Search

Studies of changes in fatty acids in response to environmental temperature changes have been conducted in many species, particularly mammals. However, few studies have considered aquatic invertebrates, even though they are particularly vulnerable to changes in environmental temperature. In this review, we summarize the process by which animals synthesize common fatty acids and point out differences between the fatty acid profiles of vertebrates and those of aquatic invertebrates. Unlike vertebrates, some aquatic invertebrates can directly synthesize polyunsaturated fatty acids (PUFAs), which can be used to respond to temperature changes. Various studies have shown that aquatic invertebrates increase the degree of saturation in their fatty acids through an increase in saturated fatty acid production or a decrease in PUFAs as the temperature increases. In addition, we summarize recent studies that have examined the complex effects of temperature and combinational stressors to determine whether the degree of saturation in aquatic invertebrates is influenced by other factors. The combined effects of carbon dioxide partial pressure, food quality, starvation, salinity, and chemical exposures have been confirmed, and fatty acid profile changes in response to high temperature were greater than those from combinational stressors., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Despite the extensive usage of synthetic musk compounds (SMCs) and siloxanes in various personal care products (PCPs), trophic magnification of such chemicals in aquatic environments remains unexplored. In June and September 2020, eleven SMCs and nineteen siloxanes were measured in water, sediments, and biota. Samples were collected from two sites where levels were expected to be influenced by the distance from the wastewater treatment plant (WWTP) in the Geum River, Republic of Korea, were expected. High concentrations of SMCs and siloxanes entered through WWTP were measured in water, sediment, and biota at the both sites and both seasons. The δ 15 N of amino acids provided a high-resolution food web and accurate trophic position (TP), which is an important factor for determining the trophic magnification factor (TMF). Among 24 TMFs, 19 of them were <1, ranging 0.7-0.8 for 1,3,4,6,7,8‑hexahydro‑4,6,6,7,8,8‑hexamethyl‑cyclopenta‑γ‑2‑benzopyran (HHCB), 0.6-0.8 for 6-Acetyl-1,1,2,4,4,7-hexamethyltetralin (AHTN), 0.7-0.8 for 4-tert-Butyl-3,5-dinitro-2,6-dimethylacetophenone (MK), 0.7-0.9 for octamethylcyclotetrasiloxane (D4), 0.1-0.4 for decamethylcyclopentasiloxane (D5), and 0.04-0.8 for dodecamethylcyclohexasiloxane (D6), and the remaining ones including HHCB, AHTN, MK, and D4 showed values close to 1 or slightly higher (TMF range: 1.0-2.3) indicating no or a little trophic magnification. The TMFs of these compounds were constant across sites and seasons. The TMF values of PCPs might be affected by species specificity and food web structure rather than by chemical properties such as log K ow , which describes a wide range of TMF values in various environments. This study presents valuable implications for assessing risk and managing environmental fate and trophic transfer of SMCs and siloxanes in freshwater environments., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Low-temperature exposure prolongs lifespans and changes lipid metabolism but the relationship between longevity and lipids is largely unknown. Here, we examine the relationship between longevity and lipid metabolism at low temperatures (20 °C and 15 °C) compared with a 25 °C control. Life parameters, fatty acid composition, and transcriptome changes were analyzed in the monogonont rotifer Brachionus koreanus. In vivo life-parameter data indicate that lifespan and fecundity exhibit opposite correlations at low temperatures. The amount of total fatty acids decreased significantly at low temperatures but areas stained with Nile red increased at 15 °C compared with the control. From RNA-seq-based transcriptional analysis, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-enrichment analysis were conducted. GO analysis shows that telomeres were positively regulated at low temperatures. KEGG pathway-enrichment results indicate that gene expression involved in lipid metabolism was activated with increased glycerol and/or choline synthesis at low temperatures. We suggest that reduced reproductive rates are associated with a decrease of lecithin, which is involved in the conversion of glycerol to triacylglycerol in response to low temperatures by lowering the temperature of body fluid., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The trophic magnification of persistent organic pollutants (POPs), which is the relationship between POP concentration and the trophic position (TPs) of an organism, is considered an important factor for prioritizing chemicals of concern in the environment. Organismal TPs are typically based on nitrogen isotope ratios of bulk tissue (δ 15 N bulk ). In this study, nitrogen isotope ratios of amino acids (δ 15 N AAs ), a more precise approach for TP estimation (TP AAs ), was applied and compared with estimations of TP based on δ 15 N bulk (TP bulk ) in marine organisms living in Masan Bay, South Korea. Compound-specific isotope analysis of the amino acids (CSIA-AAs) in fish samples allows us to calculate robust TPs by correcting the variation in baseline isotope values with use of the δ 15 N bulk technique. In a benthic food chain, this approach reveals more significant magnification trends for POPs [polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs)] than those revealed by analysis of the relationship between TP bulk and POPs. The trophic magnification factors (TMF) associated with TP AAs were significant for some POPs, especially pp'-DDD and chlordane. The results presented in this study suggest that TP calculations based on δ 15 N AAs are an effective tool for characterizing trophic magnification trends related to the fates of various pollutants., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

To determine distributions, bioaccumulation, and trophic transfer of freshwater cyanobacterial toxins such as microcystins (MCs), surface water, suspended solids, sediments, and coastal organisms were collected from seven stations in inner and outer regions of the estuary dam in the Geum River Estuary in June and July 2017. Concentrations of MC variants (MC-LR, -RR, and -YR) in the multimedia samples were analyzed using a HPLC-MS/MS. Trophic position (TP) of organisms (fish, bivalve, gastropod, decapod, and polychaete) was determined by nitrogen stable isotope analyses of both bulk tissues and amino acids. From July to August 2017, great concentrations of MCs were detected in discharged freshwater ranging from 0.4 to 75 μg L -1 . Considerable amounts of MCs are delivered to the Geum River Estuary in summer season. MCs spread far away as dissolved phases (18.7-49.5 ng L -1 ) in July when large amount of freshwater was discharged during the rainy season. Concentrations of MCs in marine organisms varied among species, ranging from 40 to 870 ng g -1 dw. Bioaccumulated MCs tend to decrease with increasing TP of organisms, suggesting that MCs are biodiluted through the marine food web. Compound-specific isotope analysis (nitrogen of amino acids) provides more reliable TPs compared with those by bulk isotope analysis in a closed estuary (such as the Geum River Estuary) with large fluctuations in the isotope ratio of primary producers., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In this study, surface water samples were collected at sites located in the lowest reaches of closed (Geum) (i.e. with an estuary dam at the river mouth) and open (Seomjin) estuary systems between May 2016 and May 2018. We analyzed concentrations and stable isotopes of particulate organic carbon (POC) and dissolved organic carbon (DOC) to assess OC sources, to estimate fluxes of riverine OC, and to assess some of the factors driving OC exports in these two contrasting Korean estuary systems. Our geochemical results suggest that the contribution of the phytoplankton-derived POC to the total POC pool was larger in the Geum River than in the Seomjin River. Notably, a heavy riverine algae bloom occurred in the Geum River in August 2016, resulting in a high carbon isotopic composition (-19.4‰) together with low POC/PN ratio (<10) and POC/Chl-a ratio (<100). In contrast, potential DOC sources in both the Geum River and the Seomjin River were a mixture of C 3 -derived forest soils and cropland organic matter. During the study period, the catchment area-normalized fluxes of POC and DOC were 0.40 × 10 -3  tC/km 2 /yr and 6.5 × 10 -2  tC/km 2 /yr in the Geum River and 5.2 × 10 -4  tC/km 2 /yr and 8.6 × 10 -4  tC/km 2 /yr in the Seomjin River, respectively. It appears that the POC flux was more weakly associated with the water discharge in the Geum River than in the Seomjin River, but the DOC fluxes were in general controlled by the water discharges in both rivers. Accordingly, the estuary dam of the Geum River might be one of the most strongly influencing factors on seasonal patterns in POC fluxes into the adjacent coastal seas, strongly modifying water residence times and thus biogeochemical processes., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study utilized effect-directed analysis (EDA) combined with full-scan screening analysis (FSA) to identify aryl hydrocarbon receptor (AhR)-active compounds in sediments of inland creeks flowing into Lake Sihwa, South Korea. The specific objectives were to (i) investigate the major AhR-active fractions of organic extracts of sediments by using H4IIE-luc in vitro bioassay (4 h and 72 h exposures), (ii) quantify known AhR agonists, such as polycyclic aromatic hydrocarbons (PAHs) and styrene oligomers (SOs), (iii) identify unknown AhR agonists by use of gas chromatography-quadrupole time-of-flight mass spectrometry (GC-QTOFMS), and (iv) determine contributions of AhR agonists to total potencies measured by use of the bioassay. FSA was conducted on fractions F2.6 and F2.7 (aromatics with log K ow 5-7) in extracts of sediment from Siheung Creek (industrial area). Those fractions exhibited significant AhR-mediated potency as well as relatively great concentrations of PAHs and SOs. FSA detected 461 and 449 compounds in F2.6 and F2.7, respectively. Of these, five tentative candidates of AhR agonist were selected based on NIST library matching, aromatic structures and numbers of rings, and available standards. Benz[b]anthracene, 11H-benzo[a]fluorene, and 4,5-methanochrysene exhibited significant AhR-mediated potency in the H4IIE-luc bioassay, and relative potencies of these compounds were determined. Potency balance analysis demonstrated that these three newly identified AhR agonists explained 1.1% to 67% of total induced AhR-mediated potencies of samples, which were particularly great for industrial sediments. Follow-up studies on sources and ecotoxicological effects of these compounds in coastal environments would be required., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Hepatitis B virus (HBV) DNA levels are used to predict the response to therapy, determine therapy initiation, monitor resistance to therapy, and establish treatment success., Objective: To verify the performance of the cobas HBV test using the cobas 4800 system for HBV DNA quantification and to compare the HBV DNA quantification ability between the cobas HBV test and COBAS AmpliPrep/COBAS TaqMan HBV version 2.0 (CAP/CTM v2.0)., Study Design: The precision, linearity, and limit of detection of the cobas HBV test were evaluated using the 4th World Health Organization International Standard material and plasma samples. Clinical samples that yielded quantitative results using the CAP/CTM v2.0 and cobas HBV tests were subjected to correlational analysis., Results: Three hundred forty-nine samples were subjected to correlational analysis, among which 114 samples showed results above the lower limit of quantification. Comparable results were obtained ([cobas HBV test] = 1.038 × [CAP/CTM v2.0]-0.173, r = 0.914) in 114 samples, which yielded values above the lower limit of quantification. The results for 86.8% of the samples obtained using the cobas HBV test were within 0.5 log 10 IU/mL of the CAP/CTM v2.0 results. The total precision values against the low and high positive controls were 1.4% (mean level: 2.25 log 10 IU/mL) and 3.2% (mean level: 6.23 log 10 IU/mL), respectively. The cobas HBV test demonstrated linearity (1.15-6.75 log 10 IU/mL, y = 0.95 × 6 + 0.17, r 2  = 0.994)., Conclusion: The cobas HBV test showed good correlation with CAP/CTM v2.0, and had good precision and an acceptable limit of detection. The cobas HBV test using the cobas 4800 is a reliable method for quantifying HBV DNA levels in the clinical setting., (Copyright © 2018. Published by Elsevier B.V.)

Salinity is a critical key abiotic factor affecting biological processes such as lipid metabolism, yet the relationship between salinity and lipid metabolism has not been studied in the rotifer. To understand the effects of salinity on the monogonont rotifer B. koreanus, we examined high saline (25 and 35psu) conditions compared to the control (15psu). In vivo life cycle parameters (e.g. cumulative offspring and life span) were observed in response to 25 and 35psu compared to 15psu. In addition, to investigate whether high salinity induces oxidative stress, the level of reactive oxygen species (ROS) and glutathione S-transferase activity (GST) were measured in a salinity- (15, 25, and 35psu; 24h) and time-dependent manner (3, 6, 12, 24h; 35psu). Furthermore composition of fatty acid (FA) and lipid metabolism-related genes (e.g. elongases and desaturases) were examined in response to different salinity conditions. As a result, retardation in cumulative offspring and significant increase in life span were demonstrated in the 35psu treatment group compared to the control (15psu). Furthermore, ROS level and GST activity have both demonstrated a significant increase (P<0.05) in the 35psu treatment. In general, the quantity of FA and mRNA expression of the lipid metabolism-related genes was significantly decreased (P<0.05) in response to high saline condition with exceptions for both GST-S4 and S5 demonstrated a significant increase in their mRNA expression. This study demonstrates that high salinity induces oxidative stress, leading to a negative impact on lipid metabolism in the monogonont rotifer, B. koreanus., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Metformin reduces body weight by decreasing food intake in humans and animals. However, the brain regions involved in metformin-induced anorexia remain unclear. Therefore, we investigated c-Fos expression (FOS), a marker of neuronal activity, in the appetite-regulating brain regions after oral administration of metformin (PO, 300mg/kg daily for 1 or 3days) or vehicle. The body weight and food intake decreased in mice treated with metformin for 3days (RM group) and mice that had the same amount of food as the RM group (Pair-fed group; PF) compared to the control group. FOS expression levels increased in the paraventricular nucleus, area postrema, and central amygdala of mice administered an acute single dose of metformin (SM group) compared to the control mice. In the nucleus tractus solitarius, the FOS expression levels increased in both the SM and RM groups compared to the control group. The FOS expression levels also increased in the nucleus accumbens of the RM group compared to other groups. The FOS expression levels decreased in the ventromedial hypothalamic nucleus in the PF group, but not the RM group, compared to the control group, suggesting a potential hypothalamic area involvement for metformin-induced anorexia. These results suggest that both the hypothalamic and extra-hypothalamic regions are associated with metformin-induced anorexia, which is dependent on metformin treatment duration., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Ultraviolet B (UV-B) radiation presents an environmental hazard to aquatic organisms. To understand the molecular responses of the intertidal copepod Tigriopus japonicus to UV-B radiation, we measured the acute toxicity response to 96 h of UV-B radiation, and we also assessed the intracellular reactive oxygen species (ROS) levels, glutathione (GSH) content, and antioxidant enzyme (GST, GR, GPx, and SOD) activities after 24 h of exposure to UV-B with LD50 and half LD50 values. Also, expression patterns of p53 and hsp gene families with phosphorylation of p38 MAPK were investigated in UV-B-exposed copepods. We found that the ROS level, GSH content, and antioxidant enzyme activity levels were increased with the transcriptional upregulation of antioxidant-related genes, indicating that UV-B induces oxidative stress by generating ROS and stimulating antioxidant enzymatic activity as a defense mechanism. Additionally, we found that p53 expression was significantly increased after UV-B irradiation due to increases in the phosphorylation of the stress-responsive p38 MAPK, indicating that UV-B may be responsible for inducing DNA damage in T. japonicus. Of the hsp family genes, transcriptional levels of hsp20, hsp20.7, hsp70, and hsp90 were elevated in response to a low dose of UV-B radiation (9 kJ m(-2)), suggesting that these hsp genes may be involved in cellular protection against UV-B radiation. In this paper, we performed a pathway-oriented mechanistic analysis in response to UV-B radiation, and this analysis provides a better understanding of the effects of UV-B in the intertidal benthic copepod T. japonicus., (Copyright © 2014 Elsevier Inc. All rights reserved.)

To evaluate the effects of UV radiation on the reproductive physiology and macromolecules in marine zooplankton, several doses of UV radiation were used to treat the copepod Paracyclopina nana, and we analyzed in vivo endpoints of their life cycle such as mortality and reproductive parameters with in vitro biochemical biomarkers such as reactive oxygen species (ROS), the modulated enzyme activity of glutathione S-transferase (GST) and superoxide dismutase (SOD), and the production of a byproduct of peroxidation (e.g. malonedialdehyde, MDA). After UV radiation, the survival rate of P. nana was significantly reduced. Also, egg sac damage and a reduction in the hatching rate of offspring were observed in UV-irradiated ovigerous females. According to the assessed biochemical parameters, we found dose-dependent increases in ROS levels and high levels of the lipid peroxidation decomposition product by 2 kJ m(-2), implying that P. nana was under off-balanced status by oxidative stress-mediated cellular damage. Antioxidant enzyme activities of GST and SOD increased over different doses of UV radiation. To measure UV-induced lipid peroxidation, we found a slight reduction in the composition of essential fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These findings indicate that UV radiation can induce oxidative stress-triggered lipid peroxidation with modulation of antioxidant enzyme activity, leading to a significant effect on mortality and reproductive physiology (e.g. fecundity). These results demonstrate the involvement of UV radiation on essential fatty acids and its susceptibility to UV radiation in the copepod P. nana compared to other species., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To evaluate and report the results of a 3-year study investigating argon laser photoablation of superficial conjunctival nevus., Design: Retrospective, interventional case series., Methods: The medical charts of patients referred to our clinic for the removal of a conjunctival nevus were reviewed. Argon laser photoablation of superficial conjunctival nevi was performed for 230 patients during the period from March 2006 to February 2009. The clinical course, complications, and recurrence rates were evaluated., Results: The mean follow-up period was 71.29 ± 19.51 months (range, 36-100 months). The horizontal and vertical diameters of conjunctival nevi were 4.53 ± 1.85 mm and 3.41 ± 1.62 mm, respectively. Most nevi were faintly pigmented and located on the nasal bulbar conjunctiva. The argon laser spot size was 200 μm; its duration was 0.1 second; and the power was 321.50 ± 9.23 mW. One session was required to completely remove the nevus in 212 eyes (81%). The total number of laser spots that were required to remove 1 nevus was 107.83 ± 33.68 (range, 53-172) for cases in which the horizontal and vertical diameters were <4 mm. In all cases, the laser procedure resulted in complete removal of the conjunctival nevus. There were no significant complications, such as infection, corneal damage, or permanent injection., Conclusions: Argon laser photoablation could be a safe and effective treatment for benign superficial conjunctival pigmentation. This method is especially helpful for large conjunctival nevi, for which surgical excision would be impossible., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Metformin is widely used to treat obese diabetics because of its beneficial effects on body weight, energy intake, and glucose regulation. However, it has not been investigated how oral metformin affects meal patterns, or whether the reduced food intake is associated with neuronal activation in the hindbrain. Accordingly, we investigated how orally administered metformin (150 or 300 mg/kg daily for 4 or 7 days) reduces body weight in obese mice on a high-fat diet by continuously measuring meal patterns, energy expenditure, and locomotor activity, and whether oral metformin (300 mg/kg daily for 3 days) increases c-Fos expression in the nucleus tractus solitarius (NTS) and area postrema. Furthermore, we determined whether oral metformin produces a conditioned taste aversion (CTA) in obese mice administered a single dose of metformin (75, 150, or 300 mg/kg, p.o.). Metformin (300 mg/kg daily for 7 days) reduced body weight and adiposity by decreasing nocturnal energy intake but did not significantly change energy expenditure or locomotor activity relative to vehicle, and it transiently decreased nocturnal meal size and reduced meal number throughout the experiments. Furthermore, metformin significantly increased c-Fos immunoreactivity within the NTS of obese mice compared to that in controls and pair-fed group, and induced a CTA at doses of 150 or 300 mg/kg. These results indicate that metformin-induced weight loss is associated with a sustained reduction in energy intake maintained by a reduction in meal size and number, and that oral administration of metformin causes visceral illness and neuronal activation in the NTS., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To investigate the distribution of ocular torsion in patients with intermittent exotropia and to determine possible correlation between the torsion and the severity of intermittent exotropia., Design: Prospective, comparative study comprising 600 eyes of 300 children., Methods: One hundred fifty patients with intermittent exotropia between 4 and 15 years of age and another 150 age-matched normal controls without strabismus were enrolled prospectively. Digital nonmydriatic fundus photographs were obtained from both eyes of each subject and the disc-foveal angle was calculated using digital image software. All photographs also were graded as normal, extorsion, or intorsion. We compared the size of the disc-foveal angle between the normal and intermittent exotropia group. We analyzed possible correlations between the disc-foveal angle and disease severity factors, including amount of exotropia, Titmus stereoacuity, and duration of strabismus., Results: Mean disc-foveal angle of intermittent exotropia group was significantly larger than that of normal control group (6.13 and 5.13 degrees, respectively; P < .01). Ocular torsion (either extorsion or intorsion) was discovered in 45 (30%) patients among the intermittent exotropia group, whereas it was found in only 16 (11%) individuals among the normal control group (P < .01). The size of disc-foveal angle showed significant positive correlations with the amount of exotropia and the degree of stereoacuity (r = 0.45, P < .01, and r = 0.51, P < .01, respectively)., Conclusions: Ocular torsion could be found not infrequently in patients with intermittent exotropia. Furthermore, the amount of torsion showed a significant relationship to the disease severity of intermittent exotropia. Assessment of ocular torsion could be used as a supplementary tool for evaluating fusion in patients with intermittent exotropia., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Previously, the authors reported that zaprinast, an inhibitor of cGMP-selective phosphodiesterases, induced the secretions of TNF-α and IL-1β by microglia and enhanced the induction of iNOS by lipopolysaccharide (LPS). In this study, the signaling mechanism responsible for microglial activation by zaprinast was investigated and the effects of zaprinast and LPS on microglial activation were compared. Zaprinast was found to activate ERK1/2, p38 MAPK, JNK, NFκB, and PI3K/Akt, and subsequently, induce the mRNA expressions of IL-1α, IL-1β, TNF-α, CCL2, CCL4, CXCL1, CXCL2, and CD14. Associations between signaling pathways and gene expressions were examined by treating microglia with signal inhibitors. PDTC inhibited the induction of all the above genes by zaprinast, and SB203580 inhibited all genes except CXCL1. SP600125, PD98059, and LY294002 inhibited the induction of at least CCL2. Microglial activation by zaprinast was then compared with full-blown activation by LPS. The zaprinast-induced phosphorylations of MAPKs and IκB were less prompt than LPS-induced phosphorylations. IκB degradation by LPS was significant at 10min and did not return to normal, whereas zaprinast induced a later, transient degradation. LPS induced the mRNA expressions of IL-1β, TNF-α, IL-6, CCL2, iNOS, and COX-2, and although zaprinast significantly induced the expressions of all except IL-6 and iNOS, these inductions were far less than those induced by LPS. Collectively, zaprinast was found to upregulate microglial activity mainly via NFκB and p38 MAPK signaling and the subsequent expressions of inflammatory genes. Although, zaprinast was found to have obvious effects on microglia, these were weaker than the effects of LPS., (Copyright © 2012 Elsevier B.V. All rights reserved.)

To identify and evaluate potentially useful biomarkers for oxidative stress as early warning indices in the polychaete, Perinereis nuntia, we exposed P. nuntia to copper (Cu) and measured several biomarker enzymes (glutathione S-transferase; GST, glutathione peroxidase; GPx, Metallothionein-like protein; MTLPs, and catalase; CAT) and genes (Pn-GSTs, Pn-CAT, and Pn-MT) with a cellular oxidative index, reactive oxygen species (ROS) level. Accumulated Cu concentrations in P. nuntia increased in a time-dependent manner. Intracellular ROS reached high levels 6h after exposure in P. nuntia with an increase of GST activity and glutathione (GSH) content. Particularly, GSH in polychaetes showed a positive correlation with Cu contents accumulated in P. nuntia. Messenger RNA expressions of GST sigma and GST omega showed relatively high expressions at 50 μg/L of Cu exposure, even though the moderate increase of rest of GST isoforms was also observed. Also regarding long-term exposure, we reared P. nuntia in sediments for 15 days, and found that there was an obvious increase of Pn-GSTs, Pn-CAT, and Pn-MT genes with elevated concentrations of Cu and Cd in polychaete body, compared to initial levels, suggesting that P. nuntia in sediment was affected by metals as well as by other organic pollutants to induce oxidative stress genes and enzymes. These findings suggest that oxidative stress is a potential modulator of defense system of P. nuntia. Several potential biomarker genes are available as early warning signals for environmental biomonitoring., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The current study aimed to evaluate immunogenicity and safety of a newly developed diphtheria-tetanus toxoid (Td) vaccine, GC1107 (Green Cross Corporation, Yongin, Korea), in comparison with placebo and active comparator (licensed Td vaccine) in healthy Korean adults. A randomized, double-blind, placebo and active comparator-controlled study was conducted. Forty subjects were randomly administered a single intramuscular dose of GC1107, active comparator or placebo in a ratio of 2:1:1. At 2 and 4 weeks after vaccination, anti-diphtheria antibody levels in the GC1107 group increased 9.2 and 9.3 times, respectively, compared to predose titers. The corresponding values were 9.3 and 8.3 times for the active comparator group. Anti-tetanus antibody levels increased 39.0 and 37.9 fold at 2 and 4 weeks, respectively, after GC1107 administration, and 12.2 and 14.7 fold after active comparator administration. No increases in tetanus or diphtheria antibody were observed for the placebo group. Adverse events in the GC1107 and active comparator groups were more frequent than for the placebo group, but there were no significant differences between the two active treatments. In conclusion, GC1107 was well tolerated and provided significant boosts of anti-tetanus and anti-diphtheria antibodies., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Glutathione S-transferase (GST) is a phase II enzyme that functions as a detoxicant by catalyzing the conjugation of reduced glutathione with a variety of xenobiotics via cysteine thiol. Molecular genetic approaches using gene biomarkers show substantial relevance as sensitive biomarkers for the indication of pollution levels. In order to use GSTs as molecular biomarkers for marine pollution monitoring, we cloned and sequenced the full-length cDNA of seven GST genes from the marine polychaete Perinereis nuntia. The deduced amino acid sequence of Pn-GSTs showed a high similarity to those of other species that clustered into the same clades in a phylogenetic analysis. In addition, to evaluate Pn-GSTs as useful biomarkers on effects after cadmium (Cd) exposure, we exposed sublethal concentrations of Cd (5, 50, and 500 μg/L) to P. nuntia, and they showed relatively different but significantly increases, depending on exposure time and Cd concentrations. Particularly, Pn-GST-omega and Pn-GST-sigma genes were highly sensitive with a clear dose-dependent manner on mRNA expression. The total GST activities also have significantly increased levels at higher concentrations of Cd exposure. These results indicate that Pn-GSTs play important roles in Cd-induced oxidative stress in terms of the physiological changes relating to metabolism and cell protection, and those genes would have great potential as molecular biomarkers to monitor marine environmental health., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Cocaine and amphetamine regulated transcript (CART) has been implicated in the regulation of the stress response. Although the forced swimming test (FST), in which rats are forced to swim for 15 min (pretest swim) and then again for 5 min (test swim) 24 h later, has been used to study the effects of antidepressants, there have been few studies examining the effects of antidepressants on FST-induced changes in CART mRNA levels in the brain. To answer this question, we injected reboxetine and citalopram into male Sprague-Dawley rats 1, 5, and 23.5 h before the test swim and then sacrificed rats 2 h after the test swim, at the peak of the FST-induced increase in CART expression. The FST significantly increased CART mRNA levels in the nucleus accumbens, central nucleus of the amygdala, and locus ceruleus 2 h after the test session. Both reboxetine and citalopram pretreatment blocked FST-induced increases in CART mRNA levels in the nucleus accumbens, central nucleus of the amygdala, and locus ceruleus, despite the fact these antidepressants exert their therapeutic effect by different mechanisms. In addition, the FST significantly increased plasma corticosterone levels, and this effect was also blocked by reboxetine and citalopram pretreatment. These results suggest that inhibition of FST-induced increases in CART expression in the nucleus accumbens, central nucleus of the amygdala, and locus ceruleus may be a common mechanism of antidepressant effects during the FST., (Copyright © 2010 Elsevier B.V. All rights reserved.)

We compared the main characteristics of movement-induced dose reduction during photon and proton beam treatment, based on an analysis of dose-volume histograms. To simulate target movement, a target contour was delineated in a scanned phantom and displaced by 3 to 20 mm. Although the dose reductions to the target in the 2 treatment systems were similar for transverse (perpendicular to beam direction) target motion, they were completely different for longitudinal (parallel to beam direction) target motion. While both modalities showed a relationship between the degree of target shift and the reduction in dose coverage, dose reduction showed a strong directional dependence in proton beam treatment. Clinical simulation of target movement for a prostate cancer patient showed that, although coverage and conformity indices for a 6-mm lateral movement of the prostate were reduced by 9% and 16%, respectively, for proton beam treatment, they were reduced by only 1% and 7%, respectively, for photon treatment. This difference was greater for a 15-mm target movement in the lateral direction, which lowered the coverage and conformity indices by 34% and 54%, respectively, for proton beam treatment, but changed little during photon treatment. In addition, we found that the equivalent uniform dose (EUD) and homogeneity index show similar characteristics during target movement. These results suggest that movement-induced dose reduction differs significantly between photon and proton beam treatment. Attention should be paid to the target margin in proton beam treatment due to the distinct characteristics of heavy ion beams.

MK801 (dizocilpine) induces selective neurotoxic effects in the retrosplenial cortex, ranging from neuronal vacuolization to irreversible neurodegeneration depending on the dose administered. Although lamotrigine prevents MK801-induced neuronal vacuolization in the retrosplenial cortex 4 h after injection, it is not clear whether lamotrigine attenuates the subsequent neurodegeneration that occurs 3-4 days later. Because early growth response factor-1 (egr-1) plays a key role in neurodegeneration and its expression is induced in the retrosplenial cortex following MK801 treatment, it is possible that lamotrigine may attenuate MK801-induced neurodegeneration via inhibition of egr-1 expression in the retrosplenial cortex. To address this issue, we treated rats with lamotrigine (10 or 20 mg/kg) followed by MK801 (2 mg/kg) and measured changes in the levels of egr-1 mRNA and immunoreactivity in the retrosplenial cortex and other brain regions 3 h later. We also evaluated the effects of these treatments on neurodegeneration 4 days following treatment using Fluoro-Jade B staining. MK801 treatment increased egr-1 mRNA and immunoreactivity in the restrosplenial, cingulate, entorhinal and piriform cortices, but decreased levels in hippocampal subfields. These MK801-induced changes in egr-1 expression were significantly inhibited by lamotrigine pretreatment. In addition, MK801-induced neurodegeneration in the retrosplenial cortex was partially blocked by lamotrigine pretreatment in a dose dependent manner. These results demonstrate that lamotrigine pretreatment prevents the MK801-induced upregulation of egr-1 expression in a region-selective manner, and suggest that this effect may contribute, in part, to the attenuation of MK801-induced neurodegeneration in the retrosplenial cortex.

We cloned and sequenced a full-length cDNA of an omega class glutathione S-transferase (GST-O) from the polychaete Neanthes succinea (ns-GST-O). The full-length cDNA of ns-GST-O was 1562 bp in length, containing an open reading frame (OR) of 732 bp that encoded a 244 amino acid protein. The deduced amino acid sequence of ns-GST-O showed a low similarity with the theta class N. suucinea GST (ns-GST-T). As GSTs play a significant role in antioxidant defense, we checked the expression pattern of ns-GST-O in N. succinea after exposure to copper (CuCl(2) 12 to 72 mug/L), which is an oxidative stress-inducing agent. After exposure to CuCl(2), ns-GST-O gene was dramatically up-regulated and when compared with ns-GST-T the expression pattern was more pronounced at all the concentrations of copper. Even the basal transcription levels of ns-GST-O were higher than those of ns-GST-T. To further characterize the catalytic properties of ns-GST-O, we constructed a recombinant ns-GST-O plasmid with a 6x His-Tag at the N-terminal of the full-length ns-GST-O cDNA. Recombinant ns-GST-O protein was highly expressed in transformed Escherichia coli. The effect of pH, temperature and chemical inhibitors on the enzyme activity of ns-GST-O was also studied and compared with the reported effect of these factors on recombinant ns-GST-T protein. These results suggest that, like other types of GSTs, ns-GST-O protein plays a conserved antioxidant role in the polychaete N. succinea.

To investigate whether the anticonvulsant valproate influences the changes in brain-derived neurotrophic factor (BDNF) mRNA expression induced by MK801 in rat brain, we injected valproate prior to MK801 and observed the changes in the BDNF expression 3 h later. MK801 significantly increased BDNF expression in the retrosplenial and entorhinal cortex, and these increases were prevented by valproate pretreatment. Valproate pretreatment significantly blocked the MK801-induced increase of BDNF expression in retrosplenial cortex at 3 h, 6 h, and 9 h after MK801 injection, suggesting that valproate pretreatment did not delay the MK801-induced increase of BDNF expression. However, MK801 significantly decreased BDNF expression in the granule cell layer of hippocampus, and valproate pretreatment before MK801 potentiated the MK801-induced decrease in BDNF expression in granule cell layer. These results indicate that valproate pretreatment differentially affects the MK801-induced changes in BDNF expression in a region-selective manner.

In cultures of the murine macrophage cell line RAW 264.7, effects of four 2'-hydroxychalcone derivatives, 2'-hydroxy-4'-methoxychalcone (compound 1), 2',4-dihydroxy-4'-methoxychalcone (compound 2), 2',4-dihydroxy-6'-methoxychalcone (compound 3) and 2'-hydroxy-4,4'-dimethoxychalcone (compound 4), on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha were examined. Compounds 1, 2 and 3 at 3-30microM inhibited the production with almost the same potency. Compound 4 showed no inhibitory activity. Compounds 1, 2 and 3 at 3-30microM inhibited the LPS-induced expression of inducible nitric oxide synthase (iNOS) and TNF-alpha mRNA. To clarify the mechanism involved, effects of compounds 1, 2 and 3 on the activation of nuclear factor (NF)-kappaB and activator protein-1 (AP-1) were examined. Both the LPS-induced activation of NF-kappaB and AP-1 were blocked by compounds 1, 2 and 3 at 3-30microM. Moreover, the three compounds at such concentrations inhibited the LPS-induced IkappaB degradation and the phosphorylation of c-jun N-terminal kinase (JNK) and c-jun. These findings suggest that the inhibition of the LPS-induced production of NO and TNF-alpha by the 2'-hydroxychalcone derivatives is due to the inhibition of NF-kappaB and AP-1 activations.

Acharan sulfate is a new type of glycosaminoglycan from the giant African snail, Achatina fulica. Acharan sulfate, which has a primary repeating disaccharide structure of alpha-D-N-acetylglucosaminyl-2-O-sulfo-alpha-L-iduronic acid, was studied as a potential antitumor agent in both in vivo and in vitro assays. The antiangiogenic activity of acharan sulfate was evaluated in the chorioallantoic membrane assay and by measuring its effect on the proliferation of calf pulmonary artery endothelial cells. In vivo, a matrigel plug assay showed that acharan sulfate suppressed basic fibroblast growth factor (bFGF)-stimulated angiogenesis and lowered the hemoglobin (Hb) content inside the plug. Acharan sulfate was administered s.c. at two doses for 15 days to C57BL/6 mice implanted with murine Lewis lung carcinoma in the back. It was also administered i.p. to ICR mice bearing sarcoma 180 at a dose of 30 mg/kg. Subcutaneous injection of acharan sulfate at doses of 10 and 30 mg/kg decreased tumor weight and tumor volume by 40% without toxicity or resistance. Intraperitoneal injection of acharan sulfate also decreased tumor weight and volume by 40% in sarcoma 180-bearing mice. These results suggest that the antitumor activity of acharan sulfate may be related to the inhibition of angiogenesis.

Five lignans, l-sesamin, savinin, helioxanthin, taiwanin C, and cis-dibenzylbutyrolactone, were isolated from the root of Acanthopanax chiisanensis (Araliaceae), a Korean medicinal plant, and their inhibitory effects on the production of prostaglandin (PG) E(2) stimulated by 12-O-tetradecanoylphorbol 13-acetate (TPA) in rat peritoneal macrophages were examined. Among the five lignans, taiwanin C was the most potent (IC(50)=0.12 microM), followed by helioxanthin, cis-dibenzylbutyrolactone, and savinin. l-Sesamin had no effect. Taiwanin C showed no inhibitory effect on the TPA-induced release of radioactivity from [3H]arachidonic acid-labeled macrophages, nor did it inhibit the expression of cyclooxygenase (COX)-2 protein induced by TPA. However, the activities of isolated COX-1 and COX-2 were inhibited by taiwanin C (IC(50)=1.06 and 9.31 microM, respectively), reflecting the inhibition of both COX-1- and COX-2-dependent PGE(2) production in the cell culture system. These findings suggest that the mechanism of action of taiwanin C in the inhibition of PGE(2) production is the direct inhibition of COX enzymatic activity.

Multimodality image registration is useful in diagnostic imaging and treatment planning for radiation therapy. In this paper, we present a technique which registers the surfaces of two volumes acquired by different medical imaging modalities. We represent the image volumes in terms of their surface elements known as tiles. We identify the fuzzy variables, assign fuzzy membership functions to them and generate a fuzzy rule database. The fuzzy algorithm reduces the discrepancy between the two set of tiles until the surfaces are matched. In order to study the efficacy of our approach, we severely warp a simulated image and register it with its original. We register CT and MR volumes of humanoid phantom images. Finally, we present the results at the end of the article.

To calculate the dose distribution and the number of monitor unit (MU) per arc, all radiosurgery systems utilize some sort of computer. These computers are, of course, subject to equipment malfunction such as problems with the magnetic tape drive, keyboard, mouse, etc. Since most radiosurgery procedures are quite invasive and time consuming, it is important to have a reliable and reasonably accurate backup system for planning the treatment. This paper will show that a simple PC based system, along with a digitizer, may be used as a backup for a commercial, VAX based radiosurgery system. A complete radiosurgery planning procedure was carried out on a head phantom with a target imbedded inside. The treatment planning and verification using the PC based system is also compared with that using the VAX based system.

The purpose of this study is to evaluate the magnitude of the error in dose delivery caused by the use of open beam depth dose data in dosimetry calculations for wedged photon beams. Isodose plans were calculated for treatments given in a 3-field isocentric prostate or rectal setup using an open AP beam with two lateral wedged beams. The dose distributions were first calculated using open beam depth dose data for all three fields. Next, the open beam data was used only for the AP field and true wedged beam depth dose data was substituted for the two lateral wedged fields. The magnitude of the depth dose variations for wedged vs open beams depends on the nominal beam energy, the wedge angle, and the depth of measurement. Consequently, isodose distributions calculated for wedged fields were found to be different when true wedged beam depth dose data was used instead of open beam data as is commonly done. Monitor unit calculations using a field size specific wedge factor show that dose delivery errors up to 4% can result from the use of open beam depth dose data in wedged beam dose distribution calculations for a 6-MV photon beam. Accurate treatment planning for wedged fields requires the use of wedged beam depth dose data specific to each wedge. Simply using open beam depth dose data in dose calculations for wedged beams will result in dose delivery errors, the magnitude of which depends on the combination of wedge angle, field size, and nominal beam energy.

A simple device for prostate and rectum localization in radiation therapy may be constructed as follows: first, dental wax is used to make up a shape of the rectal probe. Second, dental stone is used to make a two-piece mold by molding the dental wax probe. Third, using the mold, the rectal probe is made from a mixture of silicone and barium. The final step involves the attachment of the "plug," which is made of aluminum. From the simulation films for the prostate setup, the location of the anterior wall of the rectum, anal sphincter, and anal verge can easily be identified, such that the appropriate regions are shielded accordingly. A CT scan with the probe in the rectum did not give too much artifacts from the barium/silicone mixture. The rectal probe with the plug is useful for localizing the prostate more accurately, compared with using the other rectal localization techniques such as barium injection or some rectal markers.

In this study, both a four-field box and two-field AP/PA treatment plan are combined with two insertions of Cs-137 in a tandem and ovoids setup, to evaluate the bioeffects program of a treatment planning system. External beam energies studied are 18 and 6 MV. It is shown that there is a slight difference in the 50-70 time dose fractionation (TDF) isolines when comparing 6 MV and 18 MV, for the AP/PA setup. There is practically no difference for TDF isoline values larger than 80 for both energies with either the four-field or the two-field setup. This is because the brachytherapy contributed the majority of the dose to the regions near the applicator and the TDF values reflect the higher dose delivered by the brachytherapy relative to the external beams in that region. For this simple evaluation of the bioeffects program, the combination of the external beam plan and the brachytherapy plan does not give us enhanced information on the effectiveness of the plan.

The Atomlab 44D well-type ionization chamber is being evaluated for calibration of high dose rate (HDR) Ir-192 and low dose rate (LDR) Cs-137 sources. The chamber has a flat response (sweet spot) of +/- 0.5% along approximately 3.5 cm for an Ir-192 HDR linear source and 3 cm for a Cs-137 LDR spherical source. The short-term stability of the chamber was determined using a cylindrical Cs-137 source positioned in the sweet spot region. The chamber response over a range of 17.4 mCi (644 MBq, Cs-137) and 8.82 Ci (326 GBq, Ir-192) is evaluated. The chamber may be used for calibrating the activities of both HDR Ir-192 and LDR brachytherapy sources.

Two methods are shown here to determine the 50% depth ionization (d50) using buildup materials of different thickness placed on top of a five-chamber detector array. In the first method, two sets of different thickness buildup material are required to perform the check, one set for checking 6 and 9 MeV, while another set is used for 12, 16, and 20 MeV electron beam from a Varian Clinac 2100C. The second method only requires two data points to determine the d50 depth for each energy. The d50 depths determined were compared with the d50 depth obtained using a water phantom with ionization chamber measurements. The method is simple to use especially for departments that use a similar detector to perform quality assurance tests such as output/symmetry/flatness check.

The state of p53 tumour suppressor and the frequency of high-risk human papillomavirus (HPV) infections were studied in nine human oral cancer cell lines. Three cancer cell lines (SCC-4, Tu-177 and FaDu) had similar amounts of p53 transcripts to normal cells, but contained significantly higher levels of p53 protein than the normal control cells. Sequencing highly conserved open reading frames of the p53 gene of these cancer cells showed point mutations in the SCC-4 and Tu-177 cell lines, a base transition from CCC to TCC occurred at codon 151; and in the line FaDu, a mutation of CGG to CTG occurred at codon 248. The HEp-2 and 1483 cancer lines contained significantly lower levels of p53 protein compared to the normal counterpart. Sequencing of p53 cDNA for HEp-2 and 1483 lines showed no mutations, but northern analysis revealed that these cell lines expressed HPV-18 E6/E7 messages. Four cell lines (SCC-9, SCC-15, SCC-25, and Tu-139) expressed negligible amounts of p53 transcripts compared to the normal counterpart and undetectable levels of p53 protein. These cell lines contained mutations in the highly conserved open reading frames of the p53 gene as follows: the SCC-9 had a deletion of 32 base pairs between codons 274 and 285; the line SCC-15 had an insertion of five base pairs between codons 224 and 225; the line SCC-25 had a deletion of two base pairs in codon 209; and the Tu-139 line had a deletion of 46 base pairs between codons 171 and 186.(ABSTRACT TRUNCATED AT 250 WORDS)

The Nucletron Plato system is being used in our Institute for both high dose rate (HDR) and low dose rate (LDR) treatment planning, while the radiation oncology computer system (ROCS) is used for external beam planning. This paper compares both systems, using a gynecological application for the LDR case and an esophageal application for the HDR. It is shown that ROCS may be used as a backup to the Nucletron treatment planning system for LDR and simple HDR cases. The Nucletron planning system is a better system than ROCS for both LDR and HDR applications.