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Open AccessArticle Telomere Length Diversity in Cattle Breeds
by , , , , , and
Diversity 2010, 2(9), 1118-1129; doi:10.3390/d2091118
Received: 23 April 2010 / Revised: 26 July 2010 / Accepted: 24 August 2010 / Published: 31 August 2010
Cited by 2 | Viewed by 4874 | PDF Full-text (462 KB) | HTML Full-text | XML Full-text
Abstract
Telomeres are specialized nucleoprotein structures that have two important functions: (i) protection of the chromosomal ends from deleterious events such as chromosome fusion and degradation; (ii) counteraction of the “end replication problem” by allowing telomerase-dependent or, more rarely, telomerase-independent telomere elongation. The DNA
[...] Read more.
Telomeres are specialized nucleoprotein structures that have two important functions: (i) protection of the chromosomal ends from deleterious events such as chromosome fusion and degradation; (ii) counteraction of the “end replication problem” by allowing telomerase-dependent or, more rarely, telomerase-independent telomere elongation. The DNA sequences underlying these activities are short simple tandem repeats, which in vertebrate consist of a variable number of TTAGGG. Telomeres dysfunction may be caused either by the absence of telomerase activity or by mutations in telomeric proteins involved in telomere length and structure regulation. Additionally, increasing experimental evidence suggests that telomeres take part in the complex network regulating cell proliferation. Accordingly, telomeres are involved in biological process such as aging and tumor progression. In this study we determined the telomere length in two bovine Italian cattle breeds, Chianina and Maremmana, which are characterized by high longevity and range breeding. In order to account for possible variation among different tissues, we have determined telomere length in different organs such as spleen, lung and liver. Overall, the median telomere length was significant lower in Chianina (11 ± 0.69 kb) than in Maremmana (12.05 ± 1.57 kb). Moreover, telomere length variation among individuals was very low in Chianina but rather high in Maremmana. These data suggest that telomere length is influenced by the breeds. This hypothesis is confirmed by the different history of these Italian breeds. Indeed, Chianina has a long history and its size was maintained by the Breeders Association without necessity to crossbreed with other breeds, whereas the population of Maremmana underwent a dramatic shrinkage in the recent past. Therefore, breeders have crossed Maremmana with other breeds, like Charolais, and have relaxed the rules for the inclusion in the herd book. Full article
(This article belongs to the Special Issue Biological Diversity Assessed by Molecular Methods)
Open AccessReview Discovery and Development of Anti-HBV Agents and Their Resistance
by , and
Molecules 2010, 15(9), 5878-5908; doi:10.3390/molecules15095878
Received: 4 August 2010 / Revised: 24 August 2010 / Accepted: 26 August 2010 / Published: 27 August 2010
Cited by 29 | Viewed by 7658 | PDF Full-text (642 KB)
Abstract
Hepatitis B virus (HBV) infection is a prime cause of liver diseases such as hepatitis, cirrhosis and hepatocellular carcinoma. The current drugs clinically available are nucleot(s)ide analogues that inhibit viral reverse transcriptase activity. Most drugs of this class are reported to have viral
[...] Read more.
Hepatitis B virus (HBV) infection is a prime cause of liver diseases such as hepatitis, cirrhosis and hepatocellular carcinoma. The current drugs clinically available are nucleot(s)ide analogues that inhibit viral reverse transcriptase activity. Most drugs of this class are reported to have viral resistance with breakthrough. Recent advances in methods for in silico virtual screening of chemical libraries, together with a better understanding of the resistance mechanisms of existing drugs have expedited the discovery and development of novel anti-viral drugs. This review summarizes the current status of knowledge about and viral resistance of HBV drugs, approaches for the development of novel drugs as well as new viral and host targets for future drugs. Full article
(This article belongs to the Special Issue Anti-Infective Agents)
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Open AccessArticle Toxicity of the Herbicide Atrazine: Effects on Lipid Peroxidation and Activities of Antioxidant Enzymes in the Freshwater Fish Channa Punctatus (Bloch)
by , , , , and
Int. J. Environ. Res. Public Health 2010, 7(8), 3298-3312; doi:10.3390/ijerph7083298
Received: 23 July 2010 / Accepted: 23 August 2010 / Published: 24 August 2010
Cited by 73 | Viewed by 5543 | PDF Full-text (316 KB) | HTML Full-text | XML Full-text
Abstract
The present study was undertaken to evaluate the toxicity and effects of a commercial formulation of the herbicide atrazine (Rasayanzine) on lipid peroxidation and antioxidant enzyme system in the freshwater air breathing fish Channa punctatus. The 12, 24, 48, 72 and 96
[...] Read more.
The present study was undertaken to evaluate the toxicity and effects of a commercial formulation of the herbicide atrazine (Rasayanzine) on lipid peroxidation and antioxidant enzyme system in the freshwater air breathing fish Channa punctatus. The 12, 24, 48, 72 and 96 h LC50 of atrazine, calculated by probit analysis, were determined to be 77.091, 64.053, 49.100, 44.412 and 42.381 mg·L-1, respectively, in a semi static system with significant difference (p < 0.05) in LC10-90 values obtained for different times of exposure. In addition to concentration and time dependent decrease in mortality rate, stress signs in the form of behavioral changes were also observed in response to the test chemical. In fish exposed for 15 days to different sublethal concentrations of the herbicide (1/4 LC50 = ~10.600 mg·L-1, 1/8 LC50 = ~5.300 mg·L-1 and 1/10 LC50 = ~4.238 mg·L-1) induction of oxidative stress in the liver was evidence by increased lipid peroxidation levels. The antioxidants superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) responded positively in a concentration dependent pattern, thus, suggesting the use of these antioxidants as potential biomarkers of toxicity associated with contaminations exposure in freshwater fishes. Full article
Open AccessReview Core as a Novel Viral Target for Hepatitis C Drugs
by , , , and
Viruses 2010, 2(8), 1734-1751; doi:10.3390/v2081734
Received: 18 June 2010 / Revised: 6 August 2010 / Accepted: 16 August 2010 / Published: 20 August 2010
Cited by 17 | Viewed by 5224 | PDF Full-text (290 KB) | HTML Full-text | XML Full-text
Abstract
Hepatitis C virus (HCV) infects over 130 million people worldwide and is a major cause of liver disease. No vaccine is available. Novel specific drugs for HCV are urgently required, since the standard-of-care treatment of pegylated interferon combined with ribavirin is poorly tolerated
[...] Read more.
Hepatitis C virus (HCV) infects over 130 million people worldwide and is a major cause of liver disease. No vaccine is available. Novel specific drugs for HCV are urgently required, since the standard-of-care treatment of pegylated interferon combined with ribavirin is poorly tolerated and cures less than half of the treated patients. Promising, effective direct-acting drugs currently in the clinic have been described for three of the ten potential HCV target proteins: NS3/NS4A protease, NS5B polymerase and NS5A, a regulatory phosphoprotein. We here present core, the viral capsid protein, as another attractive, non-enzymatic target, against which a new class of anti-HCV drugs can be raised. Core plays a major role in the virion’s formation, and interacts with several cellular proteins, some of which are involved in host defense mechanisms against the virus. This most conserved of all HCV proteins requires oligomerization to function as the organizer of viral particle assembly. Using core dimerization as the basis of transfer-of-energy screening assays, peptides and small molecules were identified which not only inhibit core-core interaction, but also block viral production in cell culture. Initial chemical optimization resulted in compounds active in single digit micromolar concentrations. Core inhibitors could be used in combination with other HCV drugs in order to provide novel treatments of Hepatitis C. Full article
(This article belongs to the Special Issue Antivirals Against Hepatitis C Virus)
Open AccessReview Targeting HCV Entry For Development of Therapeutics
by , and
Viruses 2010, 2(8), 1718-1733; doi:10.3390/v2081718
Received: 28 June 2010 / Revised: 5 August 2010 / Accepted: 16 August 2010 / Published: 18 August 2010
Cited by 23 | Viewed by 6089 | PDF Full-text (182 KB) | HTML Full-text | XML Full-text
Abstract
Recent progress in defining the molecular mechanisms of Hepatitis C Virus (HCV) entry affords the opportunity to exploit new viral and host targets for therapeutic intervention. Entry inhibitors would limit the expansion of the infected cell reservoir, and would complement the many replication
[...] Read more.
Recent progress in defining the molecular mechanisms of Hepatitis C Virus (HCV) entry affords the opportunity to exploit new viral and host targets for therapeutic intervention. Entry inhibitors would limit the expansion of the infected cell reservoir, and would complement the many replication inhibitors now under development. The current model for the pathway of entry involves the initial docking of the virus onto the cell surface through interactions of virion envelope and associated low density lipoproteins (LDL) with cell surface glycosaminoglycans and lipoprotein receptors, followed by more specific utilization with other hepatocyte membrane proteins: Scavenger Receptor Class B type 1 (SR-BI), CD81, Claudin 1 (CLDN1) and Occludin (OCLN). The use of blockers of these interactions, e.g. specific antibodies, suggests that inhibition of any one step in the entry pathway can inhibit infection. Despite this knowledge base, the tools for compound screening, HCV pseudoparticles (HCVpp) and cell culture virus (HCVcc), and the ability to adapt them to industrial use are only recently available and as a result drug discovery initiatives are in their infancy. Several therapies aiming at modulating the virus envelope to prevent host cell binding are in early clinical testing. The first test case for blocking a cellular co-receptor is an SR-BI modulator. ITX 5061, an orally active small molecule, targets SR-BI and has shown potent antiviral activity against HCVpp and HCVcc. ITX 5061 has exhibited good safety in previous clinical studies, and is being evaluated in the clinic in chronic HCV patients and patients undergoing liver transplantation. Entry inhibitors promise to be valuable players in the future development of curative therapy against HCV. Full article
(This article belongs to the Special Issue Antivirals Against Hepatitis C Virus)
Open AccessReview Interferon-λ in HCV Infection and Therapy
by and
Viruses 2010, 2(8), 1589-1602; doi:10.3390/v2081589
Received: 28 June 2010 / Accepted: 28 July 2010 / Published: 5 August 2010
Cited by 19 | Viewed by 5258 | PDF Full-text (207 KB) | HTML Full-text | XML Full-text
Abstract
Chronic infection with hepatitis C virus (HCV) is associated with significant liver disease and is therefore an important public health problem. The current standard-of-care therapy for chronic HCV infection consists of a combination of pegylated (PEG) interferon (IFN)-α and ribavirin. Although this therapy
[...] Read more.
Chronic infection with hepatitis C virus (HCV) is associated with significant liver disease and is therefore an important public health problem. The current standard-of-care therapy for chronic HCV infection consists of a combination of pegylated (PEG) interferon (IFN)-α and ribavirin. Although this therapy effectively generates a sustained viral response in approximately half of treated individuals, it is associated with significant hematological and neurological side effects. A new family of IFN-related proteins (IFN-λ1, 2, and 3; or alternately, IL-29, 28A, 28B, respectively) possesses properties that may make these cytokines superior to PEG-IFN-α for HCV therapy. Genetic studies have also implicated these proteins in both the natural and therapy-induced resolution of HCV infection. This review summarizes the basic aspects of IFN-λ biology, the potential role of these cytokines in HCV infection, and the outlook for their therapeutic application. Full article
(This article belongs to the Special Issue Antivirals Against Hepatitis C Virus)
Open AccessReview Can Intensive Use of Alcohol-Based Hand Rubs Lead to Passive Alcoholization?
by , and
Int. J. Environ. Res. Public Health 2010, 7(8), 3038-3050; doi:10.3390/ijerph7083038
Received: 28 June 2010 / Revised: 22 July 2010 / Accepted: 27 July 2010 / Published: 30 July 2010
Cited by 9 | Viewed by 7011 | PDF Full-text (204 KB) | HTML Full-text | XML Full-text
Abstract
Hand disinfection with alcohols-based hand rubs (ABHRs) are known to be the most effective measure to prevent nosocomial infections in healthcare. ABHRs contain on average 70% by weight of one or more alcohols. During the hand rubbing procedure, users are exposed to these
[...] Read more.
Hand disinfection with alcohols-based hand rubs (ABHRs) are known to be the most effective measure to prevent nosocomial infections in healthcare. ABHRs contain on average 70% by weight of one or more alcohols. During the hand rubbing procedure, users are exposed to these alcohols not only through dermal contact, but also via inhalation, due to the physical and chemical properties of alcohols volatilizing from alcoholic solutions or gels into the air. Ethanol ingestion is well known to increase risks of several diseases (affecting the pancreas, liver, cardiovascular system…), but there is a lack of knowledge about the effects of exposure to other alcohols (including n- or isopropanol) via inhalation and dermal contact, despite the worldwide use of ABHRs. This work aims at discussing possible health effects related to unintentional alcoholization (via inhalation and dermal contact) from professional ABHR usage to suggest the need for more research in this area (but not to question the value of ABHRs). Based upon an average of 30 hand rubbings per healthcare professional per day, it can be assumed that a healthcare worker may be exposed to a maximum 5,500 mg/m3 per work shift, five times above the recommended occupational time weighted average limit. Thus, in order to answer the question posed in the title, studies on spatial and temporal variability of alcohol emission from ABHRs in real world situations and studies on certain high risk individuals are needed. Full article
Open AccessShort Note Is there Emergence of Clinical HBV Resistance Under Long-Term HBV Combination Therapy? A Challenging Case Report
by , , , , , and
Viruses 2010, 2(8), 1564-1570; doi:10.3390/v2081564
Received: 24 June 2010 / Revised: 16 July 2010 / Accepted: 28 July 2010 / Published: 29 July 2010
Cited by 1 | Viewed by 4834 | PDF Full-text (80 KB) | HTML Full-text | XML Full-text
Abstract
A first case of clinical tenofovir (TDF) HBV resistance in an HIV/HBV coinfected patient who developed an acute flare of hepatitis B is reported. The clinical course was accompanied by signs of acute liver failure after being on successful HBV treatment with tenofovir
[...] Read more.
A first case of clinical tenofovir (TDF) HBV resistance in an HIV/HBV coinfected patient who developed an acute flare of hepatitis B is reported. The clinical course was accompanied by signs of acute liver failure after being on successful HBV treatment with tenofovir and persistently undetectable HBV-DNA viral load for over five years. Full article
Open AccessReview Nonsteroidal Anti-Inflammatory Drugs and the Kidney
by
Pharmaceuticals 2010, 3(7), 2291-2321; doi:10.3390/ph3072291
Received: 30 June 2010 / Revised: 16 July 2010 / Accepted: 20 July 2010 / Published: 21 July 2010
Cited by 13 | Viewed by 5785 | PDF Full-text (225 KB) | HTML Full-text | XML Full-text
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the isoenzymes COX-1 and COX-2 of cyclooxygenase (COX). Renal side effects (e.g., kidney function, fluid and urinary electrolyte excretion) vary with the extent of COX-2-COX-1 selectivity and the administered dose of these compounds. While young healthy subjects will
[...] Read more.
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the isoenzymes COX-1 and COX-2 of cyclooxygenase (COX). Renal side effects (e.g., kidney function, fluid and urinary electrolyte excretion) vary with the extent of COX-2-COX-1 selectivity and the administered dose of these compounds. While young healthy subjects will rarely experience adverse renal effects with the use of NSAIDs, elderly patients and those with co-morbibity (e.g., congestive heart failure, liver cirrhosis or chronic kidney disease) and drug combinations (e.g., renin-angiotensin blockers, diuretics plus NSAIDs) may develop acute renal failure. This review summarizes our present knowledge how traditional NSAIDs and selective COX-2 inhibitors may affect the kidney under various experimental and clinical conditions, and how these drugs may influence renal inflammation, water transport, sodium and potassium balance and how renal dysfunction or hypertension
may result. Full article
(This article belongs to the Special Issue Non-Steroidal Anti-Inflammatory Drugs)
Open AccessReview YKL-40—A Protein in the Field of Translational Medicine: A Role as a Biomarker in Cancer Patients?
by and
Cancers 2010, 2(3), 1453-1491; doi:10.3390/cancers2031453
Received: 13 May 2010 / Revised: 1 July 2010 / Accepted: 9 July 2010 / Published: 12 July 2010
Cited by 16 | Viewed by 5415 | PDF Full-text (649 KB) | HTML Full-text | XML Full-text
Abstract
YKL-40 is a 40 kDa glycoprotein produced by cancer cells, inflammatory cells and stem cells. It probably has a role in cell proliferation and differentiation, inflammation, protection against apoptosis, stimulation of angiogenesis, and regulation of extracellular tissue remodelling. Plasma levels of YKL-40 are
[...] Read more.
YKL-40 is a 40 kDa glycoprotein produced by cancer cells, inflammatory cells and stem cells. It probably has a role in cell proliferation and differentiation, inflammation, protection against apoptosis, stimulation of angiogenesis, and regulation of extracellular tissue remodelling. Plasma levels of YKL-40 are often elevated in patients with localized or advanced cancer compared to age-matched healthy subjects. Several studies have demonstrated that high plasma YKL-40 is an independent prognostic biomarker of short survival in patients with different types of cancer. However, there is not yet sufficient data to support determination of plasma YKL-40 outside research projects as a biomarker for screening of gastrointestinal cancer and determination of treatment response and poor prognosis before or during treatment and follow-up. Plasma YKL-40 is also elevated in patients with other diseases than cancer, e.g., severe infections, cardiovascular disease, diabetes, chronic obstructive lung disease, asthma, liver fibrosis and rheumatoid arthritis. Co-morbidity should therefore always be considered in patients with cancer, since other sources than cancer cells can increase plasma YKL-40 levels. Future focused translational research projects combining basic and clinical research are needed in a joint effort to answer questions of the complex function and regulation of YKL-40 and the question if plasma YKL-40 is a clinical useful biomarker in patients with cancer. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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Open AccessReview Models of Hepatocellular Carcinoma and Biomarker Strategy
by and
Cancers 2010, 2(3), 1441-1452; doi:10.3390/cancers2031441
Received: 3 June 2010 / Revised: 2 July 2010 / Accepted: 6 July 2010 / Published: 7 July 2010
Cited by 10 | Viewed by 5142 | PDF Full-text (303 KB) | HTML Full-text | XML Full-text
Abstract
The overwhelming need to improve preclinical models in oncology has stimulated research efforts to refine and validate robust orthotopic models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Sophisticated technologies including bioluminescence,
[...] Read more.
The overwhelming need to improve preclinical models in oncology has stimulated research efforts to refine and validate robust orthotopic models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Sophisticated technologies including bioluminescence, contrast enhanced ultrasound imaging, positron emission tomography, computed tomography and magnetic resonance imaging have been added to existing serum- and histology-based biomarkers to assist with patient selection and the design of clinical trials. The rationale for the use of human hepatocellular carcinoma (HCC) cell lines, implementation of xenograft and orthotopic animal models and utilization of available biomarkers have been discussed, providing guidelines to facilitate preclinical research for the development of treatments for HCC patients. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessArticle Solid-Phase Synthesis of the Lipopeptide Myr-HBVpreS/2-78, a Hepatitis B Virus Entry Inhibitor
by , , , , and
Molecules 2010, 15(7), 4773-4783; doi:10.3390/molecules15074773
Received: 20 May 2010 / Revised: 2 July 2010 / Accepted: 5 July 2010 / Published: 7 July 2010
Cited by 8 | Viewed by 9906 | PDF Full-text (306 KB)
Abstract
Chronic HBV infection is the leading cause of liver cirrhosis and hepatocellular carcinoma (HCC). Synthetic peptides derived from the N-terminus of the large HBV envelope protein (L-protein) have been shown to efficiently block HBV entry. Myr-HBVpreS/2-78, the parent compound of these drugs,
[...] Read more.
Chronic HBV infection is the leading cause of liver cirrhosis and hepatocellular carcinoma (HCC). Synthetic peptides derived from the N-terminus of the large HBV envelope protein (L-protein) have been shown to efficiently block HBV entry. Myr-HBVpreS/2-78, the parent compound of these drugs, inhibits human HBV infection in vitro and in vivo. An efficient synthesis is required, as these peptides constitute a novel class of anti HBV drugs. Consequently, the solid phase synthesis of the N-terminal 77 amino acids of the viral L-protein was studied in detail. The peptide was N-terminally myristoylated to resemble the natural, postranslationally modified protein. The synthesis was monitored using the Fmoc cleavage pattern of the solid phase synthesis on a standard peptide synthesizer and by LC-MS analyses of the arising side products. “Difficult sequences” in the positions 42-47 of the peptide sequence complicate the efficient synthesis of the 77-mer peptide HBVpreS/2-78. Attempts were undertaken to optimize the synthesis by heating, double coupling or the use of pseudoproline dipeptides. HPLC-MS analyses showed that the efficiency of the synthesis could be increased best by temperature elevation. This resulted in a higher purity of the crude product after solid phase synthesis. It was possible to minimize the occurrence of side products due to the positive effects related to higher reaction temperature. In conclusion, the peptide is accessible by stepwise SPPS without the necessity of segment coupling. Full article
(This article belongs to the Special Issue Solid Phase Synthesis)
Open AccessReview Innate Antiviral Immune Responses to Hepatitis B Virus
by , , and
Viruses 2010, 2(7), 1394-1410; doi:10.3390/v2071394
Received: 4 June 2010 / Revised: 22 June 2010 / Accepted: 1 July 2010 / Published: 5 July 2010
Cited by 33 | Viewed by 8238 | PDF Full-text (329 KB) | HTML Full-text | XML Full-text
Abstract
Hepatitis B virus (HBV) is a major cause of acute and chronic hepatitis in humans. As HBV itself is currently viewed as a non-cytopathic virus, the liver pathology associated with hepatitis B is mainly thought to be due to immune responses directed against
[...] Read more.
Hepatitis B virus (HBV) is a major cause of acute and chronic hepatitis in humans. As HBV itself is currently viewed as a non-cytopathic virus, the liver pathology associated with hepatitis B is mainly thought to be due to immune responses directed against HBV antigens. The outcome of HBV infection is the result of complex interactions between replicating HBV and the immune system. While the role of the adaptive immune response in the resolution of HBV infection is well understood, the contribution of innate immune mechanisms remains to be clearly defined. The innate immune system represents the first line of defense against viral infection, but its role has been difficult to analyze in humans due to late diagnosis of HBV infection. In this review, we discuss recent advances in the field of innate immunity to HBV infection. Full article
(This article belongs to the Special Issue Hepatitis Viruses)
Open AccessArticle Antioxidant Properties of European Cranberrybush Fruit (Viburnum opulus var. edule)
by , , , , and
Molecules 2010, 15(6), 4467-4477; doi:10.3390/molecules15064467
Received: 5 May 2010 / Revised: 22 June 2010 / Accepted: 22 June 2010 / Published: 23 June 2010
Cited by 27 | Viewed by 10369 | PDF Full-text (103 KB)
Abstract
In the literature there is little available information concerning European cranberrybush fruit (Viburnum opulus var. edule). This plant can be cultivated, even in harsh climatic conditions, because of its low environmental demands, and it is possible to harvest the fruit even
[...] Read more.
In the literature there is little available information concerning European cranberrybush fruit (Viburnum opulus var. edule). This plant can be cultivated, even in harsh climatic conditions, because of its low environmental demands, and it is possible to harvest the fruit even in the snow cover. The aim of this study was to determine the content of polyphenolics, antioxidant activity, flavonoids and vitamin C in the fruit of three cultivars ´Leningradskaya otbornaya´, ´Souzga´ and ´Taezny rubiny´ of this species. In the case of polyphenolics, high contents [up to 8.29 g of gallic acid/kg of fresh mass (FM)] were observed. The 1,1´-diphenyl-2-picrylhydrazyl (DPPH) and 2,2´-azinobis-3-ethyl-benzthiazino-6-sulphonic acid (ABTS) tests were applied to determine antioxidant activity, which was also high in comparison with other fruit species. The corresponding correlations between the polyphenolic content and antioxidant activity were in case of the DPPH test r2 = 0.88 and for the ABTS test r2 = 0.98. For comparison, the scavenging activity towards reactive oxygen species (superoxide anion, hydroxyl radical and nitric oxide) was determined by using a 25% fruit extract of particular cultivars. Antioxidant efficiency was also assessed using the rat liver slice model. Furthermore, the contents of flavonoids and vitamin C were assayed, giving values of 4.89 g/kg and 1.64 g/kg FM, respectively. The work should contribute to the popularization of this species as a promising crop plant in human nutrition. Full article
(This article belongs to the Special Issue Antioxidants)
Open AccessArticle Ochratoxin A: In Utero Exposure in Mice Induces Adducts in Testicular DNA
by , , , , and
Toxins 2010, 2(6), 1428-1444; doi:10.3390/toxins2061428
Received: 15 April 2010 / Revised: 26 May 2010 / Accepted: 8 June 2010 / Published: 11 June 2010
Cited by 31 | Viewed by 5635 | PDF Full-text (433 KB) | HTML Full-text | XML Full-text
Abstract
Ochratoxin A (OTA) is a nephrotoxin and carcinogen that is associated with Balkan endemic nephropathy and urinary tract tumors. OTA crosses the placenta and causes adducts in the liver and kidney DNA of newborns. Because the testis and kidney develop from the same
[...] Read more.
Ochratoxin A (OTA) is a nephrotoxin and carcinogen that is associated with Balkan endemic nephropathy and urinary tract tumors. OTA crosses the placenta and causes adducts in the liver and kidney DNA of newborns. Because the testis and kidney develop from the same embryonic tissue, we reasoned that OTA also may cause adducts transplacentally in the testis. We tested the hypothesis that acute exposure to OTA, via food and via exposure in utero, causes adducts in testicular DNA and that these lesions are identical to those that can be produced in the kidney and testis by the consumption of OTA. Adult mice received a single dose of OTA (from 0–1,056 µg/kg) by gavage. Pregnant mice received a single i.p. injection of OTA (2.5 mg/kg) at gestation day 17. DNA adducts were determined by 32P-postlabeling. Gavage-fed animals sacrificed after 48 hours accumulated OTA in kidney and testis and showed DNA adducts in kidney and testis. Some OTA metabolites isolated from the tissues were similar in both organs (kidney and testis). The litters of mice exposed prenatally to OTA showed no signs of overt toxicity. However, newborn and 1-month old males had DNA adducts in kidney and testis that were chromatographically similar to DNA adducts observed in the kidney and testis of gavage-fed adults. One adduct was identified previously as C8-dG-OTA adduct by LC MS/MS. No adducts were observed in males from dams not exposed to OTA. Our findings that in utero exposure to OTA causes adducts in the testicular DNA of male offspring support a possible role for OTA in testicular cancer. Full article
(This article belongs to the Special Issue Ochratoxins)
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Open AccessReview Molecular Mechanism of Ochratoxin A Transport in the Kidney
by , and
Toxins 2010, 2(6), 1381-1398; doi:10.3390/toxins2061381
Received: 15 April 2010 / Revised: 11 May 2010 / Accepted: 9 June 2010 / Published: 9 June 2010
Cited by 19 | Viewed by 4929 | PDF Full-text (326 KB) | HTML Full-text | XML Full-text
Abstract
The mycotoxin, ochratoxin A (OTA), is thought to be responsible for Balkan endemic nephropathy. OTA accumulates in several tissues, especially in the kidneys and liver. The excretion of OTA into urine is thought to be mainly by tubular secretion, presumably via the organic
[...] Read more.
The mycotoxin, ochratoxin A (OTA), is thought to be responsible for Balkan endemic nephropathy. OTA accumulates in several tissues, especially in the kidneys and liver. The excretion of OTA into urine is thought to be mainly by tubular secretion, presumably via the organic anion transport system. Recently, several families of multispecific organic anion transporters have been identified: organic anion transporters (OATs), organic anion-transporting polypeptides (OATPs), oligopeptide transporters (PEPTs), and ATP-binding cassette (ABC) transporters, such as MRP2 and BCRP. These renal transporters mediate the transmembrane transport of OTA and play a pivotal role in the development of OTA-induced nephrotoxicity. Full article
(This article belongs to the Special Issue Ochratoxins)
Open AccessReview The Role of PAS Kinase in PASsing the Glucose Signal
by and
Sensors 2010, 10(6), 5668-5682; doi:10.3390/s100605668
Received: 4 February 2010 / Revised: 20 March 2010 / Accepted: 12 May 2010 / Published: 4 June 2010
Cited by 9 | Viewed by 6450 | PDF Full-text (4234 KB) | HTML Full-text | XML Full-text
Abstract
PAS kinase is an evolutionarily conserved nutrient responsive protein kinase that regulates glucose homeostasis. Mammalian PAS kinase is activated by glucose in pancreatic beta cells, and knockout mice are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet.
[...] Read more.
PAS kinase is an evolutionarily conserved nutrient responsive protein kinase that regulates glucose homeostasis. Mammalian PAS kinase is activated by glucose in pancreatic beta cells, and knockout mice are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet. Yeast PAS kinase is regulated by both carbon source and cell integrity stress and stimulates the partitioning of glucose toward structural carbohydrate biosynthesis. In our current model for PAS kinase regulation, a small molecule metabolite binds the sensory PAS domain and activates the enzyme. Although bona fide PAS kinase substrates are scarce, in vitro substrate searches provide putative targets for exploration. Full article
(This article belongs to the Special Issue Glucose Sensors)
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Open AccessCommunication Anti-Proliferative Effect of Camellianin A in Adinandra nitida Leaves and Its Apoptotic Induction in Human Hep G2 and MCF-7 Cells
by , , and
Molecules 2010, 15(6), 3878-3886; doi:10.3390/molecules15063878
Received: 1 April 2010 / Revised: 14 May 2010 / Accepted: 24 May 2010 / Published: 28 May 2010
Cited by 7 | Viewed by 5545 | PDF Full-text (304 KB)
Abstract
Leaves of Adinandra nitida constitute a kind of flavonoid-rich plant food. In this study, camellianin A, the main flavonoid in the leaves of Adinandra nitida,was prepared and identified by high performance liquid chromatography-photodiode array detector-electrospray ionization mass spectrometry (HPLC-PDA-ESI/MS). In the anticancer
[...] Read more.
Leaves of Adinandra nitida constitute a kind of flavonoid-rich plant food. In this study, camellianin A, the main flavonoid in the leaves of Adinandra nitida,was prepared and identified by high performance liquid chromatography-photodiode array detector-electrospray ionization mass spectrometry (HPLC-PDA-ESI/MS). In the anticancer assay, it was found camellianin A could inhibit the proliferation of the human hepatocellular liver carcinoma Hep G2 and human breast adenocarcinoma MCF-7 cell lines in a dose-dependent manner and induce the significant increase of the G0/G1 cell population. After treated by camellianin A, phosphatidylserine of Hep G2 and MCF-7 cells could translocate significantly to the surface of the membrane. The increase of an early apoptotic population of Hep G2 and MCF-7 cells was observed. It was concluded that camellianin A not only affected the progress of the cell cycle, but also induced cells to enter into apoptosis. Full article
Open AccessReview Viruses and Breast Cancer
by and
Cancers 2010, 2(2), 752-772; doi:10.3390/cancers2020752
Received: 8 March 2010 / Revised: 7 April 2010 / Accepted: 26 April 2010 / Published: 30 April 2010
Cited by 12 | Viewed by 7374 | PDF Full-text (332 KB) | HTML Full-text | XML Full-text
Abstract
Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify
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Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix. Full article
(This article belongs to the Special Issue Breast Cancer)
Open AccessReview Impact of Dietary Polyphenols on Carbohydrate Metabolism
by , , , , , and
Int. J. Mol. Sci. 2010, 11(4), 1365-1402; doi:10.3390/ijms11041365
Received: 24 February 2010 / Revised: 24 March 1995 / Accepted: 25 March 2010 / Published: 31 March 2010
Cited by 304 | Viewed by 15694 | PDF Full-text (312 KB) | HTML Full-text | XML Full-text
Abstract
Polyphenols, including flavonoids, phenolic acids, proanthocyanidins and resveratrol, are a large and heterogeneous group of phytochemicals in plant-based foods, such as tea, coffee, wine, cocoa, cereal grains, soy, fruits and berries. Growing evidence indicates that various dietary polyphenols may influence carbohydrate metabolism at
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Polyphenols, including flavonoids, phenolic acids, proanthocyanidins and resveratrol, are a large and heterogeneous group of phytochemicals in plant-based foods, such as tea, coffee, wine, cocoa, cereal grains, soy, fruits and berries. Growing evidence indicates that various dietary polyphenols may influence carbohydrate metabolism at many levels. In animal models and a limited number of human studies carried out so far, polyphenols and foods or beverages rich in polyphenols have attenuated postprandial glycemic responses and fasting hyperglycemia, and improved acute insulin secretion and insulin sensitivity. The possible mechanisms include inhibition of carbohydrate digestion and glucose absorption in the intestine, stimulation of insulin secretion from the pancreatic b-cells, modulation of glucose release from the liver, activation of insulin receptors and glucose uptake in the insulin-sensitive tissues, and modulation of intracellular signalling pathways and gene expression. The positive effects of polyphenols on glucose homeostasis observed in a large number of in vitro and animal models are supported by epidemiological evidence on polyphenol-rich diets. To confirm the implications of polyphenol consumption for prevention of insulin resistance, metabolic syndrome and eventually type 2 diabetes, human trials with well-defined diets, controlled study designs and clinically relevant end-points together with holistic approaches e.g., systems biology profiling technologies are needed. Full article
(This article belongs to the Special Issue Phenolics and Polyphenolics)
Open AccessArticle Alcohol and HCV Chronic Infection Are Risk Cofactors of Type 2 Diabetes Mellitus for Hepatocellular Carcinoma in Italy
by , , , , , , , , , and
Int. J. Environ. Res. Public Health 2010, 7(4), 1366-1378; doi:10.3390/ijerph7041366
Received: 3 December 2009 / Revised: 8 February 2010 / Accepted: 15 March 2010 / Published: 29 March 2010
Cited by 11 | Viewed by 6048 | PDF Full-text (170 KB) | HTML Full-text | XML Full-text
Abstract
Type 2 diabetes mellitus (DM2) has been associated with hepatocellular carcinoma (HCC) development. To study this relationship, we enrolled 465 HCC patients compared with 618 Cirrhotic cases and 490 Controls. The prevalence of DM2 is significantly higher in HCC patients with an Odds
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Type 2 diabetes mellitus (DM2) has been associated with hepatocellular carcinoma (HCC) development. To study this relationship, we enrolled 465 HCC patients compared with 618 Cirrhotic cases and 490 Controls. The prevalence of DM2 is significantly higher in HCC patients with an Odds Ratio of 3.12 versus Controls. In HCC cases with alcohol abuse, the frequency of DM2 is the highest. In our HCC patients, when HCV infection is associated with alcohol abuse, the liver cancer develops earlier. In addition, multivariate analysis shows that alcohol consumption is an independent risk factor for HCC more relevant than HCV infection. Full article
(This article belongs to the Special Issue Alcohol and Public Health)
Open AccessReview Leg Length, Body Proportion, and Health: A Review with a Note on Beauty
by and
Int. J. Environ. Res. Public Health 2010, 7(3), 1047-1075; doi:10.3390/ijerph7031047
Received: 16 December 2009 / Revised: 28 January 2010 / Accepted: 8 March 2010 / Published: 11 March 2010
Cited by 99 | Viewed by 15105 | PDF Full-text (509 KB) | HTML Full-text | XML Full-text
Abstract
Decomposing stature into its major components is proving to be a useful strategy to assess the antecedents of disease, morbidity and death in adulthood. Human leg length (femur + tibia), sitting height (trunk length + head length) and their proportions, for example, (leg
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Decomposing stature into its major components is proving to be a useful strategy to assess the antecedents of disease, morbidity and death in adulthood. Human leg length (femur + tibia), sitting height (trunk length + head length) and their proportions, for example, (leg length/stature), or the sitting height ratio (sitting height/stature × 100), among others) are associated with epidemiological risk for overweight (fatness), coronary heart disease, diabetes, liver dysfunction and certain cancers. There is also wide support for the use of relative leg length as an indicator of the quality of the environment for growth during infancy, childhood and the juvenile years of development. Human beings follow a cephalo-caudal gradient of growth, the pattern of growth common to all mammals. A special feature of the human pattern is that between birth and puberty the legs grow relatively faster than other post-cranial body segments. For groups of children and youth, short stature due to relatively short legs (i.e., a high sitting height ratio) is generally a marker of an adverse environment. The development of human body proportions is the product of environmental x genomic interactions, although few if any specific genes are known. The HOXd and the short stature homeobox-containing gene (SHOX) are genomic regions that may be relevant to human body proportions. For example, one of the SHOX related disorders is Turner syndrome. However, research with non-pathological populations indicates that the environment is a more powerful force influencing leg length and body proportions than genes. Leg length and proportion are important in the perception of human beauty, which is often considered a sign of health and fertility. Full article
(This article belongs to the Special Issue Advances in Epidemiology)
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Open AccessArticle Aflatoxin Contamination in Food and Body Fluids in Relation to Malnutrition and Cancer Status in Cameroon
by , and
Int. J. Environ. Res. Public Health 2010, 7(1), 178-188; doi:10.3390/ijerph7010178
Received: 16 November 2009 / Accepted: 18 December 2009 / Published: 18 January 2010
Cited by 53 | Viewed by 6266 | PDF Full-text (264 KB) | HTML Full-text | XML Full-text
Abstract
Aflatoxins are food contaminants usually associated with hepatitis, immunodepression, impairment of fertility and cancer. The present work was to determine the presence of aflatoxins in eggs, milk, urine, and blood samples that were collected from various sources and periods; and hepatitis B virus
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Aflatoxins are food contaminants usually associated with hepatitis, immunodepression, impairment of fertility and cancer. The present work was to determine the presence of aflatoxins in eggs, milk, urine, and blood samples that were collected from various sources and periods; and hepatitis B virus antigen in blood samples. Aflatoxin was found in eggs (45.2%), cow raw milk (15.9%), breast milk (4.8%), urine from kwashiorkor and marasmic kwashiorkor children (45.5%), and sera from primary liver cancer patients (63.9%); HbsAg was also detected in 69.4% of the serum samples, but there was no association between both factors. Both AF and hepatitis B virus seem to be risk factors that could increase the incidence and prevalence rates of malnutrition and cancer in Cameroon. Full article
Open AccessArticle The Study of the Inhibition of the Recombinant TACE Prodomain to Endotoxemia in Mice
by , , and
Int. J. Mol. Sci. 2009, 10(12), 5442-5454; doi:10.3390/ijms10125442
Received: 9 October 2009 / Accepted: 17 December 2009 / Published: 18 December 2009
Cited by 6 | Viewed by 6821 | PDF Full-text (539 KB) | HTML Full-text | XML Full-text
Abstract
Objective: To demonstrate the inhibitory function of the prodomain of tumor necrosis factor-α (TNF-α) converting enzyme (TACE) on TACE activity and to develop an approach to interfere with inflammation processes. Methods: The cDNA encoding the fulllength ectodomain (T1300) and prodomain (T591) of TACE
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Objective: To demonstrate the inhibitory function of the prodomain of tumor necrosis factor-α (TNF-α) converting enzyme (TACE) on TACE activity and to develop an approach to interfere with inflammation processes. Methods: The cDNA encoding the fulllength ectodomain (T1300) and prodomain (T591) of TACE were amplified by RT-PCR. The expression plasmids (pET-28a (+)-T1300 and pET-28a (+)-T591) were constructed and transformed into E. coli BL21. After Ni2+-NTA resin affinity chromatography, the recombinant T591 protein was obtained and assayed. In order to detect its inhibiton of TACE activity, the mice in the LPS-induced endotoxemia model group were treated with the recombinant TACE prodomain protein prior to the injection of LPS. Murine peritoneal macrophages were isolated from mice abdominal cavity for FCM and the liver, kidney and lung were removed for traditionally histopathology sectioning. Results: The FCM results showed that the recombinant prodomain protein decreased the release of the sTNF-α, which mediated the accumulation of TNF-α on the surface of macrophage cells. HE staining proved that the recombinant protein can decrease the inflammatory response in internal organs of endotoxaemia mice. Conclusions: The recombinant prodomain of TACE has the ability to inhibit sTNF-α release, which indicates that prodomain is an effective antagonist of TACE and might be useful in the molecular design of anti-inflammatory drugs. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
Open AccessArticle Antioxidant and Immunomodulatory Activity of the Alkaloidal Fraction of Cissampelos pareira Linn.
by and
Sci. Pharm. 2010, 78(1), 21-32; doi:10.3797/scipharm.0904-16
Received: 20 April 2009 / Accepted: 4 December 2009 / Published: 6 December 2009
Cited by 12 | Viewed by 185 | PDF Full-text (189 KB)
Abstract
The alkaloidal fraction (AFCP) of roots of Cissampelos pareira Linn. was screened for in-vitro antioxidant activity and immunomodulatory activity in mice. The HPTLC finger print profile was also established for the identification of AFCP which was found to contain 0.176 % of berberine.
[...] Read more.
The alkaloidal fraction (AFCP) of roots of Cissampelos pareira Linn. was screened for in-vitro antioxidant activity and immunomodulatory activity in mice. The HPTLC finger print profile was also established for the identification of AFCP which was found to contain 0.176 % of berberine. AFCP possess strong antioxidant activity which was revealed by its ability to scavenge the stable free radical DPPH, superoxide ion and to inhibit lipid peroxidation in rat liver homogenate induced by iron/ADP/Ascorbate complex. AFCP was found to have significant immunosuppressive activity at lower doses (25 and 50 mg/kg) while no activity was observed at higher doses (75 and 100 mg/kg). Humoral antibody titre was significantly (p<0.01) lowered by AFCP at the doses of 25 and 50 mg/kg. Delayed type hypersensitivity response was also significantly (p<0.01) suppressed by the AFCP at the dose of 75 mg/kg. Thus the present study revealed the immunosuppressive and antioxidant activities of the alkaloidal fraction of C. pareira roots. Full article
Open AccessReview HCV Innate Immune Responses
by
Viruses 2009, 1(3), 1073-1088; doi:10.3390/v1031073
Received: 27 August 2009 / Revised: 25 November 2009 / Accepted: 26 November 2009 / Published: 30 November 2009
Cited by 4 | Viewed by 6125 | PDF Full-text (396 KB) | HTML Full-text | XML Full-text
Abstract
Hepatitis C virus (HCV) establishes a persistent infection in more than 70% of infected individuals. This striking ability to evade the powerful innate immune system results from viral interference occurring at several levels of the interferon (IFN) system. There is strong evidence from
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Hepatitis C virus (HCV) establishes a persistent infection in more than 70% of infected individuals. This striking ability to evade the powerful innate immune system results from viral interference occurring at several levels of the interferon (IFN) system. There is strong evidence from cell culture experiments that HCV can inhibit the induction of IFNβ by cleaving important proteins in the virus sensory pathways of cells such as MAVS and TRIF. There is also evidence that HCV interferes with IFNα signaling through the Jak-STAT pathway, and that HCV proteins target IFN effector systems such as protein kinase R (PKR). These in vitro findings will have to be confirmed in clinical trials investigating the molecular mechanisms of HCV interference with the innate immune system in liver samples. Full article
(This article belongs to the Special Issue Hepatitis Viruses)
Open AccessArticle Dietary Supplementation with Conjugated Linoleic Acid Plus n-3 Polyunsaturated Fatty Acid Increases Food Intake and Brown Adipose Tissue in Rats
by , , , , , , and
Nutrients 2009, 1(2), 178-196; doi:10.3390/nu1020178
Received: 15 October 2009 / Accepted: 24 November 2009 / Published: 26 November 2009
Cited by 7 | Viewed by 6615 | PDF Full-text (830 KB) | HTML Full-text | XML Full-text
Abstract
The effect of supplementation with 1% conjugated linoleic acid and 1% n-3 long chain polyunsaturated fatty acids (CLA/n-3) was assessed in rats. Food intake increased with no difference in body weights. White adipose tissue weights were reduced whereas brown adipose
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The effect of supplementation with 1% conjugated linoleic acid and 1% n-3 long chain polyunsaturated fatty acids (CLA/n-3) was assessed in rats. Food intake increased with no difference in body weights. White adipose tissue weights were reduced whereas brown adipose tissue and uncoupling protein-1 expression were increased. Plasma adiponectin, triglyceride and cholesterol levels were reduced while leptin, ghrelin and liver weight and lipid content were unchanged. Hypothalamic gene expression measurements revealed increased expression of orexigenic and decreased expression of anorexigenic signals. Thus, CLA/n-3 increases food intake without affecting body weight potentially through increasing BAT size and up-regulating UCP-1 in rats. Full article
(This article belongs to the Special Issue Obesity, Nutrition and Dietetics)
Open AccessArticle Antioxidant Effects of Some Drugs on Immobilization Stress Combined with Cold Restraint Stress
by , , , , and
Molecules 2009, 14(11), 4505-4516; doi:10.3390/molecules14114505
Received: 7 September 2009 / Revised: 20 October 2009 / Accepted: 9 November 2009 / Published: 10 November 2009
Cited by 11 | Viewed by 6580 | PDF Full-text (354 KB)
Abstract
The aim of this work was to investigate the effect on antioxidant potential of some commonly used drugs (morphine, tramadol, bromocriptine, haloperidol and azithromycin) on immobilization stress (IS) combined with cold restraint stress (CRS) in the rat. After the drug treatment the animals
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The aim of this work was to investigate the effect on antioxidant potential of some commonly used drugs (morphine, tramadol, bromocriptine, haloperidol and azithromycin) on immobilization stress (IS) combined with cold restraint stress (CRS) in the rat. After the drug treatment the animals were kept immobilized in the cold chamber at 4±0.3ºC for 3 hours and then decapitaed and the livers were extracted. The following parameters were determined in the liver homogenate: content of reduced glutathione, activities of catalase, xanthine oxidase, glutathione reductase, glutathione peroxidase, peroxidase, and lipid peroxidation intensity. A battery of biochemical assays was used and the resulting data were statistically analyzed. Combined stress exhibited a prooxidative action (increased catalase activity, lowered content of reduced glutathione). Significantly enhanced catalase activity that was observed in all groups compared to the control indicates that the primary reactive oxygen species (ROS) metabolite is hydrogen peroxide, which decomposes very rapidly (very high catalase activity), thus hindering formation of OH radicals as the most toxic ROS. None of the tested drugs showed a protective effect on combined IS and CRS. The intensity of lipid peroxidation did not change either in the combined stress or under additional influence of the drugs. Probably, under our experimental conditions, the time was not sufficiently long to observe damage of lipid membrane by ROS. Full article
Open AccessReview Murine Coronavirus Cell Type Dependent Interaction with the Type I Interferon Response
by and
Viruses 2009, 1(3), 689-712; doi:10.3390/v1030689
Received: 2 September 2009 / Revised: 30 October 2009 / Accepted: 4 November 2009 / Published: 4 November 2009
Cited by 16 | Viewed by 6792 | PDF Full-text (352 KB) | HTML Full-text | XML Full-text
Abstract
Coronaviruses infect many species of animal including humans, causing acute and chronic diseases of many organ systems. Murine coronavirus, mouse hepatitis virus (MHV) infection of the mouse, provides animal models for the study of central nervous system disease, including encephalitis and demyelinating diseases
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Coronaviruses infect many species of animal including humans, causing acute and chronic diseases of many organ systems. Murine coronavirus, mouse hepatitis virus (MHV) infection of the mouse, provides animal models for the study of central nervous system disease, including encephalitis and demyelinating diseases such as Multiple Sclerosis and for hepatitis. While there are many studies of the adaptive immune response to MHV, there has until recently been scant information on the type I interferon (IFN) response to MHV. The relationship between MHV and the IFN-α/β response is paradoxical. While the type I IFN response is a crucial aspect of host defense against MHV in its natural host, there is little if any induction of IFN following infection of mouse fibroblast cell lines in vitro. Furthermore, MHV is relatively resistant to the antiviral effects of IFN-α/β in mouse fibroblast cell lines and in human 293T cells. MHV can, under some circumstances, compromise the antiviral effects of IFN signaling. The nucleocapsid protein as well as the nsp1 and nsp3 proteins of MHV has been reported to have IFN antagonist activity. However, in primary cell types such as plasmacytoid dendritic cells (pDC) and macrophages, IFN is induced by MHV infection and an antiviral state is established. Other primary cell types such as neurons, astrocytes and hepatocytes fail to produce IFN following infection and, in vivo, likely depend on IFN produced by pDCs and macrophages for protection from MHV. Thus MHV induction of IFN-α/β and the ability to induce an antiviral state in response to interferon is extremely cell type dependent. IFN induced protection from MHV pathogenesis likely requires the orchestrated activities of several cell types, however, the cell types involved in limiting MHV replication may be different in the liver and in the immune privileged CNS. Full article
(This article belongs to the Special Issue Interferon Antiviral Response and Viral Evasion)
Open AccessArticle Activation of Hepatic Lipase Expression by Oleic Acid: Possible Involvement of USF1
by , , , , and
Nutrients 2009, 1(2), 133-147; doi:10.3390/nu1020133
Received: 7 October 2009 / Accepted: 28 October 2009 / Published: 29 October 2009
Cited by 4 | Viewed by 7219 | PDF Full-text (460 KB) | HTML Full-text | XML Full-text
Abstract
Polyunsaturated fatty acids affect gene expression mainly through peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element binding proteins (SREBPs), but how monounsaturated fatty acids affect gene expression is poorly understood. In HepG2 cells, oleate supplementation has been shown to increase secretion of hepatic
[...] Read more.
Polyunsaturated fatty acids affect gene expression mainly through peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element binding proteins (SREBPs), but how monounsaturated fatty acids affect gene expression is poorly understood. In HepG2 cells, oleate supplementation has been shown to increase secretion of hepatic lipase (HL). We hypothesized that oleate affects HL gene expression at the transcriptional level. To test this, we studied the effect of oleate on HL promoter activity using HepG2 cells and the proximal HL promoter region (700 bp). Oleate increased HL expression and promoter activity 1.3–2.1 fold and reduced SREBP activity by 50%. Downregulation of SREBP activity by incubation with cholesterol+25-hydroxycholesterol had no effect on HL promoter activity. Overexpression of SREBP2, but not SREBP1, reduced HL promoter activity, which was effected mainly through the USF1 binding site at -307/-312. Oleate increased the nuclear abundance of USF1 protein 2.7 ± 0.6 fold, while USF1 levels were reduced by SREBP2 overexpression. We conclude that oleate increases HL gene expression via USF1. USF1 may be an additional fatty acid sensor in liver cells. Full article
(This article belongs to the Special Issue Foodomics 2009)
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Open AccessArticle Epidemiological Study of Rickettsial Infections in Patients with Hypertransaminemia in Madrid (Spain)
by , , , and
Int. J. Environ. Res. Public Health 2009, 6(10), 2526-2533; doi:10.3390/ijerph6102526
Received: 19 August 2009 / Accepted: 23 September 2009 / Published: 28 September 2009
Cited by 3 | Viewed by 4170 | PDF Full-text (254 KB) | HTML Full-text | XML Full-text
Abstract
A retrospective analysis was performed to detect anti-rickettsial antibodies in the serum of patients with hypertransaminemia of unknown etiology, and in that of healthy members of the general population of Madrid (Spain). Among 143 patients 16 (11.2%) were positive for anti-R. conorii
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A retrospective analysis was performed to detect anti-rickettsial antibodies in the serum of patients with hypertransaminemia of unknown etiology, and in that of healthy members of the general population of Madrid (Spain). Among 143 patients 16 (11.2%) were positive for anti-R. conorii IgG antibodies and 7% for R. typhi. PCR analysis was performed in patients with IgM antibodies. Among 143 healthy subjects from the general population, seven (4.9%) were positive for anti-R. conorii IgG antibodies, and 2.8% for R. typhi. These results show that anti-rickettsial antibodies are more commonly detected in patients with hypertransaminemia than in healthy people. Full article
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Open AccessArticle Chalcogenide Glass Optical Waveguides for Infrared Biosensing
by , , , , , , , , , , , , and
Sensors 2009, 9(9), 7398-7411; doi:10.3390/s90907398
Received: 8 July 2009 / Revised: 4 September 2009 / Accepted: 8 September 2009 / Published: 15 September 2009
Cited by 67 | Viewed by 7597 | PDF Full-text (609 KB) | HTML Full-text | XML Full-text
Abstract
Due to the remarkable properties of chalcogenide (Chg) glasses, Chg optical waveguides should play a significant role in the development of optical biosensors. This paper describes the fabrication and properties of chalcogenide fibres and planar waveguides. Using optical fibre transparent in the mid-infrared
[...] Read more.
Due to the remarkable properties of chalcogenide (Chg) glasses, Chg optical waveguides should play a significant role in the development of optical biosensors. This paper describes the fabrication and properties of chalcogenide fibres and planar waveguides. Using optical fibre transparent in the mid-infrared spectral range we have developed a biosensor that can collect information on whole metabolism alterations, rapidly and in situ. Thanks to this sensor it is possible to collect infrared spectra by remote spectroscopy, by simple contact with the sample. In this way, we tried to determine spectral modifications due, on the one hand, to cerebral metabolism alterations caused by a transient focal ischemia in the rat brain and, in the other hand, starvation in the mouse liver. We also applied a microdialysis method, a well known technique for in vivo brain metabolism studies, as reference. In the field of integrated microsensors, reactive ion etching was used to pattern rib waveguides between 2 and 300 μm wide. This technique was used to fabricate Y optical junctions for optical interconnections on chalcogenide amorphous films, which can potentially increase the sensitivity and stability of an optical micro-sensor. The first tests were also carried out to functionalise the Chg planar waveguides with the aim of using them as (bio)sensors. Full article
(This article belongs to the Special Issue State-of-the-Art Sensors Technology in Japan)
Open AccessArticle Relationship between Dietary Beef, Fat, and Pork and Alcoholic Cirrhosis
by
Int. J. Environ. Res. Public Health 2009, 6(9), 2417-2425; doi:10.3390/ijerph6092417
Received: 21 August 2009 / Accepted: 9 September 2009 / Published: 10 September 2009
Cited by 2 | Viewed by 6481 | PDF Full-text (148 KB) | HTML Full-text | XML Full-text
Abstract
Nanji and French [1] investigated the relationship between per-caput consumption of total fat, beef, and pork and for alcohol consumption and rates of mortality for cirrhosis for 16 countries for 1965. The present study reports significant and positive associations for 1996 and 2003
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Nanji and French [1] investigated the relationship between per-caput consumption of total fat, beef, and pork and for alcohol consumption and rates of mortality for cirrhosis for 16 countries for 1965. The present study reports significant and positive associations for 1996 and 2003 between the following: alcohol consumption and cirrhosis mortality, pork consumption and cirrhosis mortality, the product of alcohol and pork consumption and the product of alcohol and fat consumption. These supportive associations may represent a relationship between the risk of alcoholic cirrhosis and some heretofore unknown dietary or environmental factor related to conditions of pork or fat consumption. Limitations of the study design are discussed. Full article
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Open AccessReview HCV Animal Models: A Journey of More than 30 Years
by and
Viruses 2009, 1(2), 222-240; doi:10.3390/v1020222
Received: 12 June 2009 / Revised: 5 August 2009 / Accepted: 18 August 2009 / Published: 2 September 2009
Cited by 10 | Viewed by 4317 | PDF Full-text (218 KB) | HTML Full-text | XML Full-text
Abstract
In the 1970s and 1980s it became increasingly clear that blood transfusions could induce a form of chronic hepatitis that could not be ascribed to any of the viruses known to cause liver inflammation. In 1989, the hepatitis C virus (HCV) was discovered
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In the 1970s and 1980s it became increasingly clear that blood transfusions could induce a form of chronic hepatitis that could not be ascribed to any of the viruses known to cause liver inflammation. In 1989, the hepatitis C virus (HCV) was discovered and found to be the major causative agent of these infections. Because of its narrow ropism, the in vivo study of this virus was, especially in the early days, limited to the chimpanzee. In the past decade, several alternative animal models have been created. In this review we review these novel animal models and their contribution to our current understanding of the biology of HCV. Full article
(This article belongs to the Special Issue Hepatitis Viruses)
Open AccessArticle Synthesis and Antitumor Activity of Amino Acid Ester Derivatives Containing 5-Fluorouracil
by , , , , , and
Molecules 2009, 14(9), 3142-3152; doi:10.3390/molecules14093142
Received: 15 July 2009 / Revised: 18 August 2009 / Accepted: 20 August 2009 / Published: 25 August 2009
Cited by 19 | Viewed by 6316 | PDF Full-text (217 KB)
Abstract
A series of amino acid ester derivatives containing 5-fluorouracil were synthesized using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC•HCl) and N-hydroxybenzotriazole (HOBt) as a coupling agent. The structures of the products were assigned by NMR, MS, IR etc. The in vitro antitumor activity tests against leukaemia
[...] Read more.
A series of amino acid ester derivatives containing 5-fluorouracil were synthesized using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC•HCl) and N-hydroxybenzotriazole (HOBt) as a coupling agent. The structures of the products were assigned by NMR, MS, IR etc. The in vitro antitumor activity tests against leukaemia HL-60 and liver cancer BEL-7402 indicated that (R)-ethyl 2-(2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)-3-(4-hydroxyphenyl) propanoate showed more inhibitory effect against BEL-7402 than 5-FU. Full article
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Open AccessReview Hepatitis C Virus Infection: Molecular Pathways to Steatosis, Insulin Resistance and Oxidative Stress
by , and
Viruses 2009, 1(2), 126-143; doi:10.3390/v1020126
Received: 14 June 2009 / Revised: 27 July 2009 / Accepted: 29 July 2009 / Published: 11 August 2009
Cited by 34 | Viewed by 5225 | PDF Full-text (462 KB) | HTML Full-text | XML Full-text
Abstract
The persistent infection with hepatitis C virus is a major cause of chronic liver disease worldwide. However, the morbidity associated with hepatitis C virus widely varies and depends on several host-related cofactors, such as age, gender, alcohol consumption, body weight, and co-infections. The
[...] Read more.
The persistent infection with hepatitis C virus is a major cause of chronic liver disease worldwide. However, the morbidity associated with hepatitis C virus widely varies and depends on several host-related cofactors, such as age, gender, alcohol consumption, body weight, and co-infections. The objective of this review is to discuss three of these cofactors: steatosis, insulin resistance and oxidative stress. Although all may occur independently of HCV, a direct role of HCV infection in their pathogenesis has been reported. This review summarizes the current understanding and potential molecular pathways by which HCV contributes to their development. Full article
(This article belongs to the Special Issue Hepatitis Viruses)
Open AccessReview Selenium and the Methionine Sulfoxide Reductase System
by and
Molecules 2009, 14(7), 2337-2344; doi:10.3390/molecules14072337
Received: 12 June 2009 / Revised: 26 June 2009 / Accepted: 30 June 2009 / Published: 1 July 2009
Cited by 8 | Viewed by 9109 | PDF Full-text (54 KB) | HTML Full-text | XML Full-text
Abstract
Selenium is a chemical element participating in the synthesis of selenocysteine residues that play a pivotal role in the enzymatic activity efficiency of selenoproteines. The methionine sulfoxide reductase (Msr) system that reduces methionine sulfoxide (MetO) to methionine comprises the selenoprotein MsrB (MsrB1) and
[...] Read more.
Selenium is a chemical element participating in the synthesis of selenocysteine residues that play a pivotal role in the enzymatic activity efficiency of selenoproteines. The methionine sulfoxide reductase (Msr) system that reduces methionine sulfoxide (MetO) to methionine comprises the selenoprotein MsrB (MsrB1) and the non-selenoprotein MsrA, which reduce the R- and the S- forms of MetO, respectively. The effects of a selenium deficient (SD) diet, which was administrated to wild type (WT) and MsrA knockout mice (MsrA-/-), on the expression and function of Msr-related proteins are examined and discussed. Additionally, new data about the levels of selenium in brain, liver, and kidneys of WT and MsrA-/- mice are presented and discussed. Full article
(This article belongs to the Special Issue Selenium and Tellurium Chemistry)
Open AccessArticle Sesquiterpenes from Laurencia similis
by , , , , , and
Molecules 2009, 14(5), 1889-1897; doi:10.3390/molecules14051889
Received: 17 March 2009 / Revised: 21 April 2009 / Accepted: 27 April 2009 / Published: 20 May 2009
Cited by 13 | Viewed by 7015 | PDF Full-text (194 KB)
Abstract
One new sesquiterpene, (4E)-1-bromo-5-[(1'S*,3'R*)-3'-bromo-2',2'-dimethyl-6'-methylenecyclohexyl]-3-methylpent-4-ene-2,3-diol (1), and fifteen known sesquiterpenes, isopalisol (2), luzonensol (3), palisadin B (4), aplysistatin (5), palisadin A (6), 4-hydroxyl-palisudin C (7), 5-acetoxypalisadin B (8), 10-hydroxyaristolan-9-one (9), aristol-8-en-1-one (10), aristolan-9-en-1-one (11), aristolan-1(10)-en-9-one (12), aristolan-1(10)-en-9-ol (13),
[...] Read more.
One new sesquiterpene, (4E)-1-bromo-5-[(1'S*,3'R*)-3'-bromo-2',2'-dimethyl-6'-methylenecyclohexyl]-3-methylpent-4-ene-2,3-diol (1), and fifteen known sesquiterpenes, isopalisol (2), luzonensol (3), palisadin B (4), aplysistatin (5), palisadin A (6), 4-hydroxyl-palisudin C (7), 5-acetoxypalisadin B (8), 10-hydroxyaristolan-9-one (9), aristol-8-en-1-one (10), aristolan-9-en-1-one (11), aristolan-1(10)-en-9-one (12), aristolan-1(10)-en-9-ol (13), aristolan-1(10),8-diene (14), aristolan-1,9-diene (15) and aristofone (16), were isolated from a sample of marine red alga Laurencia similis. Their structures were established by detailed NMR spectroscopic analysis and comparison with literature data. Compounds 2-9, and 16 were isolated for the first time from this species. All these metabolites were submitted for a cytotoxicity assay against the tumor cell line BEL7402 (human liver adenocarcinoma), but all of them were found inactive (IC50 > 10 μg/mL). Full article
Open AccessArticle Protective Effects of Celery Juice in Treatments with Doxorubicin
by , , , and
Molecules 2009, 14(4), 1627-1638; doi:10.3390/molecules14041627
Received: 3 March 2009 / Revised: 14 April 2009 / Accepted: 23 April 2009 / Published: 24 April 2009
Cited by 11 | Viewed by 6019 | PDF Full-text (133 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this work was to investigate possible protective effect of celery juice in doxorubicin treatment. The following biochemical parameters were determined: content of reduced glutathione, activities of catalase, xanthine oxidase, glutathione peroxidase, peroxidase, and lipid peroxidation intensity in liver homogenate and
[...] Read more.
The aim of this work was to investigate possible protective effect of celery juice in doxorubicin treatment. The following biochemical parameters were determined: content of reduced glutathione, activities of catalase, xanthine oxidase, glutathione peroxidase, peroxidase, and lipid peroxidation intensity in liver homogenate and blood hemolysate. We examined influence of diluted pure celery leaves and roots juices and their combinations with doxorubicine on analyzed biochemical parameters. Celery roots and leaves juices influenced the examined biochemical parameters and showed protective effects when applied with doxorubicine. Full article
Open AccessArticle In Vitro Cytochrome P450 Formation of a Mono-Hydroxylated Metabolite of Zearalenone Exhibiting Estrogenic Activities: Possible Occurrence of This Metabolite in Vivo
by , , and
Int. J. Mol. Sci. 2009, 10(4), 1824-1837; doi:10.3390/ijms10041824
Received: 23 March 2009 / Accepted: 16 April 2009 / Published: 21 April 2009
Cited by 20 | Viewed by 8374 | PDF Full-text (227 KB) | HTML Full-text | XML Full-text
Abstract
The mycoestrogen zearalenone (ZEN), as well as its reduced metabolites, which belong to the endocrine disruptor bio-molecule family, are substrates for various enzymes involved in steroid metabolism. In addition to its reduction by the steroid dehydrogenase pathway, ZEN also interacts with hepatic detoxification
[...] Read more.
The mycoestrogen zearalenone (ZEN), as well as its reduced metabolites, which belong to the endocrine disruptor bio-molecule family, are substrates for various enzymes involved in steroid metabolism. In addition to its reduction by the steroid dehydrogenase pathway, ZEN also interacts with hepatic detoxification enzymes, which convert it into hydroxylated metabolites (OH-ZEN). Due to their structures to that of estradiol, ZEN and its derived metabolites bind to the estrogen receptors and are involved in endocrinal perturbations and are possibly associated with estrogen-dependent cancers. The primary aim of this present study was to identify the enzymatic cytochrome P450 isoforms responsible for the formation of the most abundant OH-ZEN. We thus studied its in vitro formation using hepatic microsomes in a range of animal model systems including man. OH-ZEN was also recovered in liver and urine of rats treated orally with ZEN. Finally we compared the activity of ZEN and its active metabolites (α-ZAL and OH-ZEN) on estrogen receptors using HeLa ER-α and ER-β reporter cell lines as reporters. OH-ZEN estrogenic activities were revealed to be limited and not as significant as those of ZEN or α-ZAL. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
Open AccessAbstract In vitro Evaluation of the Hepatotoxic Potential of Aqueous and Methanolic Extracts of Myricaria longifolia
by , , , and
Sci. Pharm. 2009, 77(Posters (PO)), 268; doi:10.3797/scipharm.oephg.21.PO-69 (registering DOI)
Received: 16 April 2009 / Accepted: 16 April 2009 / Published: 16 April 2009
Viewed by 33 | PDF Full-text (236 KB)
Abstract
In a previous study aqueous extracts of several plant species frequently used in the traditional Mongolian therapy of liver disorders have been analysed for potential genotoxic or cytotoxic properties in the primary rat hepatocyte assay with or without proliferative stimulation by the epidermal
[...] Read more.
In a previous study aqueous extracts of several plant species frequently used in the traditional Mongolian therapy of liver disorders have been analysed for potential genotoxic or cytotoxic properties in the primary rat hepatocyte assay with or without proliferative stimulation by the epidermal growth factor EGF. Full article
Open AccessAbstract Expression of Sulfotransferases and Sulfatases in Human Breast Cancer: Impact on Resveratrol Metabolism
by , , , and
Sci. Pharm. 2009, 77(Short Lectures (SL)), 197; doi:10.3797/scipharm.oephg.21.SL-30 (registering DOI)
Received: 16 April 2009 / Accepted: 16 April 2009 / Published: 16 April 2009
Viewed by 53 | PDF Full-text (199 KB)
Abstract
Resveratrol is a naturally occurring anticancer compound present in grapes and wine that undergoes pronounced metabolism in human intestine and liver. In order to determine whether resveratrol is also biotransformed in human breast carcinoma, metabolism experiments were conducted in breast tumor and adjacent
[...] Read more.
Resveratrol is a naturally occurring anticancer compound present in grapes and wine that undergoes pronounced metabolism in human intestine and liver. In order to determine whether resveratrol is also biotransformed in human breast carcinoma, metabolism experiments were conducted in breast tumor and adjacent non-tumorous specimens from 13 patients. Resveratrol was metabolized in cytosolic tissue fractions to resveratrol-3-O-sulfate: the formation rates were up to 33.5-fold higher in cancer samples than in peritumoral tissue. Full article
Open AccessArticle Mycotoxin Detection in Human Samples from Patients Exposed to Environmental Molds
by , , and
Int. J. Mol. Sci. 2009, 10(4), 1465-1475; doi:10.3390/ijms10041465
Received: 4 February 2009 / Revised: 13 March 2009 / Accepted: 27 March 2009 / Published: 1 April 2009
Cited by 34 | Viewed by 10105 | PDF Full-text (85 KB) | HTML Full-text | XML Full-text
Abstract
The goal of this study was to determine if selected mycotoxins (trichothecenes, aflatoxins, and ochratoxins) could be extracted and identified in human tissue and body fluids from patients exposed to toxin producing molds in their environment. Human urine and methanol extracted tissues and
[...] Read more.
The goal of this study was to determine if selected mycotoxins (trichothecenes, aflatoxins, and ochratoxins) could be extracted and identified in human tissue and body fluids from patients exposed to toxin producing molds in their environment. Human urine and methanol extracted tissues and sputum were examined. Trichothecenes were tested using competitive ELISA techniques. Aflatoxins B1, B2, G1, and G2, and ochratoxin A were tested by using immunoaffinity columns and fluorometry. Test sensitivity and specificity were determined. Levels of detection for the various mycotoxins varied from 0.2 ppb for trichothecenes, 1.0 ppb for aflatoxins, and 2.0 ppb for ochratoxins. Trichothecene levels varied in urine, sputum, and tissue biopsies (lung, liver, brain) from undetectable (<0.2 ppb) to levels up to 18 ppb. Aflatoxin levels from the same types of tissues varied from 1.0 to 5.0 ppb. Ochratoxins isolated in the same type of tissues varied from 2.0 ppb to > 10.0 ppb. Negative control patients had no detectable mycotoxins in their tissues or fluids. These data show that mycotoxins can be detected in body fluids and human tissue from patients exposed to mycotoxin producing molds in the environment, and demonstrate which human tissues or fluids are the most likely to yield positive results. Full article
(This article belongs to the Special Issue Mycotoxins: Mechanisms of Toxicological Activity - Treatment and Prevention)
Open AccessArticle Changes in Metallothionein Level in Rat Hepatic Tissue after Administration of Natural Mouldy Wheat
by , , , and
Int. J. Mol. Sci. 2009, 10(3), 1138-1160; doi:10.3390/ijms10031138
Received: 3 January 2009 / Revised: 28 February 2009 / Accepted: 9 March 2009 / Published: 12 March 2009
Cited by 15 | Viewed by 7087 | PDF Full-text (644 KB) | HTML Full-text | XML Full-text
Abstract
Mycotoxins are secondary metabolites produced by microfungi that are capable of causing disease and death in humans and other animals. This work was aimed at investigation of influence of mouldy wheat contaminated by pathogenic fungi producing mycotoxins on metallothionein levels in hepatic tissue
[...] Read more.
Mycotoxins are secondary metabolites produced by microfungi that are capable of causing disease and death in humans and other animals. This work was aimed at investigation of influence of mouldy wheat contaminated by pathogenic fungi producing mycotoxins on metallothionein levels in hepatic tissue of rats. The rats were administrating feed mixtures with different contents of vitamins or naturally mouldy wheat for 28 days. It was found that the wheat contained deoxynivalenol (80 ± 5 µg per kg of mouldy wheat), zearalenone (56 ± 3 µg/kg), T2-toxin (20 ± 2 µg/kg) and aflatoxins as a sum of B1, B2, G1 and G2 (3.9 ± 0.2 µg/kg). Rats were fed diets containing 0, 33, 66 and 100% naturally moulded wheat. Control group 0, 33, 66 and 100% contained vitamins according to Nutrient Requirements of Rats (NRC). Other four groups (control group with vitamins, vit33, vit66 and vit100%) were fed on the same levels of mouldy wheat, also vitamins at levels 100% higher than the previous mixtures. We determined weight, feed conversion and performed dissection to observe pathological processes. Changes between control group and experimental groups exposed to influence of mouldy wheat and experimental groups supplemented by higher concentration of vitamins and mouldy wheat were not observed. Livers were sampled and did not demonstrate significant changes in morphology compared to control either. In the following experiments the levels of metallothionein as a marker of oxidative stress was determined. We observed a quite surprising trend in metallothionein levels in animals supplemented with increased concentration of vitamins. Its level enhanced with increasing content of mouldy wheat. It was possible to determine a statistically significant decline (p<0.05) between control group and groups of animals fed with 33, 66 and 100% mouldy wheat. It is likely that some mycotoxins presented in mouldy wheat are able to block the mechanism of metallothionein synthesis. Full article
(This article belongs to the Special Issue Mycotoxins: Mechanisms of Toxicological Activity - Treatment and Prevention)
Open AccessReview Biomarkers of Induced Active and Passive Smoking Damage
by and
Int. J. Environ. Res. Public Health 2009, 6(3), 874-888; doi:10.3390/ijerph6030874
Received: 23 December 2008 / Accepted: 20 February 2009 / Published: 26 February 2009
Cited by 30 | Viewed by 5300 | PDF Full-text (293 KB) | HTML Full-text | XML Full-text
Abstract
In addition to thewell-known link between smoking and lung cancer, large epidemiological studies have shown a relationship between smoking and cancers of the nose, oral cavity, oropharynx, larynx, esophagus, pancreas, bladder, kidney, stomach, liver, colon and cervix, as well as myeloid leukemia. Epidemiological
[...] Read more.
In addition to thewell-known link between smoking and lung cancer, large epidemiological studies have shown a relationship between smoking and cancers of the nose, oral cavity, oropharynx, larynx, esophagus, pancreas, bladder, kidney, stomach, liver, colon and cervix, as well as myeloid leukemia. Epidemiological evidence has reported a direct link between exposure of non-smokers to environmental tobacco smoke and disease, most notably, lung cancer. Much evidence demonstrates that carcinogenic-DNA adducts are useful markers of tobacco smoke exposure, providing an integrated measurement of carcinogen intake, metabolic activation, and delivery to the DNA in target tissues. Monitoring accessible surrogate tissues, such as white blood cells or bronchoalveolar lavage (BAL) cells, also provides a means of investigating passive and active tobacco exposure in healthy individuals and cancer patients. Levels of DNA adducts measured in many tissues of smokers are significantly higher than in non-smokers. While some studies have demonstrated an association between carcinogenic DNA adducts and cancer in current smokers, no association has been observed in ex or never smokers. The role of genetic susceptibility in the development of smoking related-cancer is essential. In order to establish whether smoking-related DNA adducts are biomarkers of tobacco smoke exposure and/or its carcinogenic activity we summarized all data that associated tobacco smoke exposure and smoking-related DNA adducts both in controls and/or in cancer cases and studies where the effect of genetic polymorphisms involved in the activation and deactivation of carcinogens were also evaluated. In the future we hope we will be able to screen for lung cancer susceptibility by using specific biomarkers and that subjects of compared groups can be stratified for multiple potential modulators of biomarkers, taking into account various confounding factors. Full article
(This article belongs to the Special Issue Tobacco Smoking and Public Health)
Open AccessArticle Investigation on the Protective Effect of α-Mannan against the DNA Damage Induced by Aflatoxin B1 in Mouse Hepatocytes
by , , , and
Int. J. Mol. Sci. 2009, 10(2), 395-406; doi:10.3390/ijms10020395
Received: 21 November 2008 / Revised: 5 January 2009 / Accepted: 6 January 2009 / Published: 1 February 2009
Cited by 8 | Viewed by 8369 | PDF Full-text (363 KB) | HTML Full-text | XML Full-text
Abstract
Aflatoxin B1 is a contaminant of agricultural and dairy products that can be related to mutagenic and carcinogenic effects. In this report we explore the capacity of α-mannan (Man) to reduce the DNA damage induced by AFB1 in mouse hepatocytes. For
[...] Read more.
Aflatoxin B1 is a contaminant of agricultural and dairy products that can be related to mutagenic and carcinogenic effects. In this report we explore the capacity of α-mannan (Man) to reduce the DNA damage induced by AFB1 in mouse hepatocytes. For this purpose we applied the comet assay to groups of animals which were first administered Man (100, 400 and 700 mg/kg, respectively) and 20 min later 1.0 mg/kg of AFB1. Liver cells were obtained at 4, 10, and 16 h after the chemical administration and examined. The results showed no protection of the damage induced by AFB1 with the low dose of the polysaccharide, but they did reveal antigenotoxic activity exerted by the two high doses. In addition, we induced a co-crystallization between both compounds, determined their fusion points and analyzed the molecules by UV spectroscopy. The obtained data suggested the formation of a supramolecular complex between AFB1 and Man. Full article
(This article belongs to the Special Issue Mycotoxins: Mechanisms of Toxicological Activity - Treatment and Prevention)
Open AccessReview Biological and Pharmacological Activities of Squalene and Related Compounds: Potential Uses in Cosmetic Dermatology
by , and
Molecules 2009, 14(1), 540-554; doi:10.3390/molecules14010540
Received: 8 January 2009 / Revised: 19 January 2009 / Accepted: 21 January 2009 / Published: 23 January 2009
Cited by 101 | Viewed by 15877 | PDF Full-text (466 KB) | HTML Full-text | XML Full-text
Abstract
Squalene is a triterpene that is an intermediate in the cholesterol biosynthesis pathway. It was so named because of its occurrence in shark liver oil, which contains large quantities and is considered its richest source. However, it is widely distributed in nature, with
[...] Read more.
Squalene is a triterpene that is an intermediate in the cholesterol biosynthesis pathway. It was so named because of its occurrence in shark liver oil, which contains large quantities and is considered its richest source. However, it is widely distributed in nature, with reasonable amounts found in olive oil, palm oil, wheat-germ oil, amaranth oil, and rice bran oil. Squalene, the main component of skin surface polyunsaturated lipids, shows some advantages for the skin as an emollient and antioxidant, and for hydration and its antitumor activities. It is also used as a material in topically applied vehicles such as lipid emulsions and nanostructured lipid carriers (NLCs). Substances related to squalene, including β-carotene, coenzyme Q10 (ubiquinone) and vitamins A, E, and K, are also included in this review article to introduce their benefits to skin physiology. We summarize investigations performed in previous reports from both in vitro and in vivo models. Full article
(This article belongs to the Special Issue Triterpenes and Triterpenoids)
Open AccessArticle Ethyl Carbamate in Alcoholic Beverages from Mexico (Tequila, Mezcal, Bacanora, Sotol) and Guatemala (Cuxa): Market Survey and Risk Assessment
by , , , and
Int. J. Environ. Res. Public Health 2009, 6(1), 349-360; doi:10.3390/ijerph6010349
Received: 19 December 2008 / Accepted: 16 January 2009 / Published: 20 January 2009
Cited by 30 | Viewed by 11678 | PDF Full-text (279 KB) | HTML Full-text | XML Full-text
Abstract
Ethyl carbamate (EC) is a recognized genotoxic carcinogen, with widespread occurrence in fermented foods and beverages. No data on its occurrence in alcoholic beverages from Mexico or Central America is available. Samples of agave spirits including tequila, mezcal, bacanora and sotol (n=110), and
[...] Read more.
Ethyl carbamate (EC) is a recognized genotoxic carcinogen, with widespread occurrence in fermented foods and beverages. No data on its occurrence in alcoholic beverages from Mexico or Central America is available. Samples of agave spirits including tequila, mezcal, bacanora and sotol (n=110), and of the sugarcane spirit cuxa (n=16) were purchased in Mexico and Guatemala, respectively, and analyzed for EC. The incidence of EC contamination was higher in Mexico than in Guatemala, however, concentrations were below international guideline levels (<0.15 mg/L). Risk assessment found the Margin of Exposure (MOE) in line with that of European spirits. It is therefore unlikely that EC plays a role in high rates of liver cirrhosis reported in Mexico. Full article
(This article belongs to the Special Issue Environmental Research on Alcohol: Public Health Perspectives)
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Open AccessReview Tetrodotoxin – Distribution and Accumulation in Aquatic Organisms, and Cases of Human Intoxication
by and
Mar. Drugs 2008, 6(2), 220-242; doi:10.3390/md6020220
Received: 23 December 2007 / Revised: 24 March 2008 / Accepted: 8 April 2008 / Published: 28 May 2008
Cited by 139 | Viewed by 10179 | PDF Full-text (423 KB) | HTML Full-text | XML Full-text
Abstract
Many pufferfish of the family Tetraodontidae possess a potent neurotoxin, tetrodotoxin (TTX). In marine pufferfish species, toxicity is generally high in the liver and ovary, whereas in brackish water and freshwater species, toxicity is higher in the skin. In 1964, the toxin of
[...] Read more.
Many pufferfish of the family Tetraodontidae possess a potent neurotoxin, tetrodotoxin (TTX). In marine pufferfish species, toxicity is generally high in the liver and ovary, whereas in brackish water and freshwater species, toxicity is higher in the skin. In 1964, the toxin of the California newt was identified as TTX as well, and since then TTX has been detected in a variety of other organisms. TTX is produced primarily by marine bacteria, and pufferfish accumulate TTX via the food chain that begins with these bacteria. Consequently, pufferfish become non-toxic when they are fed TTX-free diets in an environment in which the invasion of TTX-bearing organisms is completely shut off. Although some researchers claim that the TTX of amphibians is endogenous, we believe that it also has an exogenous origin, i.e., from organisms consumed as food. TTX-bearing animals are equipped with a high tolerance to TTX, and thus retain or accumulate TTX possibly as a biologic defense substance. There have been many cases of human intoxication due to the ingestion of TTX-bearing pufferfish, mainly in Japan, China, and Taiwan, and several victims have died. Several cases of TTX intoxication due to the ingestion of small gastropods, including some lethal cases, were recently reported in China and Taiwan, revealing a serious public health issue. Full article
(This article belongs to the Special Issue Marine Toxins)
Open AccessArticle Utilizing of Adsorptive Transfer Stripping Technique Brdicka Reaction for Determination of Metallothioneins Level in Melanoma Cells, Blood Serum and Tissues
by , , , , , , , , and
Sensors 2008, 8(5), 3106-3122; doi:10.3390/s8053106
Received: 22 April 2008 / Accepted: 9 May 2008 / Published: 10 May 2008
Cited by 38 | Viewed by 5550 | PDF Full-text (185 KB) | HTML Full-text | XML Full-text
Abstract
In the paper we utilized the adsorptive transfer stripping differential pulse voltammetry Brdicka reaction for the determination of metallothioneins (MT) in melanoma cells, animal melanoma tissues (MeLiM miniature pig) and blood serum of patients with malignant melanoma. Primarily we attempted to investigate the
[...] Read more.
In the paper we utilized the adsorptive transfer stripping differential pulse voltammetry Brdicka reaction for the determination of metallothioneins (MT) in melanoma cells, animal melanoma tissues (MeLiM miniature pig) and blood serum of patients with malignant melanoma. Primarily we attempted to investigate the influence of dilution of real sample on MT electrochemical response. Dilution of samples of 1 000 times was chosen the most suitable for determination of MT level in biological samples. Then we quantified the MT level in the melanoma cells, the animal melanoma tissues and the blood serum samples. The MT content in the cells varied within the range from 4.2 to 11.2 μM. At animal melanoma tissues (melanomas localized on abdomen, back limb and dorsum) the highest content of MT was determined in the tumour sampled on the back of the animal and was nearly 500 μg of MTs per gram of a tissue. We also quantified content of MT in metastases, which was found in liver, spleen and lymph nodes. Moreover the average MT level in the blood serum samples from patients with melanoma was 3.0 ± 0.8 μM. MT levels determined at melanoma samples were significantly (p < 0.05) higher compared to control ones at cells, tissues and blood serum. Full article
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