examined. In this study, the administration of PCB118 induced hyperalphacholesterolemia in rats. In addition, the protein expression level of HMG-CoA reductase and apo A-I was higher in the PCB118-treated rats than in the control. These results suggest that the hyperalphacholesterolemia induced by PCB118 in male rats may be associated with an increase in HMG-CoA reductase and apo A-I expression.

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Our previous studies demonstrated that topic application of recombinant human acid fibroblast growth factor (aFGF) significantly, but still not completely, improved in diabetic ulcer healing. To obtain a maximal therapy for diabetic ulcer healing, a combined protocol containing aFGF, anti-oxidative reagent zinc (Zn) and stem cell stimulator granulocyte colony-stimulating factor (G-CSF), i.e.: aFGF/G-CSF/zinc sulphate (ZnSO₄), was explored in the present study. Diabetes was induced by a single dose of streptozotocin (STZ, 55 mg/kg) in Sprague Dawley rats, and full thickness skin wound was made in diabetic rats at 2 months after diabetes onset. Diabetic ulcer rats were treated with aFGF, G-CSF, ZnSO₄, aFGF/G-CSF/ZnSO₄ or vehicle control, respectively and 3, 6, 9, 12, 15, 18, 21 and 28 days later, therapeutic effects were evaluated by calculating ulcer area. On day 7, 14, 21 after treatment, rats were sacrificed to collect 2 pieces of dorsal skin from 3 different sites (wound center, edge and healed area) to perform histopathological examination. Results showed that treatment with aFGF/G-CSF/ZnSO₄ significantly enhanced ulcer healing compared with single drug treatment groups at different time points. Healing times for 100% of the wound in the aFGF/G-CSF/ZnSO₄ group was 20.00±1.15 days, and significantly shorter than those in single treatment groups (p<0.05). Histopathological and immunohistochemical analysis disclosed significant increases in capillary density, proliferating cells, the expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) and the ratios of TIMP-1 to matrix metalloproteinase 1 (MMP-1) in aFGF/G-CSF/ZnSO₄ group as compared to other single treatments. Collectively, the combinative protocol of aFGF/G-CSF/ZnSO₄ significantly enhanced the therapeutic effect on diabetic ulcer wound, probably through the promotion of fibroblast proliferation and differentiation, enhancement of blood vessel regeneration, and up-regulation of TIMP-1 and down-regulation of MMP-1 expression in diabetic ulcer healing process.

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In our current study, we investigated the expression profiles of the cytochromes P450 (CYPs) and transporters of the ocular tissues in Sprague-Dawley (SD) rats. Extensive expression of CYP1A1 in the cornea and CYP2E1 in the iris was observed whereas the expression of CYP2B1 and transporters was mostly ubiquitous throughout the ocular tissues. To further understand the regulation of these genes in ocular tissues, we investigated the effects of CYP inducers on the expression of the CYP and other xenobiotic-metabolizing enzyme genes in the cornea and lens. The administration of β-naphthoflavone (BNF), an agonist for aryl hydrocarbon receptor (AhR), induced CYP1A1 gene expression in the cornea, lens and liver of the rats, although the levels of induction were greatest in the liver. An AhR-sensitive UDP-glucuronosyl transferase (UGT) 1A6 gene was also induced in the cornea and the lens by BNF. Phenobarbital (PB) is a known inducer of the CYP2B genes, the expression of which is mediated by constitutive activated receptor (CAR), but did not induce CYP2B1 in the cornea or lens. This insensitivity to PB may be due to the lack of CAR expression in the ocular tissues as revealed in our present study. Pregnenolone-16α-carbonitrile (PCN) is known to induce CYP3A gene expression in the liver via the activation of pregnane X receptor (PXR). However, although PCN was found to induce the CYP3A1 gene in the rat cornea and liver, it failed to do so in the lens. In addition, another of the PXR-mediated genes, multidrug resistance-associated protein 3 (Mrp3), was not induced by PCN in either ocular region. Since the expression of the PXR gene was not detected in the rat ocular tissues, an unknown mechanism for the inducible regulation of CYP3A1 gene expression by PCN in the cornea is suggested.

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Vitellogenin (VTG) is a useful biomarker for detecting the estrogenic activity of chemicals in aquatic environments. However, little information is available on the regulatory mechanisms of the expression of each VTG subtype, particularly the relationship between expression patterns of VTG1/2 and estrogen receptor (ER) subtypes, such as ERα and ERβ. In this paper, we measured VTG1 and VTG2 mRNA induction in male medaka liver, which was treated with ERα-selective ligand, (17α, 20E)-3-hydroxy-17,20-[(1-methoxyethylidene)bis(oxy)]-19-norpregna-1,3,5(10),20-tetraene-21-carboxylic acid, methyl ester or ERβ-selective ligand, 2-(4-hydroxyphenyl)-5-hydroxy-1,3-benzoxazole and investigated the characteristics of ER subtype function in VTG1 and VTG2 inductions. Hepatic VTG1 mRNA was induced by ERα-selective ligands at even low concentration and maximum increases were the same as for E2. VTG2 mRNA was also increased, but its levels were very low. On the other hand, ERβ-selective ligands significantly increased VTG2 mRNA in the presence of ERα agonists. These results indicate that the expression of each VTG subtype is regulated by unique ER subtypes. VTG1 expression is only regulated by the action of ERα. In contrast, VTG2 expression is regulated by both ERα and ERβ, with ERα being essential for VTG2 gene expression and ERβ being essential for enhancement.

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Solid phase-supported receptor and ligand competitive assays for biotin were tested with respect to a mathematical model. We could assume the same mathematical model for both the solid phase-supported receptor and ligand competitive assays. In addition, we could eliminate the so-called blocking procedure in these assays. The amount of immobilizing reagent (biotinylated bovine serum albumin, BBSA) in the solid phase-supported ligand competitive assay was less than that (avidin) in the solid phase-supported receptor competitive assay. Desthiobiotin and biocytin influenced the solid phase-supported ligand competitive assay, but lipoic acid and lysine did not.

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Chronically, sun-exposed human skin is characterized by dermal connective tissue damage with the accumulation of abnormal elastic fibers. However, little is known about the relationship between accumulation of abnormal elastic fibers and photodamaged skin. In the present study, we investigated the involvement of reactive oxygen species (ROS) in photoaged skin including abnormal accumulation of tropoelastin (TE) induced by ultraviolet A (UVA)-irradiation using an in vitro model of elastic fiber formation. Our data showed that the morphological appearances of TE deposition was observed following the addition of recombinant TE immediately after treatment with UVA-irradiation by immunofluorescence staining and semi-quantitative assay. Our data also revealed that treatment with hypoxanthine-xanthine oxidase, which generates superoxide radicals, stimulated TE deposition. Furthermore, we confirmed that abnormal TE deposition induced by UVA-irradiation was inhibited by treatment with Cu/Zn superoxide dismutase, a superoxide radical scavenger. Therefore, the data obtained suggest that superoxide radical is a candidate for inducing morphological changes and increasing TE deposition induced by UVA-irradiation in human skin fibroblast cells. The present study would be helpful for developing a prophylactic agent for photoaged skin.

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Cadmium salts induce severe acute testicular necrosis in rodents. We assessed the expression levels of the genes encoding the follicle-stimulating hormone receptor, luteinizing hormone receptor, testis-specific histone 2B, and transition proteins 1 and 2, which are preferentially expressed in Sertoli cells, Leydig cells, spermatocytes, and spermatids, respectively, by reverse transcription (RT)-PCR using total RNA prepared from the whole testes of cadmium chloride (Cd)-administered rats. Spraque Dawley rats at 3, 7, and 12 weeks of age were singly and subcutaneously injected with Cd at doses of 1, 2.5, 5, 10, 15 or 20 μmol/kg. The expression levels of all genes tested were significantly decreased at doses of over 15 μmol/kg (3-week-old rats) or over 10 μmol/kg (7- and 12-week-old rats) 96 hr after injection. Histopathological study showed that these dosages of Cd resulted in extensive disruption of the seminiferous tubules and necrosis of testicular cells, while administration of Cd at a dose of 5 μmol/kg in 7- and 12-week-old rats resulted in only partial degeneration of seminiferous tubules and testicular cells. Therefore, their reduced gene expression is likely to serve as an indicator of Cd-induced testicular necrosis accompanied by cell death. In addition, the susceptibility to Cd-induced testicular damage and decreased gene expression was higher in mature (7- and 12-week-old) rats than in immature (3-week-old) rats.

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Authors' Comments:

We deeply regret that part of the experimental data we previously published in the Korean Journal of Physiology and Pharmacology, 8, 173-179, August (2004) was included in the above-mentioned article by mistake.
Therefore, we would like to withdraw this article written by Dao Kyong Kim, Yong Koo Kang, Moo Yeol Lee, Kwang-Gill Lee, Joo-Hong Yeo, Won Bok Lee, Yong Sik Kim, and Sung Su Kim from the Journal of Health Science.

Sung Su Kim
Department of Anatomy, College of Medicine, Chung-Ang University, Korea

September 15, 2009

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