Begell House Inc.
Journal of Environmental Pathology, Toxicology and Oncology
JEP(T)
0731-8898
29
2
2010
A Need for Reorganization of the Food and Drug Administration
81-84
10.1615/JEnvironPatholToxicolOncol.v29.i2.10
Richard
Edlich
Legacy Verified Level I Shock Trauma Center Pediatrics and Adults, Legacy Emanual Hospital; and Plastic Surgery, Biomedical Engineering and Emergency Medicine, University of Virginia Health System, USA
Shelley S.
Mason
Multiple Sclerosis Research Fund, Brush Prairie, WA, USA
Jill S.
Reddig
Multiple Sclerosis Research Fund, Brush Prairie, WA, USA
K. Dean
Gubler
Surgical Critical Care, Legacy Verified Level I Shock Trauma Center for Pediatrics and Adults, Legacy Emanuel Hospital, Portland, OR, USA
William B.
Long III
Trauma Specialists LLP, Legacy Verified Level I Shock Trauma Center for Pediatrics and Adults, Legacy Emmanuel Hospital, Portland, OR, USA
Food and Drug Administration
Center for Devices and Radiological Health
citizen’s petition
Grassley-Dodd bill
Government Accountability Office
Food and Drug Administration Safety Act of 2007
The associate director for science and medicine in the Office of Drug Safety at the Food and Drug Administration (FDA), Dr. David Graham, reported that the FDA was incapable of protecting Americans from unsafe drugs. In testimony to the Senate Finance Committee, he stated that the FDA has let the American people down and betrayed public trust. Drastic changes and measures within the FDA must be made to ensure the safety of American consumers of drugs, products, and medical devices. Efforts such as the introduction of the Grassley-Dodd Bill, allowing the FDA to order immediate drug recall or increased risk warnings, followed by the FDA Safety Act of 2007, are still not enough to ensure the safety and efficacy of drugs, biological products, and medical devices that the American public use every day. In this report, we describe past and present efforts by congressional leaders, FDA representatives, and American citizens to effect changes within the FDA in order to protect America from unsafe drugs and medical devices. We describe our own struggles in passing a citizen’s petition to ban cornstarch in medical gloves, and the lack of response and responsibility that the FDA has displayed.
Revolutionary Advances in the Diagnosis of Vitamin D Deficiency
85-89
10.1615/JEnvironPatholToxicolOncol.v29.i2.20
Richard
Edlich
Legacy Verified Level I Shock Trauma Center Pediatrics and Adults, Legacy Emanual Hospital; and Plastic Surgery, Biomedical Engineering and Emergency Medicine, University of Virginia Health System, USA
Shelley S.
Mason
Multiple Sclerosis Research Fund, Brush Prairie, WA, USA
Jill S.
Reddig
Multiple Sclerosis Research Fund, Brush Prairie, WA, USA
K. Dean
Gubler
Surgical Critical Care, Legacy Verified Level I Shock Trauma Center for Pediatrics and Adults, Legacy Emanuel Hospital, Portland, OR, USA
William B.
Long III
Trauma Specialists LLP, Legacy Verified Level I Shock Trauma Center for Pediatrics and Adults, Legacy Emmanuel Hospital, Portland, OR, USA
vitamin D deficiency
liquid chromotography tandem mass spectrometry
radioimmunoassay
immunochemiluminometrics
Vitamin D deficiency has bee associated with bone diseases, cardiovascular diseases, cancer, and multiple sclerosis. Recent clinical studies have pointed out that these diseases could be prevented by either adequate sun exposure or oral vitamin D3 supplementation. In an effort to prevent these illnesses, emergency physicians and other clinicians must be aware of technological advances in the measurement of serum concentrations of 25-hydroxyvitamin D. Realizing the importance of diagnosing vitamin D deficiency, we reviewed the following advanced diagnostic techniques: liquid chromatography tandem mass spectrometry, radioimmunoassay, and DiaSorin’s immunochemiluminometric automated analyzer LIASION®. On the basis of this review, we have found that each of these diagnostic tests has documented limitations, and therefore we recommend an international standardization of these assays to accurately diagnose vitamin D deficiency.
Protective Role of Zinc in Ameliorating Arsenic-Induced Oxidative Stress and Histological Changes in Rat Liver
91-100
10.1615/JEnvironPatholToxicolOncol.v29.i2.30
Ashok
Kumar
Department of Biophysics, Panjab University, Chandigarh, India
Anshoo
Malhotra
Department of Biophysics, PGIMER, Chandigarh India 160012
Praveen
Nair
Department of Biophysics, Panjab University, Chandigarh, India
M. L.
Garg
Department of Biophysics, Panjab University, Chandigarh, India
Devinder K.
Dhawan
Department of Biophysics and Centre of Nuclear Medicine, Institute for Emerging Areas in Science and Technology, Panjab University, Chandigarh, India
arsenic
liver
antioxidants
The aim of present work was to gain insight into the role of dietary zinc in ameliorating the adverse effects caused by arsenic on rat liver. Male Wistar rats received arsenic alone in the form of sodium arsenite in drinking water at a dose level of 100 ppm, zinc alone in the form of zinc sulfate in drinking water at a dose level of 227 mg/L, or arsenic + zinc treatments in the combined group for a total duration of 3 months. Arsenic treatment resulted in a significant increase in lipid peroxidase (LPO); however, glutathione (GSH) levels and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT) were found to be significantly decreased following arsenic treatment. Furthermore, arsenic treatment resulted in a significant decrease in hepatic zinc levels. Histological studies showed well-differentiated signs of focal hepatitis, lobular inflammation, prominent hepatocyte degeneration, and severe periportal necrosis. Administration of zinc to arsenic-treated rats significantly decreased the level of LPO but increased the level of GSH compared with arsenic-treated rats. Further, the zinc level and activities of SOD, GPx, GR, and CAT were found to be significantly increased following zinc treatment. The administration of zinc to arsenic-treated rats caused signs of improvement in liver histoarchitecture, but a few focal areas of degeneration and necrosis were still occasionally seen. In conclusion, the results of this study suggest that zinc can be beneficial against arsenic-induced hepatotoxicity in rats.
Protective Effect of Alstonia scholaris Against Radiation-Induced Clastogenic and Biochemical Alterations in Mice
101-111
10.1615/JEnvironPatholToxicolOncol.v29.i2.40
Swafiya
Jahan
Radiation and Cancer Biology Laboratory, Department of Zoology, University of Rajasthan, Jaipur, India
Pradeep Kumar
Goyal
Radiation and Cancer Biology Laboratory, Department of Zoology, University of Rajasthan, Jaipur - 302 004, India
gamma radiation
Alstonia scholaris
chromosomal aberrations
micronuclei
lipid peroxidation
glutathione
We studied the radioprotective effect of Alstonia scholaris bark extract (ASE) on cytogenetic alterations in the form of chromosomal aberrations and micronuclei induction in bone marrow. For this purpose, one group of male Swiss albino mice was exposed to 2.5 Gy gamma radiation to serve as the irradiated control, while the other group received ASE (100 mg/kg bwt/d) orally for 5 consecutive days 30 min before irradiation to serve as the experimental group. Results indicated that dicentrics and chromosomal exchanges were increased at 12 h post-exposure in both groups, followed by a gradual decline and then disappearance by d 15 and 7, respectively. However, the occurrence of chromatid breaks and acentric fragments was also maximum at 12 h, and later decreased without attaining the normal value, even up to the last necropsy interval. The percentage of such aberrations was significantly less in the ASE-pretreated irradiated animals. The incidence of chromosome breaks and centric rings kept increasing up to d 1, but then declined gradually and reached zero beginning at d 7; they were significantly lower in the ASE-treated irradiated group at the early intervals. A significant decrease in glutathione (GSH) and an increase in lipid peroxidation were observed after radiation exposure in untreated controls, whereas ASE-pretreated irradiated animals exhibited a significant increase in GSH and a decrease in lipid peroxidation; however, the values remained below normal. The results from the present study suggest that ASE pretreatment provides protection against radiation-induced chromosomal damage and micronuclei induction in the bone marrow of mice.
Diallyl Disulfide Induces Caspase-Dependent Apoptosis via Mitochondria-Mediated Intrinsic Pathway in B16F-10 Melanoma Cells by Up-Regulating P53, Caspase-3 and Down-Regulating Pro-Inflammatory Cytokines and Nuclear Factor- κβ-Mediated Bcl-2 Activation
113-125
10.1615/JEnvironPatholToxicolOncol.v29.i2.50
P.
Pratheeshkumar
Amala Cancer Research Centre, Amala Nagar, Thrissur-680555, Kerala State, India
P.
Thejass
Amala Cancer Research Centre, Amala Nagar, Thrissur-680555, Kerala State, India
Girija
Kuttan
Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala State, India
diallyl disulfide
apoptosis
B16F-10
NF-kB
p53
pro-inflammatory cytokines
Diallyl disulfide (DADS) is a major organo-sulfur compound derived from garlic (Allium sativum), which inhibits the proliferation of various types of cancer cells. In this study we investigated the effect of DADS on the induction of apoptosis, as well as its regulatory effect on the activation of transcription factors in B16F-10 melanoma cells. Treatment of B16F-10 cells with nontoxic concentrations of DADS resulted in the presence of apoptotic bodies and induced DNA fragmentation in a dose-dependent manner. Cell-cycle analysis revealed that the occurrence of the sub-G1 peak was significantly elevated in DADS-treated cells. DADS treatment also down-reguated Bcl-2 expression and up-regulated p53, caspase-9, and caspase-3 expression in B16F-10 melanoma cells. The study also reveals that DADS inhibited the activation and nuclear translocation of p65, p50, and c-Rel subunits of nuclear factor (NF)-ℵB and other transcription factors, such as c-fos, activated transcription factor-2, and cyclic adenosine monophosphate response element-binding protein, in B16F-10 melanoma cells The pro-inflammatory cytokine production and gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were down-regulated in DADS-treated cells compared with control B16F-10 metastatic melanoma cells. DADS induces caspase-dependent apoptosis through a mitochondria-mediated intrinsic pathway in B16F-10 melanoma cells by activating p53 and caspase-3 gene expression and suppressing pro-inflammatory cytokines and NF-ℵB-mediated Bcl-2 activation.
Anti-Tumor Activity of Aloe vera Against DMBA/Croton Oil-Induced Skin Papillomagenesis in Swiss Albino Mice
127-135
10.1615/JEnvironPatholToxicolOncol.v29.i2.60
M. R.
Saini
Radiation and Cancer Biology Laboratory, Department of Zoology, University of Rajasthan, Jaipur, India
Pradeep Kumar
Goyal
Radiation and Cancer Biology Laboratory, Department of Zoology, University of Rajasthan, Jaipur - 302 004, India
Geeta
Chaudhary
Radiation and Cancer Biology Laboratory, Department of Zoology, University of Rajasthan, Jaipur, India
chemical carcinogen
skin papilloma
chemoprevention
Aloe vera
Human populations are increasingly exposed to various carcinogens such as chemicals, radiation, and viruses in the environment. Chemopreventive drugs of plant origin are a promising strategy for cancer control because they are generally nontoxic or less toxic than synthetic che-mopreventive agents, and can be effective at different stages of carcinogenesis. The present investigation was undertaken to explore the antitumor activity of topical treatment with aloe vera (Aloe vera) gel, oral treatment with aloe vera extract, and topical and oral treatment with both gel and extract in stage-2 skin carcinogenesis in Swiss albino mice induced by 7,12-dim ethylbenz(a)anthracene (DMBA) and promoted croton (Croton tiglium) oil. The animals were randomly divided into 4 groups and treated as follows: Group I, DMBA + croton oil only (controls); Group II, DMBA + croton oil + topical aloe vera gel; Group III, DMBA + croton oil + oral aloe vera extract; Group I V, DMBA + croton oil + topical aloe vera gel + oral aloe vera extract. Results showed that body weight was significantly increased from 78.6% in the control group (Group I) to 92.5%, 87.5%, and 90.0% in Groups II, III, and I V, respectively. A 100% incidence of tumor development was noted in Group I, which was decreased to 50%, 60%, and 40% in Groups II, III, and I V, respectively. Also in Groups II, III, and IV, the cumulative number of papillomas was reduced significantly from 36 to 12, 15, and 11; tumor yield from 3.6 to 1.2, 1.5, and 1.1; and tumor burden from 3.6 to 2.4, 2.50, and 2.75, respectively, after treatment with aloe vera. Conversely, the average latent period increased significantly from 4.9 (Group I) to 5.23, 5.0, and 6.01 weeks in Groups II, III, and I V, respectively. We conclude that aloe vera protects mice against DMBA/croton oil-induced skin papillomagenesis, likely due to the chemopreventive activity of high concentrations of antioxidants such as vitamins A, C, and E; glutathione peroxidase; several isozymes of superoxide dismutase; the minerals selenium and zinc; and polysaccharides in aloe vera.
Regulation and Gene Expression of Heme Synthesis Under Heavy Metal Exposure- Review
137-158
10.1615/JEnvironPatholToxicolOncol.v29.i2.70
Avital
Schauder
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
Almog
Avital
The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel
Zvi
Malik
The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Israel
heme
heavy metals
iron
Pb
Ga
ALAD
PBGD
Environmental pollution of heavy metals is very abundant nowadays from industry, chemicals, old paints, and pipes or resulting from previous contaminants accumulating in the food chain. Most of the iron demands of the body are needed for heme synthesis and assembly, but iron is also required for Fe-S cluster proteins and other redox enzymes. Heme is an essential, iron-binding molecule used as a prosthetic group of hemoproteins or as a regulator in multiple cellular pathways. In this review, we focused on the effect of exposure to heavy metals, such as Pb, Ga, Cu, Kd, Hg and Al, on heme synthesis as the main iron-sequestering process of the human body. These metals compete with iron on transporters, reduce the cellular iron pool and moreover, bind to proteins, and cause physical and mental disturbances. Heavy metals mainly impair various aspects of the heme synthesis pathway: gene expression, enzyme activity, and iron integration into protoporphyrin IX. Main risk factors are described as well as effects on iron dependant processes in order to increase public awareness to the distribution of heavy metals in our close environment and the harsh consequences of exposure, even in low doses.
Endotoxin Contamination of Agaricus blazei Murrill Extract Enhances Murine Immunologic Responses and Inhibits the Growth of Sarcoma 180 Implants In Vivo
159-168
10.1615/JEnvironPatholToxicolOncol.v29.i2.80
Hitoshi
Kobayashi
Hokuto Corporation Mushroom Research Laboratory, Shimokomazawa 800-8, Nagano 381-0008, Nagano; and Department of Laboratory Medicine, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan
Junya
Masumoto
Department of Pathology, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Nagano; and Department of Laboratory Medicine, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan
Agaricus blazei Murrill
compost
endotoxin contamination
Sarcoma 180
TNF-a
Agaricus blazei Murrill, a native mushroom of Brazil, has been reported to be an immunoreactant with anti-tumor effect. There are many reports on the anti-tumor effect of Agaricus blazei Murrill; however, the precise mechanism of its effect is not fully understood. In this study, we tried to confirm the anti-tumor effect of Agaricus blazei Murrill against Sarcoma 180 cells in a mouse model and found that an inhibitory effect on tumor growth was induced by peritoneal injection of a freeze-dried, hot water extract of Agaricus blazei Murrill (FAG). We noted that there were differences among each sample in terms of anti-tumor activity. We hypothesized that this was because some contaminants of FAG were affecting the anti-tumor activity. We evaluated cytokine secretion from mouse peritoneal cells incubated with FAG. While high interleukin-6 and tumor necrosis factor-α secretions were observed in response to crude FAG, they were dramatically decreased by the removal of endotoxin from the FAG using an endotoxin-specific polymyxin B-conjugated affinity column. The reductions were synergistically recovered by adding an amount of lipopolysaccharide equivalent to the amount of contaminated endotoxin. Thus, these data suggest that the contaminated endotoxin of Agaricus blazei Murrill may act as an immunomodulator of anti-tumor activity.