[Protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats].

PubMed

Mu, F H; Hu, F L; Wei, H; Zhang, Y Y; Yang, G B; Lei, X Y; Yang, Y P; Sun, W N; Cui, M H

2016-02-01

To investigate the protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats and its possible mechanism. Acute gastric mucosal injury model was developed with intraperitoneal injection of aspirin in Wistar rats. The rats were divided into normal control group, injury group, sucralfate protection group, compound bismuth and magnesium granules protection group and its herbal components protection group(each group 12 rats). In the protection groups, drugs as mentioned above were administered by gavage before treated with intraperitoneal injection of aspirin. To evaluate the extent of gastric mucosal injury and the protective effect of drugs, gastric mucosal lesion index, gastric mucosal blood flow, content of gastric mucosal hexosamine, prostaglandins (PG), nitric oxide(NO), tumor necrosis factor (TNF), and interleukin (IL) -1, 2, 8 were measured in each group, and histological changes were observed by gross as well as under microscope and electron microscope. Contents of hexosamine, NO, and PG in all the protection groups were significantly higher than those in the injury group (all P<0.01), and content of NO in the compound bismuth and magnesium granules group was significantly higher than that in the sucralfate group ((11.29±0.51) vs(10.80±0.36)nmol/ml, P<0.05). The gastric mucosal lesion index, contents of TNF, and IL-1, 2, 8 were significantly lower in all the protection groups than in the injury group (all P<0.01), and contents of IL-2 and IL-8 in the compound bismuth and magnesium granules group were significantly lower than those in the sucralfate group ((328.17±6.56) vs(340.23±8.05)pg/ml, P<0.01; (170.82±7.31) vs(179.31±7.80)pg/ml, P<0.05). Tissue injury and inflammatory reaction in all the protection groups were obviously mitigated compared with the injury group. Compound bismuth and magnesium granules and its herbal components may have significant protective effect on aspirin-induced gastric mucosal injury.

DIFFERENTIATING TOXICITIES OF CONAZOLE FUNGICIDES THROUGH METABONOMIC ANALYSES OF MULTIPLE TISSUES

EPA Science Inventory

The conazole fungicides represent a large group of compounds widely used agriculturally for the protection of crop plants (Hutson 1998) and pharmaceutically in the treatment of topical and systemic infections (Sheehan 1999). In 1999, the latest period for which agricultural usage...

DIFFERENTIATING TOXICITIES OF CONAZOLE FUNGICIDES THROUGH METABONOMIC ANALYSES OF MULTIPLE TISSUES

EPA Science Inventory

The conazole fungicides represent a large group of compounds widely used agriculturally for the protection of crop plants (Hutson 1998) and pharmaceutically in the treatment of topical and systemic infections(Sheehan 1999). In 1999, the latest period for which agricultural usage...

Arginine-specific gingipains from Porphyromonas gingivalis deprive protective functions of secretory leucocyte protease inhibitor in periodontal tissue

PubMed Central

Into, T; Inomata, M; Kanno, Y; Matsuyama, T; Machigashira, M; Izumi, Y; Imamura, T; Nakashima, M; Noguchi, T; Matsushita, K

2006-01-01

Chronic periodontitis is correlated with Porphyromonas gingivalis infection. In this study, we found that the expression of secretory leucocyte protease inhibitor (SLPI), an endogenous inhibitor for neutrophil-derived proteases, was reduced in gingival tissues with chronic periodontitis associated with P. gingivalis infection. The addition of vesicles of P. gingivalis decreased the amount of SLPI in the media of primary human gingival keratinocytes compared to untreated cultures. We therefore investigated how arginine-specific gingipains (Rgps) affect the functions of SLPI, because Rgps are the major virulence factors in the vesicles and cleave a wide range of in-host proteins. We found that Rgps digest SLPI in vitro, suppressing the release of SLPI. Rgps proteolysis of SLPI disrupted SLPI functions, which normally suppresses neutrophil elastase and neutralizes pro-inflammatory effects of bacterial cell wall compounds in cultured human gingival fibroblasts. The protease inhibitory action of SLPI was not exerted towards Rgps. These results suggest that Rgps reduce the protective effects of SLPI on neutrophil proteases and bacterial proinflammatory compounds, by which disease in gingival tissue may be accelerated at the sites with P. gingivalis infection. PMID:16907925

Organochlorine compounds and trace elements in fish tissue and bed sediments in the lower Snake River basin, Idaho and Oregon

USGS Publications Warehouse

Clark, Gregory M.; Maret, Terry R.

1998-01-01

Fish-tissue and bed-sediment samples were collected to determine the occurrence and distribution of organochlorine compounds and trace elements in the lower Snake River Basin. Whole-body composite samples of suckers and carp from seven sites were analyzed for organochlorine compounds; liver samples were analyzed for trace elements. Fillets from selected sportfish were analyzed for organochlorine compounds and trace elements. Bed-sediment samples from three sites were analyzed for organochlorine compounds and trace elements. Twelve different organochlorine compounds were detected in 14 fish-tissue samples. All fish-tissue samples contained DDT or its metabolites. Concentrations of total DDT ranged from 11 micrograms per kilogram wet weight in fillets of yellow perch from C.J. Strike Reservoir to 3,633 micrograms per kilogram wet weight in a whole-body sample of carp from Brownlee Reservoir at Burnt River. Total DDT concentrations in whole-body samples of sucker and carp from the Snake River at C.J. Strike Reservoir, Snake River at Swan Falls, Snake River at Nyssa, and Brownlee Reservoir at Burnt River exceeded criteria established for the protection of fish-eating wildlife. Total PCB concentrations in a whole-body sample of carp from Brownlee Reservoir at Burnt River also exceeded fish-eating wildlife criteria. Concentrations of organochlorine compounds in whole-body samples, in general, were larger than concentrations in sportfish fillets. However, concentrations of dieldrin and total DDT in fillets of channel catfish from the Snake River at Nyssa and Brownlee Reservoir at Burnt River, and concentrations of total DDT in fillets of smallmouth bass and white crappie from Brownlee Reservoir at Burnt River exceeded a cancer risk screening value of 10-6 established by the U.S. Environmental Protection Agency. Concentrations of organochlorine compounds in bed sediment were smaller than concentrations in fish tissue. Concentrations of p,p'DDE, the only compound detected in all three bed-sediment samples, ranged from 1.1 micrograms per kilogram dry weight in C.J. Strike Reservoir to 11 micrograms per kilogram dry weight in Brownlee Reservoir at Burnt River. Data from this study, compared with data collected in the upper Snake River Basin from 1992 to 1994, indicates that, in general, organochlorine concentrations in fish tissue and bed sediment increased from the headwaters of the Snake River in Wyoming downstream to Brownlee Reservoir. The largest trace-element concentrations in fish tissue were in liver samples from carp from Brownlee Reservoir at Burnt River and suckers from the Boise River near Twin Springs. Concentrations of most trace elements were larger in livers than in the sport- fish fillets. However, mercury concentrations were generally larger in the sportfish fillets; they ranged from 0.08 microgram per gram wet weight in yellow perch from C.J. Strike Reservoir to 0.32 microgram per gram wet weight in channel catfish from Brownlee Reservoir at Burnt River. None of the trace-element concentrations in fillets exceeded median international standards or U.S. Food and Drug Administration action levels. Large trace-element concentrations in the upper Snake River Basin were reported in liver samples from suckers from headwater streams, probably a result of historical mining and weathering of metal-rich rocks. Concentrations of most trace elements in the bed-sediment samples were largest in Brownlee Reservoir at Mountain Man Lodge. Concentrations of arsenic, cadmium, chromium, copper, nickel, and zinc in bed sediment from the Mountain Man Lodge site exceeded either the threshold effect level or probable effect level established by the Canadian Government for the protection of benthic life. Arsenic, chromium, copper, and nickel concentrations in bed sediment from Brownlee Reservoir at Burnt River and chromium, copper, and nickel in bed sediment from C.J. Strike Reservoir also exceeded the threshold effect level.

Antioxidant enrichment and antimicrobial protection of fresh-cut fruits using their own byproducts: looking for integral exploitation.

PubMed

Ayala-Zavala, J F; Rosas-Domínguez, C; Vega-Vega, V; González-Aguilar, G A

2010-10-01

Fresh-cut fruit consumption is increasing due to the rising public demand for convenience and awareness of fresh-cut fruit's health benefits. The entire tissue of fruits and vegetables is rich in bioactive compounds, such as phenolic compounds, carotenoids, and vitamins. The fresh-cut fruit industry deals with the perishable character of its products and the large percentage of byproducts, such as peels, seeds, and unused flesh that are generated by different steps of the industrial process. In most cases, the wasted byproducts can present similar or even higher contents of antioxidant and antimicrobial compounds than the final produce can. In this context, this hypothesis article finds that the antioxidant enrichment and antimicrobial protection of fresh-cut fruits, provided by the fruit's own byproducts, could be possible.

Antioxidant Enrichment and Antimicrobial Protection of Fresh-Cut Fruits Using Their Own Byproducts: Looking for Integral Exploitation

PubMed Central

Ayala-Zavala, JF; Rosas-Domínguez, C; Vega-Vega, V; González-Aguilar, GA

2010-01-01

Fresh-cut fruit consumption is increasing due to the rising public demand for convenience and awareness of fresh-cut fruit's health benefits. The entire tissue of fruits and vegetables is rich in bioactive compounds, such as phenolic compounds, carotenoids, and vitamins. The fresh-cut fruit industry deals with the perishable character of its products and the large percentage of byproducts, such as peels, seeds, and unused flesh that are generated by different steps of the industrial process. In most cases, the wasted byproducts can present similar or even higher contents of antioxidant and antimicrobial compounds than the final produce can. In this context, this hypothesis article finds that the antioxidant enrichment and antimicrobial protection of fresh-cut fruits, provided by the fruit's own byproducts, could be possible. PMID:21535513

Protection of macaques from vaginal SHIV challenge by vaginally delivered inhibitors of virus-cell fusion.

PubMed

Veazey, Ronald S; Klasse, Per Johan; Schader, Susan M; Hu, Qinxue; Ketas, Thomas J; Lu, Min; Marx, Preston A; Dufour, Jason; Colonno, Richard J; Shattock, Robin J; Springer, Martin S; Moore, John P

2005-11-03

Human immunodeficiency virus type 1 (HIV-1) continues to spread, principally by heterosexual sex, but no vaccine is available. Hence, alternative prevention methods are needed to supplement educational and behavioural-modification programmes. One such approach is a vaginal microbicide: the application of inhibitory compounds before intercourse. Here, we have evaluated the microbicide concept using the rhesus macaque 'high dose' vaginal transmission model with a CCR5-receptor-using simian-human immunodeficiency virus (SHIV-162P3) and three compounds that inhibit different stages of the virus-cell attachment and entry process. These compounds are BMS-378806, a small molecule that binds the viral gp120 glycoprotein and prevents its attachment to the CD4 and CCR5 receptors, CMPD167, a small molecule that binds to CCR5 to inhibit gp120 association, and C52L, a bacterially expressed peptide inhibitor of gp41-mediated fusion. In vitro, all three compounds inhibit infection of T cells and cervical tissue explants, and C52L acts synergistically with CMPD167 or BMS-378806 to inhibit infection of cell lines. In vivo, significant protection was achieved using each compound alone and in combinations. CMPD167 and BMS-378806 were protective even when applied 6 h before challenge.

[The biological and clinical relevance of estrogen metabolome].

PubMed

Kovács, Krisztián; Vásárhelyi, Barna; Mészáros, Katalin; Patócs, Attila; Karvaly, Gellért

2017-06-01

Considerable knowledge has been gathered on the physiological role of estrogens. However, fairly little information is available on the role of compounds produced in the breakdown process of estrone and estradiol wich may play a role in various diseases associated with estrogen impact. To date, approximately 15 extragonadal estrogen-related compounds have been identified. These metabolites may exert protective, or, instead, pro-inflammatory and/or pro-oncogenic activity in a tissue-specific manner. Systemic and local estrogen metabolite levels are not necesserily correlated, which may promote the diagnostic significance of the locally produced estrogen metabolites in the future. The aim of the present study is a bibliographic review of the extragonadal metabolome in peripheral tissues, and to highlight the role of the peripheral tissue homeostasis of estrogens as well as the non-hormonal biological activity and clinical significance of the estrogen metabolome. Orv Hetil. 2017; 158(24): 929-937.

Novel Apigenin Based Small Molecule that Targets Snake Venom Metalloproteases

PubMed Central

Anusha, Sebastian; Hemshekhar, Mahadevappa; Chandra Nayaka, Siddaiah; Kemparaju, Kempaiah; Basappa; Girish, Kesturu S.; Rangappa, Kanchugarakoppal S.

2014-01-01

The classical antivenom therapy has appreciably reduced snakebite mortality rate and thus is the only savior drug available. Unfortunately, it considerably fails to shield the viper bite complications like hemorrhage, local tissue degradation and necrosis responsible for severe morbidity. Moreover, the therapy is also tagged with limitations including anaphylaxis, serum sickness and poor availability. Over the last decade, snake venom metalloproteases (SVMPs) are reported to be the primary component responsible for hemorrhage and tissue degradation at bitten site. Thus, antivenom inability to offset viper venom-induced local toxicity has been a basis for an insistent search for SVMP inhibitors. Here we report the inhibitory effect of compound 5d, an apigenin based molecule against SVMPs both in silico and in vivo. Several apigenin analogues are synthesized using multicomponent Ugi reactions. Among them, compound 5d effectively abrogated Echis carinatus (EC) venom-induced local hemorrhage, tissue necrosis and myotoxicity in a dose dependant fashion. The histopathological study further conferred effective inhibition of basement membrane degradation, and accumulation of inflammatory leucocytes at the site of EC venom inoculation. The compound also protected EC venom-induced fibrin and fibrinogen degradation. The molecular docking of compound 5d and bothropasin demonstrated the direct interaction of hydroxyl group of compound with Glu146 present in hydrophobic pocket of active site and does not chelate Zn2+. Hence, it is concluded that compound 5d could be a potent agent in viper bite management. PMID:25184206

Rebamipide induces the gastric mucosal protective factor, cyclooxygenase-2, via activation of 5'-AMP-activated protein kinase.

PubMed

Lee, Sunyoung; Jeong, Seongkeun; Kim, Wooseong; Kim, Dohoon; Yang, Yejin; Yoon, Jeong-Hyun; Kim, Byung Joo; Min, Do Sik; Jung, Yunjin

2017-01-29

Rebamipide, an amino acid derivative of 2(1H)-quinolinone, has been used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. Induction of cyclooxygenase (COX)-2, a gastric mucosal protective factor, by rebamipide has been suggested as the major mechanism of the drug action. However, how rebamipide induces COX-2 at the molecular level needs further investigation. In this study, the molecular mechanism underlying the induction of COX-2 by rebamipide was investigated. In gastric carcinoma cells and macrophage cells, rebamipide induced phosphorylation of AMP-activated protein kinase (AMPK), leading to phosphorylation of acetyl-CoA carboxylase (ACC), a substrate of AMPK. The induction of COX-2 by rebamipide was dependent on AMPK activation because compound C, an AMPK inhibitor, abolished COX-2 induction by rebamipide. In a mouse ulcer model, rebamipide protected against hydrochloric acid/ethanol-induced gastric ulcer, and these protective effects were deterred by co-administration of compound C. In parallel, in the gastric tissues, rebamipide increased the phosphorylation AMPK, whereas compound C reduced the levels of COX-2 and phosphorylated ACC, which were increased by rebamipide. Taken together, the activation of AMPK by rebamipide may be a molecular mechanism that contributes to induction of COX-2, probably resulting in protection against gastric ulcers. Copyright © 2016 Elsevier Inc. All rights reserved.

Concentrations of chlorinated organic compounds in biota and bed sediment in streams of the San Joaquin Valley, California

USGS Publications Warehouse

Brown, L.R.

1997-01-01

Samples of resident biota and bed sediments were collected in 1992 from 18 sites on or near the floor of the San Joaquin Valley, California, for analysis of 33 organochlorine compounds. The sites were divided into five groups on the basis of physiographic region and land use. Ten compounds were detected in tissue, and 15 compounds were detected in bed sediment. The most frequently detected compound in both media was p,p'-DDE. Concentrations of ??DDT (sum of o,p'- and p, p' forms of DDD, DDE, and DDT) were statistically different among groups of sites for both tissue and sediment (Kruskal- Wallis, p < 0.05). Concentrations in both media were highest in streams draining the west side of the valley. Concentrations of ??DDT in tissue were significantly correlated with specific conductance, pH, and total alkalinity (p < 0.05), which are indicators of the proportion of irrigation return flows in stream discharge. Concentrations in sediment on a dry-weight basis were not correlated with these water-quality parameters, but total organic carbon (TOC) normalized concentrations were significantly correlated with specific conductance and pH (p < 0.05). Regressions of the concentration of ??DDT in tissue, as a function of ??DDT in bed sediment, were significant and explained up to 76% of the variance in the data. The concentration of ??DDT in sediment may be related to mechanisms of soil transport to surface water with bioavailability of compounds related to the concentration of TOC in sediment. The results of this study did not indicate any clear advantage to using either bed sediment or tissues in studies of organochlorine chemicals in the environment. Some guidelines for protection of fish and wildlife were exceeded. Concentrations of organochlorine chemicals in biota, and perhaps sediment, have declined from concentrations measured in the 1970s and 1980s, but remain high compared to other regions of the United States.

Involvement of the Electrophilic Isothiocyanate Sulforaphane in Arabidopsis Local Defense Responses1

PubMed Central

Andersson, Mats X.; Nilsson, Anders K.; Johansson, Oskar N.; Boztaş, Gülin; Adolfsson, Lisa E.; Pinosa, Francesco; Petit, Christel Garcia; Aronsson, Henrik; Mackey, David; Tör, Mahmut; Hamberg, Mats; Ellerström, Mats

2015-01-01

Plants defend themselves against microbial pathogens through a range of highly sophisticated and integrated molecular systems. Recognition of pathogen-secreted effector proteins often triggers the hypersensitive response (HR), a complex multicellular defense reaction where programmed cell death of cells surrounding the primary site of infection is a prominent feature. Even though the HR was described almost a century ago, cell-to-cell factors acting at the local level generating the full defense reaction have remained obscure. In this study, we sought to identify diffusible molecules produced during the HR that could induce cell death in naive tissue. We found that 4-methylsulfinylbutyl isothiocyanate (sulforaphane) is released by Arabidopsis (Arabidopsis thaliana) leaf tissue undergoing the HR and that this compound induces cell death as well as primes defense in naive tissue. Two different mutants impaired in the pathogen-induced accumulation of sulforaphane displayed attenuated programmed cell death upon bacterial and oomycete effector recognition as well as decreased resistance to several isolates of the plant pathogen Hyaloperonospora arabidopsidis. Treatment with sulforaphane provided protection against a virulent H. arabidopsidis isolate. Glucosinolate breakdown products are recognized as antifeeding compounds toward insects and recently also as intracellular signaling and bacteriostatic molecules in Arabidopsis. The data presented here indicate that these compounds also trigger local defense responses in Arabidopsis tissue. PMID:25371552

Nanoparticles and Controlled Delivery for Bioactive Compounds: Outlining Challenges for New “Smart-Foods” for Health

PubMed Central

Martínez-Ballesta, MCarment; García-Viguera, Cristina

2018-01-01

Nanotechnology is a field of research that has been stressed as a very valuable approach for the prevention and treatment of different human health disorders. This has been stressed as a delivery system for the therapeutic fight against an array of pathophysiological situations. Actually, industry has applied this technology in the search for new oral delivery alternatives obtained upon the modification of the solubility properties of bioactive compounds. Significant works have been made in the last years for testing the input that nanomaterials and nanoparticles provide for an array of pathophysiological situations. In this frame, this review addresses general questions concerning the extent to which nanoparticles offer alternatives that improve therapeutic value, while avoid toxicity, by releasing bioactive compounds specifically to target tissues affected by specific chemical and pathophysiological settings. In this regard, to date, the contribution of nanoparticles to protect encapsulated bioactive compounds from degradation as a result of gastrointestinal digestion and cellular metabolism, to enable their release in a controlled manner, enhancing biodistribution of bioactive compounds, and to allow them to target those tissues affected by biological disturbances has been demonstrated. PMID:29735897

Protective Effect of Pyruvate Against Radiation-Induced Damage in Collagenized Tissues

NASA Technical Reports Server (NTRS)

Griko, Y. V.; Yan, Xiaoli

2016-01-01

Exposure to high doses of ionizing radiation produces both acute and late effects on the collagenized tissues and have profound effects on wound healing. Because of the crucial practical importance for new radioprotective agents, our study has been focused on evaluation of the efficacy of non-toxic naturally occurring compounds to protect tissue integrity against high-dose gamma radiation. Here, we demonstrate that molecular integrity of collagen may serve as a sensitive biological marker for quantitative evaluation of molecular damage to collagenized tissue and efficacy of radioprotective agents. Increasing doses of gamma radiation (0-50kGy) result in progressive destruction of the native collagen fibrils, which provide a structural framework, strength, and proper milieu for the regenerating tissue. The strategy used in this study involved the thermodynamic specification of all structural changes in collagenized matrix of skin, aortic heart valve, and bone tissue induced by different doses and conditions of g-irradiation. This study describes a simple biophysical approach utilizing the Differential Scanning Calorimetry (DSC) to characterize the structural resistance of the aortic valve matrix exposed to different doses of g-irradiation. It allows us to identify the specific response of each constituent as well as to determine the influence of the different treatments on the characteristic parameters of protein structure. We found that pyruvate, a substance that naturally occurs in the body, provide significant protection (up to 80%) from biochemical and biomechanical damage to the collagenized tissue through the effective targeting of reactive oxygen species. The recently discovered role of pyruvate in the cell antioxidant defense to O2 oxidation, and its essential constituency in the daily human diet, indicate that the administration of pyruvate-based radioprotective formulations may provide safe and effective protection from deleterious effects of ionizing radiation.

Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against Light-Induced Oxidative Damage in Rat Retina

PubMed Central

Ishihara, Tomoe; Kaidzu, Sachiko; Kimura, Hideto; Koyama, Yasurou; Matsuoka, Yotaro

2018-01-01

Retinal tissue is exposed to oxidative stress caused by visible light. Light-damaged rat used in age-related macular degeneration (AMD) studies clarified that antioxidants decrease retinal light damage. Albino rats were exposed to 5000 Lux light for 12 h with oral administration of the polyphenolic compounds fraction (PF) from the seed shells of Japanese horse chestnut (30 mg/kg, 100 mg/kg, and 300 mg/kg body weight: BW). To evaluate the protective effects against light damage, electroretinograms (ERGs), the outer nuclear layer (ONL) thickness, the antioxidant activity of plasma, oxidized retinal lipids, and the detection of apoptosis were examined. To reveal their active compounds, PF were separated into an A-type proanthocyanidin (PAF) and a flavonol O-glycosides fraction. The protective effects of these fractions against light damage were compared by measuring the thickness of the ERGs and ONL. Compared with the negative control, the PF group (100 mg/kg and 300 mg/kg BW) significantly suppressed the decrease of the ERG amplitudes and ONL thickness. PF (300 mg/kg BW) induced the elevation of in vivo antioxidant activity, and the suppression of retinal lipid oxidation. PF administration also suppressed apoptotic cell death. The protective effects against light damage were attributable to the antioxidant activity of PAF. The light-induced damage of retinas was protected by oral administration of PF and PAF. Taken together, these compounds are potentially useful for the prevention of the disease caused by light exposure. Highlights: The protective effects of retinal damage by light exposure were evaluated using polyphenolic compounds from the seed shells of Japanese horse chestnut (Aesculus turbinata BLUME) as an antioxidant. Decreases in the electroretinographic amplitude and outer nuclear layer thickness were suppressed by the polyphenolic compounds of the seed shells. Polyphenolic compounds from the seed shells of Japanese horse chestnut inhibited the oxidation of retinal lipids. Highly polymeric A-type proanthocyanidin from the seed shells protected the rat retina from light exposure damage by inhibiting oxidative stress and apoptotic mechanisms. PMID:29748512

Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against Light-Induced Oxidative Damage in Rat Retina.

PubMed

Ishihara, Tomoe; Kaidzu, Sachiko; Kimura, Hideto; Koyama, Yasurou; Matsuoka, Yotaro; Ohira, Akihiro

2018-05-10

Retinal tissue is exposed to oxidative stress caused by visible light. Light-damaged rat used in age-related macular degeneration (AMD) studies clarified that antioxidants decrease retinal light damage. Albino rats were exposed to 5000 Lux light for 12 h with oral administration of the polyphenolic compounds fraction (PF) from the seed shells of Japanese horse chestnut (30 mg/kg, 100 mg/kg, and 300 mg/kg body weight: BW). To evaluate the protective effects against light damage, electroretinograms (ERGs), the outer nuclear layer (ONL) thickness, the antioxidant activity of plasma, oxidized retinal lipids, and the detection of apoptosis were examined. To reveal their active compounds, PF were separated into an A-type proanthocyanidin (PAF) and a flavonol O -glycosides fraction. The protective effects of these fractions against light damage were compared by measuring the thickness of the ERGs and ONL. Compared with the negative control, the PF group (100 mg/kg and 300 mg/kg BW) significantly suppressed the decrease of the ERG amplitudes and ONL thickness. PF (300 mg/kg BW) induced the elevation of in vivo antioxidant activity, and the suppression of retinal lipid oxidation. PF administration also suppressed apoptotic cell death. The protective effects against light damage were attributable to the antioxidant activity of PAF. The light-induced damage of retinas was protected by oral administration of PF and PAF. Taken together, these compounds are potentially useful for the prevention of the disease caused by light exposure. The protective effects of retinal damage by light exposure were evaluated using polyphenolic compounds from the seed shells of Japanese horse chestnut ( Aesculus turbinata BLUME) as an antioxidant. Decreases in the electroretinographic amplitude and outer nuclear layer thickness were suppressed by the polyphenolic compounds of the seed shells. Polyphenolic compounds from the seed shells of Japanese horse chestnut inhibited the oxidation of retinal lipids. Highly polymeric A-type proanthocyanidin from the seed shells protected the rat retina from light exposure damage by inhibiting oxidative stress and apoptotic mechanisms.

Anti-Inflammatory and Anti-Obesity Properties of Food Bioactive Components: Effects on Adipose Tissue

PubMed Central

Jayarathne, Shasika; Koboziev, Iurii; Park, Oak-Hee; Oldewage-Theron, Wilna; Shen, Chwan-Li; Moustaid-Moussa, Naima

2017-01-01

Obesity is an epidemic and costly disease affecting 13% of the adult population worldwide. Obesity is associated with adipose tissue hypertrophy and hyperplasia, as well as pathologic endocrine alterations of adipose tissue including local and chronic systemic low-grade inflammation. Moreover, this inflammation is a risk factor for both metabolic syndrome (MetS) and insulin resistance. Basic and clinical studies demonstrate that foods containing bioactive compounds are capable of preventing both obesity and adipose tissue inflammation, improving obesity-associated MetS in human subjects and animal models of obesity. In this review, we discuss the anti-obesity and anti-inflammatory protective effects of some bioactive polyphenols of plant origin and omega-3 polyunsaturated fatty acids, available for the customers worldwide from commonly used foods and/or as components of commercial food supplements. We review how these bioactive compounds modulate cell signaling including through the nuclear factor-κB, adenosine monophosphate-activated protein kinase, mitogen-activated protein kinase, toll-like receptors, and G-protein coupled receptor 120 intracellular signaling pathways and improve the balance of pro- and anti-inflammatory mediators secreted by adipose tissue and subsequently lower systemic inflammation and risk for metabolic diseases. PMID:29333376

Comparative behavioral toxicity of four sulfhydryl radioprotective compounds in mice: Wr2721, cysteamine, diethyldithiocarbamate, and n-acetylcysteine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Landauer, M.R.; Davis, H.D.; Dominitz, J.A.

1988-01-01

A number of sulfhydryl compounds have been shown to protect against ionizing radiation. One of the most effective radioprotectors is S-2(3-aminopropylamino)ethylphosphorothioic acid, also known aas ethiofos, gammaphos, or WR-2721 (Davidson, 1980; Giambarresi and Jacobs, 1987). This drug is currently under clinical investigation for its potential in protecting normal tissue during radiation treatment and chemotherapy (Blumberg et al., 1982; Glover et al., 1988; Yuhas et al., 1980). B-Mercaptoethylamine (MEA, cysteamine) was for years the standard against which the effectiveness of other radioprotectors was judged, but is more toxic than WR-2721 (Giambarresi and Jacobs, 1987). Diethyldithiocarbamate (DDC) and N-acetylcysteine (NAC) are othermore » compounds shown to have radioprotective properties (Milas et al., 1988; Weiss et al., 1984). Studies in a variety of animal species have shown significant behavioral toxicity after administration of WR-2721 (Bogo et al., 1985; Bogo, 1988; Landauer et al., 1987b, 1988).« less

Occurrence and distribution of organochlorine pesticides, polychlorinated biphenyls, and trace elements in fish tissue in the lower Tennessee River basin, 1980-98

USGS Publications Warehouse

Knight, R.R.; Powell, J.R.

2001-01-01

The U.S. Geological Survey, as part of the National Water-Quality Assessment Program, evaluated the occurrence and distribution of organochlorine pesticides, polychlorinated biphenyls, and trace elements in fish tissue in samples collected in the lower Tennessee River Basin study unit. Fish tissue analysis provides a time-averaged measurement of contaminants as well as a direct measurement of the contaminants that bioaccumulate in fish tissue. Bioaccumulation of contaminants in fish tissue may result in concentrations that can affect human, wildlife, or aquatic health. Data for two types of tissue analyses were evaluated to assess the occurrence and distribution of contaminants: whole fish for organochlorine pesticides and polychlorinated biphenyls and fish fillets for organochlorine pesticides, polychlorinated biphenyls, and trace elements. The fish tissue data analyzed for this study cover an 18-year span including data collected in 1998 by the U.S. Geological Survey as part of the National Water-Quality Assessment Program; data collected from 1980 through 1997 by the Tennessee Valley Authority; and data collected from 1992 through 1997 by the Tennessee Department of Environment and Conservation. Concentration data for constituents that are on the U.S. Environmental Protection Agency Priority Pollutant List were summarized and compared against existing action levels or guidelines.From the list of organochlorine pesticide compounds analyzed, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), a breakdown product of dichlorodiphenyltrichloroethane (DDT), was the most commonly detected compound with detections at 83 percent of the sites sampled. Eleven p,p'-DDE samples exceeded action levels or guidelines with concentrations ranging from 0.20 to 12.8 milligrams per kilogram. Five other organochlorine compounds, p,p'-dichlorodiphenyldichloroethane (p,p'-DDD), dieldrin, endrin, chlordane, and polychlorinated biphenyls, also exceeded action levels and guidelines, but the detection frequencies at sampling sites generally were less than 70 percent. Mercury, the only trace element to exceed a guideline, was detected at 51 of 102 sites sampled for trace elements. Selenium was detected in fish fillet samples from 70 of 102 sites sampled, which was more sites than for any other trace element; however, selenium did not exceed the 50 micrograms per gram U.S. Environmental Protection Agency screening criteria. Arsenic and cadmium also were detected at 44 and 54 percent of the sampling sites, respectively.

Intra-plant variation in cyanogenesis and the continuum of foliar plant defense traits in the rainforest tree Ryparosa kurrangii (Achariaceae).

PubMed

Webber, Bruce L; Woodrow, Ian E

2008-06-01

At the intra-plant level, temporal and spatial variations in plant defense traits can be influenced by resource requirements, defensive priorities and storage opportunities. Across a leaf age gradient, cyanogenic glycoside concentrations in the rainforest understory tree Ryparosa kurrangii B.L. Webber were higher in young expanding leaves than in mature leaves (2.58 and 1.38 mg g(-1), respectively). Moreover, cyanogens, as an effective chemical defense against generalist herbivores, contributed to a defense continuum protecting foliar tissue during leaf development. Chemical (cyanogens and phenolic compounds) and phenological (delayed greening) defense traits protected young leaves, whereas mature leaves were largely protected by physical defense mechanisms (lamina toughness; explained primarily by leaf mass per area). Cyanogen concentration was considerably higher in floral tissue than in foliar tissue and decreased in floral tissue during development. Across contrasting tropical seasons, foliar cyanogenic concentration varied significantly, being highest in the late wet season and lowest during the pre-wet season, the latter coinciding with fruiting and leaf flushing. Cyanogens in R. kurrangii appear to be differentially allocated in a way that maximizes plant fitness but may also act as a store of reduced nitrogen that is remobilized during flowering and leaf flushing.

Translocation of the neonicotinoid seed treatment clothianidin in maize

PubMed Central

Krupke, Christian H.

2017-01-01

Neonicotinoid seed treatments, typically clothianidin or thiamethoxam, are routinely applied to >80% of maize (corn) seed grown in North America where they are marketed as a targeted pesticide delivery system. Despite this widespread use, the amount of compound translocated into plant tissue from the initial seed treatment to provide protection has not been reported. Our two year field study compared concentrations of clothianidin seed treatments in maize to that of maize without neonicotinoid seed treatments and found neonicotinoids present in root tissues up to 34 days post planting. Plant-bound clothianidin concentrations followed an exponential decay pattern with initially high values followed by a rapid decrease within the first ~20 days post planting. A maximum of 1.34% of the initial seed treatment was successfully recovered from plant tissues in both study years and a maximum of 0.26% was recovered from root tissue. Our findings show neonicotinoid seed treatments may provide protection from some early season secondary maize pests. However, the proportion of the neonicotinoid seed treatment clothianidin translocated into plant tissues throughout the growing season is low overall and this observation may provide a mechanism to explain reports of inconsistent efficacy of this pest management approach and increasing detections of environmental neonicotinoids. PMID:28282441

Organic Compounds and Trace Elements in Fish Tissue and Bed Sediment in the Delaware River Basin, New Jersey, Pennsylvania, New York, and Delaware, 1998-2000

USGS Publications Warehouse

Romanok, Kristin M.; Fischer, Jeffrey M.; Riva-Murray, Karen; Brightbill, Robin; Bilger, Michael

2006-01-01

As part of the National Water-Quality Assessment (NAWQA) program activities in the Delaware River Basin (DELR), samples of fish tissue from 21 sites and samples of bed sediment from 35 sites were analyzed for a suite of organic compounds and trace elements. The sampling sites, within subbasins ranging in size from 11 to 600 square miles, were selected to represent 5 main land-use categories in the DELR -forest, low-agricultural, agricultural, urban, and mixed use. Samples of both fish tissue and bed sediment were also collected from 4 'large-river' sites that represented drainage areas ranging from 1,300 to 6,800 square miles, areas in which the land is used for a variety of purposes. One or more of the organochlorine compounds-DDT and chlordane metabolites, polychlorinated biphenyls (total PCBs), and dieldrin- were detected frequently in samples collected over a wide geographic area. One or more of these compounds were detected in fish-tissue samples from 92 percent of the sites and in bed-sediment samples from 82 percent of the sites. Concentrations of total DDT, total chlordanes, total PCBs, and dieldrin in whole white suckers and in bed sediment were significantly related to urban/industrial basin characteristics, such as percentage of urban land use and population density. Semi-volatile organic compounds (SVOCs)-total polycyclic aromatic hydrocarbons (PAHs), total phthalates, and phenols- were detected frequently in bed-sediment samples. All three types of SVOCs were detected in samples from at least one site in each land-use category. The highest detection rates and concentrations typically were in samples from sites in the urban and mixed land-use categories, as well as from the large-river sites. Concentrations of total PAHs and total phthalates in bed-sediment samples were found to be statistically related to percentages of urban land use and to population density in the drainage areas represented by the sampling sites. The samples of fish tissue and bed sediment collected throughout the DELR were analyzed for a large suite of trace elements, but results of the analyses for eight elements-arsenic, cadmium, chromium, copper, lead, nickel, mercury, and zinc- that are considered contaminants of concern are described in this report. One or more of the eight trace elements were detected in samples from every fish tissue and bed-sediment sampling site, and all of the trace elements were detected in samples from 97 percent of the bed-sediment sites. The concentrations of organic compounds and trace elements in the DELR samples were compared to applicable guidelines for the protection of wildlife and other biological organisms. Concentrations of total DDT, total chlordanes, total PCBs, and dieldrin in fish-tissue samples from 14 sites exceeded one or more of the Wildlife Protective Guidelines established by the New York State Department of Environmental Conservation. Concentrations of one or more organic compounds in samples from 16 bed-sediment sites exceeded the Threshold Effects Concentrations (TEC) of the Canadian Sediment Quality Guidelines, and concentrations of one or more of the eight trace elements in samples from 38 bed-sediment sites exceeded the TEC. (The TEC is the concentration below which adverse biological effects in freshwater ecosystems are expected to be rare.) Concentrations of organic compounds in samples from some bed-sediment sites exceeded the Canadian Probable Effects Concentrations (PEC), and concentrations of trace elements in samples from 18 sites exceeded the PEC. (The PEC is the concentration above which adverse effects to biological organisms are expected to occur frequently). Concentrations of organic compounds and trace elements in samples from the DELR were compared to similar data from other NAWQA study units in the northeastern United States and also data from the Mobile River (Alabama) Basin and the Northern Rockies Intermontane Basin study units. Median concentrations of to

Non-Nutrient, Naturally Occurring Phenolic Compounds with Antioxidant Activity for the Prevention and Treatment of Periodontal Diseases

PubMed Central

Varela-López, Alfonso; Bullón, Pedro; Giampieri, Francesca; Quiles, José L.

2015-01-01

One of the main factors able to explain the pathophysiological mechanism of inflammatory conditions that occur in periodontal disease is oxidative stress. Given the emerging understanding of this relationship, host-modulatory therapies using antioxidants could be interesting to prevent or slow the breakdown of soft and hard periodontal tissues. In this context, non-nutrient phenolic compounds of various foods and plants have received considerable attention in the last decade. Here, studies focusing on the relationship between different compounds of this type with periodontal disease have been collected. Among them, thymoquinone, coenzyme Q (CoQ), mangiferin, resveratrol, verbascoside and some flavonoids have shown to prevent or ameliorate periodontal tissues damage in animal models. However evidence regarding this effect in humans is poor and only limited to topical treatments with CoQ and catechins. Along with animal experiments, in vitro studies indicate that possible mechanisms by which these compounds might exert their protective effects include antioxidative properties, oxygen and nitrogen scavenging abilities, and also inhibitory effects on cell signaling cascades related to inflammatory processes which have an effect on RNS or ROS production as well as on antioxidant defense systems. PMID:26783837

Suppression of Coronary Atherosclerosis by Helix B Surface Peptide, a Nonerythropoietic, Tissue-Protective Compound Derived from Erythropoietin

PubMed Central

Ueba, Hiroto; Shiomi, Masashi; Brines, Michael; Yamin, Michael; Kobayashi, Tsutomu; Ako, Junya; Momomura, Shin-ichi; Cerami, Anthony; Kawakami, Masanobu

2013-01-01

Erythropoietin (EPO), a type I cytokine originally identified for its critical role in hematopoiesis, has been shown to have nonhematopoietic, tissue-protective effects, including suppression of atherosclerosis. However, prothrombotic effects of EPO hinder its potential clinical use in nonanemic patients. In the present study, we investigated the antiatherosclerotic effects of helix B surface peptide (HBSP), a nonerythropoietic, tissue-protective compound derived from EPO, by using human umbilical vein endothelial cells (HUVECs) and human monocytic THP-1 cells in vitro and Watanabe heritable hyperlipidemic spontaneous myocardial infarction (WHHLMI) rabbits in vivo. In HUVECs, HBSP inhibited apoptosis (≈70%) induced by C-reactive protein (CRP), a direct mediator of atherosclerosis. By using a small interfering RNA approach, Akt was shown to be a key molecule in HBSP-mediated prevention of apoptosis. HBSP also attenuated CRP-induced production of tumor necrosis factor (TNF)-α and matrix metalloproteinase-9 in THP-1 cells. In the WHHLMI rabbit, HBSP significantly suppressed progression of coronary atherosclerotic lesions as assessed by mean cross-sectional stenosis (HBSP 21.3 ± 2.2% versus control peptide 38.0 ± 2.7%) and inhibited coronary artery endothelial cell apoptosis with increased activation of Akt. Furthermore, TNF-α expression and the number of M1 macrophages and M1/M2 macrophage ratio in coronary atherosclerotic lesions were markedly reduced in HBSP-treated animals. In conclusion, these data demonstrate that HBSP suppresses coronary atherosclerosis, in part by inhibiting endothelial cell apoptosis through activation of Akt and in association with decreased TNF-α production and modified macrophage polarization in coronary atherosclerotic lesions. Because HBSP does not have the prothrombotic effects of EPO, our study may provide a novel therapeutic strategy that prevents progression of coronary artery disease. PMID:23648638

Impact of Endophytic Microorganisms on Plants, Environment and Humans

PubMed Central

Nair, Dhanya N.; Padmavathy, S.

2014-01-01

Endophytes are microorganisms (bacteria or fungi or actinomycetes) that dwell within robust plant tissues by having a symbiotic association. They are ubiquitously associated with almost all plants studied till date. Some commonly found endophytes are those belonging to the genera Enterobacter sp., Colletotrichum sp., Phomopsis sp., Phyllosticta sp., Cladosporium sp., and so forth. Endophytic population is greatly affected by climatic conditions and location where the host plant grows. They produce a wide range of compounds useful for plants for their growth, protection to environmental conditions, and sustainability, in favour of a good dwelling place within the hosts. They protect plants from herbivory by producing certain compounds which will prevent animals from further grazing on the same plant and sometimes act as biocontrol agents. A large amount of bioactive compounds produced by them not only are useful for plants but also are of economical importance to humans. They serve as antibiotics, drugs or medicines, or the compounds of high relevance in research or as compounds useful to food industry. They are also found to have some important role in nutrient cycling, biodegradation, and bioremediation. In this review, we have tried to comprehend different roles of endophytes in plants and their significance and impacts on man and environment. PMID:24587715

Compound C inhibits macrophage chemotaxis through an AMPK-independent mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Youngyi; Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Jeonbuk 54896; Park, Byung-Hyun, E-mail: bhpark@jbnu.ac.kr

Macrophage infiltration in adipose tissue is a well-established cause of obesity-linked insulin resistance. AMP-activated protein kinase (AMPK) activation in peripheral tissues such as adipose tissue has beneficial effects on the protection against obesity-induced insulin resistance, which is mainly mediated by prevention of adipose tissue macrophage infiltration and inflammation. In examining the role of AMPK on adipose tissue inflammation, we unexpectedly found that compound C (CC), despite its inhibition of AMPK, robustly inhibited macrophage chemotaxis in RAW 264.7 cells when adipocyte conditioned medium (CM) was used as a chemoattractant. Here, we report that CC inhibition of macrophage migration occurred independently ofmore » AMPK. Mechanistically, this inhibitory effect of cell migration by CC was mediated by inhibition of the focal adhesion kinase, AKT, nuclear factor κB pathways. Moreover, the expression of chemokine monocyte chemoattractant protein-1 and pro-inflammatory genes such as tumor necrosis factor α and inducible nitric oxide synthase were prevented by CC treatment in RAW 264.7 cells stimulated with either adipocyte CM or lipopolysaccharide. Lastly, in accord with the findings of the anti-inflammatory effect of CC, we demonstrated that CC functioned as a repressor of macrophage CM-mediated insulin resistance in adipocytes. Taken together, our results suggest that CC serves as a useful inhibitory molecule against macrophage chemotaxis into adipose tissue and thus might have therapeutic potential for the treatment of obesity-linked adipose inflammation. - Highlights: • Compound C (CC) inhibits macrophage chemotaxis regardless of AMPK suppression. • CC enhances insulin sensitivity in adipocytes. • CC inhibits focal adhesion kinase, AKT, and NF-κB signaling in RAW 264.7 cells.« less

Antioxidants Mediate Both Iron Homeostasis and Oxidative Stress.

PubMed

Imam, Mustapha Umar; Zhang, Shenshen; Ma, Jifei; Wang, Hao; Wang, Fudi

2017-06-28

Oxidative stress is a common denominator in the pathogenesis of many chronic diseases. Therefore, antioxidants are often used to protect cells and tissues and reverse oxidative damage. It is well known that iron metabolism underlies the dynamic interplay between oxidative stress and antioxidants in many pathophysiological processes. Both iron deficiency and iron overload can affect redox state, and these conditions can be restored to physiological conditions using iron supplementation and iron chelation, respectively. Similarly, the addition of antioxidants to these treatment regimens has been suggested as a viable therapeutic approach for attenuating tissue damage induced by oxidative stress. Notably, many bioactive plant-derived compounds have been shown to regulate both iron metabolism and redox state, possibly through interactive mechanisms. This review summarizes our current understanding of these mechanisms and discusses compelling preclinical evidence that bioactive plant-derived compounds can be both safe and effective for managing both iron deficiency and iron overload conditions.

Antioxidants Mediate Both Iron Homeostasis and Oxidative Stress

PubMed Central

Zhang, Shenshen; Ma, Jifei; Wang, Hao; Wang, Fudi

2017-01-01

Oxidative stress is a common denominator in the pathogenesis of many chronic diseases. Therefore, antioxidants are often used to protect cells and tissues and reverse oxidative damage. It is well known that iron metabolism underlies the dynamic interplay between oxidative stress and antioxidants in many pathophysiological processes. Both iron deficiency and iron overload can affect redox state, and these conditions can be restored to physiological conditions using iron supplementation and iron chelation, respectively. Similarly, the addition of antioxidants to these treatment regimens has been suggested as a viable therapeutic approach for attenuating tissue damage induced by oxidative stress. Notably, many bioactive plant-derived compounds have been shown to regulate both iron metabolism and redox state, possibly through interactive mechanisms. This review summarizes our current understanding of these mechanisms and discusses compelling preclinical evidence that bioactive plant-derived compounds can be both safe and effective for managing both iron deficiency and iron overload conditions. PMID:28657578

Pesticides and PCBs in sediments and fish from the Salton Sea, California, USA.

PubMed

Sapozhnikova, Yelena; Bawardi, Ola; Schlenk, Daniel

2004-05-01

The Salton Sea, the largest manmade lake in California, is officially designated by the State of California as an agricultural drainage reservoir. The purpose of this study was to determine organochlorine and organophosphorous pesticides, as well as polychlorinated biphenyl (PCB) concentrations in sediments and fish tissues in the Salton Sea and evaluate the relative ecological risk of these compounds. Sediment samples were taken during 2000-2001 and fish tissues (Tilapia mossambique, Cynoscion xanthulu) were collected in May 2001. All samples were analyzed for 12 chlorinated pesticides, 6 organophosphorus pesticides, and 55 polychlorinated biphenyl (PCB) congeners. SigmaDichlorodiphenyltrichloroethane (SigmaDDT) and total PCB concentrations observed in sediments ranged from 10 to 40 and 116 to 304 ng/g dry wt, respectively. DDT/DDD ratios in sediments and fish tissues of the northern Sea in 2001 indicated recent DDT exposure. Lindane, dieldrin, dichlorodiphenylethane (DDE) and total PCB concentrations detected in sediments exceeded probable effect levels established for freshwater ecosystems, and pp-DDE and total PCB concentrations were higher than effect range-median values developed for marine and estuarine sediments. In fish liver, concentrations of endrin and SigmaDDT exceeded threshold effect level established for invertebrates. SigmaDDT concentrations detected in fish tissues were higher than threshold concentrations for the protection of wildlife consumers of aquatic biota. DDE concentrations in fish muscles tissues were above the 50 ng/g concentration threshold for the protection of predatory birds. Dimethoate, diazinon, malathion, chlorpyrifos, disulfoton varied from < or = 0.15 to 9.5 ng/g dry wt in sediments and from < or = 0.1 to 80.3 ng/g wet wt in fish tissues. Disulfoton was found in relatively high concentrations (up to 80.3 ng/g) in all organs from Tilapia and Corvina. These results demonstrate continued contamination of specific organochlorine compounds in sediments and resident fish species of the Salton Sea.

Trace elements and organic compounds in streambed sediment and fish tissue of coastal New England streams, 1998-99

USGS Publications Warehouse

Chalmers, Ann

2002-01-01

Streambed sediment and fish tissue were collected at 14 river sites in eastern New England during low-flow conditions in 1998 and 1999 as part of the New England Coastal Basins (NECB) study of the U.S. Geological Survey National Water-Quality Assessment (NAWQA) Program. Sampling sites were selected over a range of urban settings. Population densities at selected sites ranged from 26 to 3,585 people per square mile, and urban land use ranged from 1 to 68 percent. The streambed sediment samples were analyzed for a total of 141 contaminants, including 45 trace elements, 32 organochlorine compounds, and 64 semi-volatile organic compounds. The fish tissue samples were analyzed for 22 trace elements and 28 organochlorine compounds. Concentrations of selected contaminants in both streambed sediment and fish tissue correlated more strongly with population density than with other watershed characteristics. Cadmium, copper, lead, mercury, zinc, total polycyclic aromatic hydrocarbons (PAHs), total polychlorinated biphenyls (PCBs), dichloro diphenyl trichloroethane and metabolites (DDTM), and total chlordane in streambed sediment all showed strong positive correlations with population density (rho = 0.71 to 0.85, p value = 0.005 to <0.001). Correlations between population density and selected contaminants in fish tissue were less significant than with streambed sediment (rho = 0.62 to 0.72, p value = 0.03 to 0.008). Organic carbon concentrations were correlated with concentrations of arsenic, selenium, total PAHs, total PCBs, and DDTM in streambed sediment. The relation between concentrations of contaminants in streambed sediment and fish tissue was stronger for organochlorine compounds (rho = 0.75 to 0.55, p = 0.005 to 0.065) than for trace elements (rho = 0.63 to 0.53, p = 0.029 to 0.069). The NECB study area had the highest median concentrations of lead, mercury, total PAHs, total PCBs, and DDTM in streambed sediment and the highest median concentration of PCBs in fish tissue compared to 45 other NAWQA study units across the Nation. Concentrations of many of these constituents in streambed sediment also were frequently above the consensus-based Sediment-Quality Guidelines for the protection of wildlife, suggesting they are a threat to the health of aquatic biota in New England.

Body protective compound-157 enhances alkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro

PubMed Central

Huang, Tonglie; Zhang, Kuo; Sun, Lijuan; Xue, Xiaochang; Zhang, Cun; Shu, Zhen; Mu, Nan; Gu, Jintao; Zhang, Wangqian; Wang, Yukun; Zhang, Yingqi; Zhang, Wei

2015-01-01

Chemical burns take up a high proportion of burns admissions and can penetrate deep into tissues. Various reagents have been applied in the treatment of skin chemical burns; however, no optimal reagent for skin chemical burns currently exists. The present study investigated the effect of topical body protective compound (BPC)-157 treatment on skin wound healing, using an alkali burn rat model. Topical treatment with BPC-157 was shown to accelerate wound closure following an alkali burn. Histological examination of skin sections with hematoxylin–eosin and Masson staining showed better granulation tissue formation, reepithelialization, dermal remodeling, and a higher extent of collagen deposition when compared to the model control group on the 18th day postwounding. BPC-157 could promote vascular endothelial growth factor expression in wounded skin tissues. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and cell cycle analysis demonstrated that BPC-157 enhanced the proliferation of human umbilical vein endothelial cells (HUVECs). Transwell assay and wound healing assay showed that BPC-157 significantly promoted migration of HUVECs. We also observed that BPC-157 upregulated the expression of VEGF-a and accelerated vascular tube formation in vitro. Moreover, further studies suggested that BPC-157 regulated the phosphorylation level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) as well as its downstream targets, including c-Fos, c-Jun, and Egr-1, which are key molecules involved in cell growth, migration, and angiogenesis. Altogether, our results indicated that BPC-157 treatment may accelerate wound healing in a model of alkali burn-induced skin injury. The therapeutic mechanism may be associated with accelerated granulation tissue formation, reepithelialization, dermal remodeling, and collagen deposition through ERK1/2 signaling pathway. PMID:25995620

Body protective compound-157 enhances alkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro.

PubMed

Huang, Tonglie; Zhang, Kuo; Sun, Lijuan; Xue, Xiaochang; Zhang, Cun; Shu, Zhen; Mu, Nan; Gu, Jintao; Zhang, Wangqian; Wang, Yukun; Zhang, Yingqi; Zhang, Wei

2015-01-01

Chemical burns take up a high proportion of burns admissions and can penetrate deep into tissues. Various reagents have been applied in the treatment of skin chemical burns; however, no optimal reagent for skin chemical burns currently exists. The present study investigated the effect of topical body protective compound (BPC)-157 treatment on skin wound healing, using an alkali burn rat model. Topical treatment with BPC-157 was shown to accelerate wound closure following an alkali burn. Histological examination of skin sections with hematoxylin-eosin and Masson staining showed better granulation tissue formation, reepithelialization, dermal remodeling, and a higher extent of collagen deposition when compared to the model control group on the 18th day postwounding. BPC-157 could promote vascular endothelial growth factor expression in wounded skin tissues. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and cell cycle analysis demonstrated that BPC-157 enhanced the proliferation of human umbilical vein endothelial cells (HUVECs). Transwell assay and wound healing assay showed that BPC-157 significantly promoted migration of HUVECs. We also observed that BPC-157 upregulated the expression of VEGF-a and accelerated vascular tube formation in vitro. Moreover, further studies suggested that BPC-157 regulated the phosphorylation level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) as well as its downstream targets, including c-Fos, c-Jun, and Egr-1, which are key molecules involved in cell growth, migration, and angiogenesis. Altogether, our results indicated that BPC-157 treatment may accelerate wound healing in a model of alkali burn-induced skin injury. The therapeutic mechanism may be associated with accelerated granulation tissue formation, reepithelialization, dermal remodeling, and collagen deposition through ERK1/2 signaling pathway.

Arbuscular Mycorrhizal Fungi and Plant Chemical Defence: Effects of Colonisation on Aboveground and Belowground Metabolomes.

PubMed

Hill, Elizabeth M; Robinson, Lynne A; Abdul-Sada, Ali; Vanbergen, Adam J; Hodge, Angela; Hartley, Sue E

2018-02-01

Arbuscular mycorrhizal fungal (AMF) colonisation of plant roots is one of the most ancient and widespread interactions in ecology, yet the systemic consequences for plant secondary chemistry remain unclear. We performed the first metabolomic investigation into the impact of AMF colonisation by Rhizophagus irregularis on the chemical defences, spanning above- and below-ground tissues, in its host-plant ragwort (Senecio jacobaea). We used a non-targeted metabolomics approach to profile, and where possible identify, compounds induced by AMF colonisation in both roots and shoots. Metabolomics analyses revealed that 33 compounds were significantly increased in the root tissue of AMF colonised plants, including seven blumenols, plant-derived compounds known to be associated with AMF colonisation. One of these was a novel structure conjugated with a malonyl-sugar and uronic acid moiety, hitherto an unreported combination. Such structural modifications of blumenols could be significant for their previously reported functional roles associated with the establishment and maintenance of AM colonisation. Pyrrolizidine alkaloids (PAs), key anti-herbivore defence compounds in ragwort, dominated the metabolomic profiles of root and shoot extracts. Analyses of the metabolomic profiles revealed an increase in four PAs in roots (but not shoots) of AMF colonised plants, with the potential to protect colonised plants from below-ground organisms.

Characterization of the quality of water, bed sediment, and fish in Mittry Lake, Arizona, 2014–15

USGS Publications Warehouse

Hermosillo, Edyth; Coes, Alissa L.

2017-03-01

Water, bed-sediment, and fish sampling was conducted in Mittry Lake, Arizona, in 2014–15 to establish current water-quality conditions of the lake. The parameters of temperature, dissolved-oxygen concentration, specific conductance, and alkalinity were measured in the field. Water samples were collected and analyzed for dissolved major ions, dissolved trace elements, dissolved nutrients, dissolved organic carbon, dissolved pesticides, bacteria, and suspended-sediment concentrations. Bed-sediment and fish samples were analyzed for trace elements, halogenated compounds, total mercury, and methylmercury.U.S. Environmental Protection Agency secondary maximum contaminant levels in drinking water were exceeded for sulfate, chloride, and manganese in the water samples. Trace-element concentrations were relatively similar between the inlet, middle, and outlet locations. Concentrations for nutrients in all water samples were below the Arizona Department of Environmental Quality’s water-quality standards for aquatic and wildlife uses, and all bacteria levels were below the Arizona Department of Environmental Quality’s recommended recreational water-quality criteria. Three out of 81 pesticides were detected in the water samples.Trace-element concentrations in bed sediment were relatively consistent between the inlet, middle, and outlet locations. Lead, manganese, nickel, and zinc concentrations, however, decreased from the inlet to outlet locations. Concentrations for lead, nickel, and zinc in some bed-sediment samples exceeded consensus-based sediment-quality guidelines probable effect concentrations. Eleven out of 61 halogenated compounds were detected in bed sediment at the inlet location, whereas three were detected at the middle location, and five were detected at the outlet location. No methylmercury was detected in bed sediment. Total mercury was detected in bed sediment at concentrations below the consensus-based sediment-quality guidelines probable effect concentration.Sixteen trace elements were detected in at least one of the fish-tissue samples, and trace-element concentrations were relatively consistent between the three fish-tissue samples. Seven halogenated compounds were detected in at least one of the whole-body fish samples; four to five compounds were detected in each fish. One fish-tissue sample exceeded the U.S. Environmental Protection Agency human health consumption criteria for methylmercury.

Organochlorine compounds in bed sediment and fish tissue in the South Platte River Basin, USA, 1992-1993

USGS Publications Warehouse

Tate, C.M.; Heiny, J.S.

1996-01-01

Bed-sediment and fish-tissue samples were collected in the South Platte River Basin to determine the occurrence and distribution of organochlorine compounds in the basin. During August-November 1992 and August 1993, bed sediment (23 sites) and fish tissue (subset of 19 sites) were sampled and analyzed for 32 organochlorine compounds in bed sediment and 27 compounds in fish tissue. More types of organochlorine compounds were detected in fish tissue than in bed sediment. Total DDT, p,p???-DDE, o,p???-DDE, p,p???-DDD, total PCS, Dacthal??, dieldrin, cis-chlordane, cis-nonachlor, trans-nonachlor, and p,p???-DDT were detected in fish tissue at >25% of the sites; p,p???-DDE, total DDT, cis-chlordane, and trans-chlordane were detected in bed sediment at >25% of the sites. Organochlorine concentrations in bed sediment and fish tissue were related to land-use settings. Few organochlorine compounds were detected at minimally impacted sites located in rangeland, forest, and built-up land-use settings. Chlordane-related compounds and p,p???-methoxychlor in bed sediment and fish tissue, endrin in fish tissue, and endosulfan I in bed sediment were associated with urban and mixed (urban and agricultural) sites. Dacthal?? in bed sediment and fish tissue was associated with agricultural sites. The compounds HCB, ??-HCH, PCA, and toxaphene were detected only at mixed land-use sites. Although DDT and DDT-metabolites, dieldrin, and total PCB were detected in urban, mixed, and agricultural land-use settings, highest mean concentrations were detected at mixed land-use sites. Mixed land-use sites had the greatest number of organochlorine compounds detected in fish tissue, whereas urban and mixed sites had the greatest number of organochlorine compounds detected in bed sediment. Measuring concentrations of organochlorine compounds in bed sediment and fish tissue at the same site offers a more complete picture of the persistence of organochlorine compounds in the environment and their relation to land-use settings.

Occurrence of selected contaminants in water, fish tissue, and streambed sediments in central Nebraska, 1992-95

USGS Publications Warehouse

Frenzel, Steven A.

1996-01-01

Surface and ground water in Nebraska may contain contaminants resulting from human activities. For purposes of this publication, a contaminant is any element or compound whose presence may affect the water's suitability for certain uses. For example, herbicide concentrations may exceeed the U.S. Environmental Protection Agency's (USEPA) Health Advisory Levels (HAL) for drinking water or trace-element concentrations may exceed guidelines for the protection of aquatic life. In general, the contaminats discussed in this report enter the aquatic system through nonpoint-source runoff from agricultural lands that dominate the Nebraska landscape. However,because this assessment was conducted as part of a larger, national program, a screening for contaminants with non-agricultural origins was included.The measurement of water quality involves a variety of steps, each contributing unique information while also aggregating to an overall assessment. One aspect of water-quality assesment is to describe the occurrence and distribution of contaminants. Some contaminants may be hundreds or thousands of times more concentrated in the tissues of aquatic organisms or in fine sediments than they are in the water. As a result, fish tissue and streambed sediments are well suited for the detection of certain contaminants. For example, pesticides used in the United States prior to the early 1970's, such as DDT, may have degraded into more stable but still toxic compounds that are highly concentrated in fish tissues. Conversely, other contaminants are not concentrated in sediments or tissues but are readily detected in water samples. Organonitrogen herbicides (such as atrazine), the most commonly used herbicides in Nebraska, are examples of water-soluble contaminants.Several sampling strategies were used to address specific questions. Some sites were sampled repeatedly through time and during all hydrologic conditions, whereas others were sampled only once to determine presence of contaminants. Because a strong relation between concentration and streamflow often exists for contaminants originating from nonpoint sources, streams typically were sampled near gaging stations that monitor streamflow.

The widespread plant-colonizing bacterial species Pseudomonas syringae detects and exploits an extracellular pool of choline in hosts.

PubMed

Chen, Chiliang; Li, Shanshan; McKeever, Dana R; Beattie, Gwyn A

2013-09-01

The quaternary ammonium compound (QAC) choline is a major component of membrane lipids in eukaryotes and, if available to microbial colonists of plants, could provide benefits for growth and protection from stress. Free choline is found in homogenized plant tissues, but its subcellular location and availability to plant microbes are not known. Whole-cell bacterial bioreporters of the phytopathogen Pseudomonas syringae were constructed that couple a QAC-responsive transcriptional fusion with well-characterized bacterial QAC transporters. These bioreporters demonstrated the presence of abundant free choline compounds released from germinating seeds and seedlings of the bean Phaseolus vulgaris, and a smaller but consistently detectable amount of QACs, probably choline, from leaves. The localization of P. syringae bioreporter cells to the surface and intercellular sites of plant tissues demonstrated the extracellular location of these QAC pools. Moreover, P. syringae mutants that were deficient in the uptake of choline compounds exhibited reduced fitness on leaves, highlighting the importance of extracellular choline to P. syringae on leaves. Our data support a model in which this choline pool is derived from the phospholipid phosphatidylcholine through plant-encoded phospholipases that release choline into the intercellular spaces of plant tissues, such as for membrane lipid recycling. The consequent extracellular release of choline compounds enables their interception and exploitation by plant-associated microbes, and thus provides a selective advantage for microbes such as P. syringae that are adapted to maximally exploit choline. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

CLOSED-LOOP STRIPPING ANALYSIS (CLSA) OF SYNTHETIC MUSK COMPOUNDS FROM FISH TISSUES WITH MEASUREMENT BY GAS CHROMATOGRAPHY-MASS SPECTROMETRY WITH SELECTED-ION MONITORING

EPA Science Inventory

Synthetic musk compounds have been found in surface water, fish tissues, and human breast milk. Current techniques for separating these compounds from fish tissues require tedious sample clean-upprocedures A simple method for the deterrnination of these compounds in fish tissues ...

[EFFECT OF PYRETHROIDS ON TAIGA TICKS (IXODES PERSULCATUS IXODIDAE)].

PubMed

Germant, O M; Shashina, N I

2016-01-01

Nonspecific prevention of infections, the agents of which are transmitted by Ixodes ticks, is aimed at stopping the suction of the ticks to humans and is substantially based one the use of acaricides. The most interesting group of compounds to be used to individually protect humans is pyrethroids that cause different nerve conduction disturbances in the ticks, which result in their paralysis and death more significantly rapidly than the compounds from other chemical groups. The effect of 8 pyrethroids was investigated when the taiga ticks were in contact with the tissue treated with the compounds. The relationship of the chemical structure of pyrethroids with their acaricidal activity was analyzed from motor activity values and knockdown time. The test pyreithroids, in order of decreasing acaricidal activity, are imiprothrin cyphenothrin, cyfluthrin, alpha-cyperamethrin, zeta-cyperimethrin fenothrin, flumethrin.

Nuclear Shield: A Multi-Enzyme Task-Force for Nucleus Protection

PubMed Central

Pallottini, Valentina; Canuti, Lorena; De Canio, Michele; Urbani, Andrea; Marzano, Valeria; Cornetta, Tommaso; Stano, Pasquale; Giovanetti, Anna; Stella, Lorenzo; Canini, Antonella; Federici, Giorgio; Ricci, Giorgio

2010-01-01

Background In eukaryotic cells the nuclear envelope isolates and protects DNA from molecules that could damage its structure or interfere with its processing. Moreover, selected protection enzymes and vitamins act as efficient guardians against toxic compounds both in the nucleoplasm and in the cytosol. The observation that a cytosolic detoxifying and antioxidant enzyme i.e. glutathione transferase is accumulated in the perinuclear region of the rat hepatocytes suggests that other unrecognized modalities of nuclear protection may exist. Here we show evidence for the existence of a safeguard enzyme machinery formed by an hyper-crowding of cationic enzymes and proteins encompassing the nuclear membrane and promoted by electrostatic interactions. Methodology/Principal Findings Electron spectroscopic imaging, zeta potential measurements, isoelectrofocusing, comet assay and mass spectrometry have been used to characterize this surprising structure that is present in the cells of all rat tissues examined (liver, kidney, heart, lung and brain), and that behaves as a “nuclear shield”. In hepatocytes, this hyper-crowding structure is about 300 nm thick, it is mainly formed by cationic enzymes and the local concentration of key protection enzymes, such as glutathione transferase, catalase and glutathione peroxidase is up to seven times higher than in the cytosol. The catalytic activity of these enzymes, when packed in the shield, is not modified and their relative concentrations vary remarkably in different tissues. Removal of this protective shield renders chromosomes more sensitive to damage by oxidative stress. Specific nuclear proteins anchored to the outer nuclear envelope are likely involved in the shield formation and stabilization. Conclusions/Significance The characterization of this previously unrecognized nuclear shield in different tissues opens a new interesting scenario for physiological and protection processes in eukaryotic cells. Selection and accumulation of protection enzymes near sensitive targets represents a new safeguard modality which deeply differs from the adaptive response which is based on expression of specific enzymes. PMID:21170318

Neuroprotection by Delta9-tetrahydrocannabinol, the main active compound in marijuana, against ouabain-induced in vivo excitotoxicity.

PubMed

van der Stelt, M; Veldhuis, W B; Bär, P R; Veldink, G A; Vliegenthart, J F; Nicolay, K

2001-09-01

Excitotoxicity is a paradigm used to explain the biochemical events in both acute neuronal damage and in slowly progressive, neurodegenerative diseases. Here, we show in a longitudinal magnetic resonance imaging study that Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the main active compound in marijuana, reduces neuronal injury in neonatal rats injected intracerebrally with the Na(+)/K(+)-ATPase inhibitor ouabain to elicit excitotoxicity. In the acute phase Delta(9)-THC reduced the volume of cytotoxic edema by 22%. After 7 d, 36% less neuronal damage was observed in treated rats compared with control animals. Coadministration of the CB(1) cannabinoid receptor antagonist SR141716 prevented the neuroprotective actions of Delta(9)-THC, indicating that Delta(9)-THC afforded protection to neurons via the CB(1) receptor. In Delta(9)-THC-treated rats the volume of astrogliotic tissue was 36% smaller. The CB(1) receptor antagonist did not block this effect. These results provide evidence that the cannabinoid system can serve to protect the brain against neurodegeneration.

Cardiac HDAC6 Catalytic Activity is Induced in Response to Chronic Hypertension

PubMed Central

Lemon, Douglas D.; Horn, Todd R.; Cavasin, Maria A.; Jeong, Mark Y.; Haubold, Kurt W.; Long, Carlin S.; Irwin, David C.; McCune, Sylvia A.; Chung, Eunhee; Leinwand, Leslie A.; McKinsey, Timothy A.

2011-01-01

Small molecule histone deacetylase (HDAC) inhibitors block adverse cardiac remodeling in animal models of heart failure. The efficacious compounds target class I, class IIb and, to a lesser extent, class IIa HDACs. It is hypothesized that a selective inhibitor of a specific HDAC class (or an isoform within that class) will provide a favorable therapeutic window for the treatment of heart failure, although the optimal selectivity profile for such a compound remains unknown. Genetic studies have suggested that class I HDACs promote pathological cardiac remodeling, while class IIa HDACs are protective. In contrast, nothing is known about the function or regulation of class IIb HDACs in the heart. We developed assays to quantify catalytic activity of distinct HDAC classes in left and right ventricular cardiac tissue from animal models of hypertensive heart disease. Class I and IIa HDAC activity was elevated in some but not all diseased tissues. In contrast, catalytic activity of the class IIb HDAC, HDAC6, was consistently increased in stressed myocardium, but not in a model of physiologic hypertrophy. HDAC6 catalytic activity was also induced by diverse extracellular stimuli in cultured cardiac myocytes and fibroblasts. These findings suggest an unforeseen role for HDAC6 in the heart, and highlight the need for pre-clinical evaluation of HDAC6-selective inhibitors to determine whether this HDAC isoform is pathological or protective in the setting of cardiovascular disease. PMID:21539845

BitterDB: a database of bitter compounds

PubMed Central

Wiener, Ayana; Shudler, Marina; Levit, Anat; Niv, Masha Y.

2012-01-01

Basic taste qualities like sour, salty, sweet, bitter and umami serve specific functions in identifying food components found in the diet of humans and animals, and are recognized by proteins in the oral cavity. Recognition of bitter taste and aversion to it are thought to protect the organism against the ingestion of poisonous food compounds, which are often bitter. Interestingly, bitter taste receptors are expressed not only in the mouth but also in extraoral tissues, such as the gastrointestinal tract, indicating that they may play a role in digestive and metabolic processes. BitterDB database, available at http://bitterdb.agri.huji.ac.il/bitterdb/, includes over 550 compounds that were reported to taste bitter to humans. The compounds can be searched by name, chemical structure, similarity to other bitter compounds, association with a particular human bitter taste receptor, and so on. The database also contains information on mutations in bitter taste receptors that were shown to influence receptor activation by bitter compounds. The aim of BitterDB is to facilitate studying the chemical features associated with bitterness. These studies may contribute to predicting bitterness of unknown compounds, predicting ligands for bitter receptors from different species and rational design of bitterness modulators. PMID:21940398

H2S-releasing nanoemulsions: a new formulation to inhibit tumor cells proliferation and improve tissue repair

PubMed Central

Carotenuto, Felicia; Khashoggi, Haneen A.; Nanni, Francesca; Melino, Sonia

2016-01-01

The improvement of solubility and/or dissolution rate of poorly soluble natural compounds is an ideal strategy to make them optimal candidates as new potential drugs. Accordingly, the allyl sulfur compounds and omega-3 fatty acids are natural hydrophobic compounds that exhibit two important combined properties: cardiovascular protection and antitumor activity. Here, we have synthesized and characterized a novel formulation of diallyl disulfide (DADS) and α-linolenic acid (ALA) as protein-nanoemulsions (BAD-NEs), using ultrasounds. BAD-NEs are stable over time at room temperature and show antioxidant and radical scavenging property. These NEs are also optimal H2S slow-release donors and show a significant anti-proliferative effect on different human cancer cell lines: MCF-7 breast cancer and HuT 78 T-cell lymphoma cells. BAD-NEs are able to regulate the ERK1/2 pathway, inducing apoptosis and cell cycle arrest at the G0/G1 phase. We have also investigated their effect on cell proliferation of human adult stem/progenitor cells. Interestingly, BAD-NEs are able to improve the Lin– Sca1+ human cardiac progenitor cells (hCPC) proliferation. This stem cell growth stimulation is combined with the expression and activation of proteins involved in tissue-repair, such as P-AKT, α-sma and connexin 43. Altogether, our results suggest that these antioxidant nanoemulsions might have potential application in selective cancer therapy and for promoting the muscle tissue repair. PMID:27741519

Development of suspect and non-target screening methods for detection of organic contaminants in highway runoff and fish tissue with high-resolution time-of-flight mass spectrometry.

PubMed

Du, Bowen; Lofton, Jonathan M; Peter, Katherine T; Gipe, Alexander D; James, C Andrew; McIntyre, Jenifer K; Scholz, Nathaniel L; Baker, Joel E; Kolodziej, Edward P

2017-09-20

Untreated urban stormwater runoff contributes to poor water quality in receiving waters. The ability to identify toxicants and other bioactive molecules responsible for observed adverse effects in a complex mixture of contaminants is critical to effective protection of ecosystem and human health, yet this is a challenging analytical task. The objective of this study was to develop analytical methods using liquid chromatography coupled to high-resolution quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) to detect organic contaminants in highway runoff and in runoff-exposed fish (adult coho salmon, Oncorhynchus kisutch). Processing of paired water and tissue samples facilitated contaminant prioritization and aided investigation of chemical bioavailability and uptake processes. Simple, minimal processing effort solid phase extraction (SPE) and elution procedures were optimized for water samples, and selective pressurized liquid extraction (SPLE) procedures were optimized for fish tissues. Extraction methods were compared by detection of non-target features and target compounds (e.g., quantity and peak area), while minimizing matrix interferences. Suspect screening techniques utilized in-house and commercial databases to prioritize high-risk detections for subsequent MS/MS characterization and identification efforts. Presumptive annotations were also screened with an in-house linear regression (log K ow vs. retention time) to exclude isobaric compounds. Examples of confirmed identifications (via reference standard comparison) in highway runoff include ethoprophos, prometon, DEET, caffeine, cotinine, 4(or 5)-methyl-1H-methylbenzotriazole, and acetanilide. Acetanilide was also detected in runoff-exposed fish gill and liver samples. Further characterization of highway runoff and fish tissues (14 and 19 compounds, respectively with tentative identification by MS/MS data) suggests that many novel or poorly characterized organic contaminants exist in urban stormwater runoff and exposed biota.

Inhibition by blueberries (bilberries) and extract from milk thistle of rat forestomach hyperplasia induced by oral smokeless tobacco (Swedish snus).

PubMed

Nilsson, Robert; Mićić, Mileva; Filipović, Jelena; Šobot, Ana Valenta; Drakulić, Dunja; Stanojlović, Miloš; Joksiċ, Gordana

2016-04-01

The aim of this study was to identify palatable additives which have a significant protective action against soft tissue changes in the oral cavity caused by Swedish smokeless tobacco ("snus"), and that satisfy existing legal requirements. Although the cancer risk from snus is extremely low, long term use may result in highly undesirable keratotic lesions and associated epithelial abnormalities in the oral cavity. The rat forestomach, which is vulnerable to the irritative action of non-genotoxic compounds like butylated hydroxyanisole, propionic acid as well as snus, was chosen as an experimental model. Studied toxicological endpoints included histopathology and cellular proliferation based on DNA incorporation of bromodeoxyuridine. After 6 weeks' exposure, blueberries (bilberries) and an extract from the common milk thistle were found to exert a highly significant inhibition of cell proliferation induced by snus in the rat forestomach epithelium, indicating a potential protection with respect soft tissue changes in the human oral cavity. Copyright © 2016 Elsevier Inc. All rights reserved.

The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication

PubMed Central

Ouzzine, Mohamed; Gulberti, Sandrine; Ramalanjaona, Nick; Magdalou, Jacques; Fournel-Gigleux, Sylvie

2014-01-01

UDP-glucuronosyltransferases (UGTs) form a multigenic family of membrane-bound enzymes expressed in various tissues, including brain. They catalyze the formation of β-D-glucuronides from structurally unrelated substances (drugs, other xenobiotics, as well as endogenous compounds) by the linkage of glucuronic acid from the high energy donor, UDP-α-D-glucuronic acid. In brain, UGTs actively participate to the overall protection of the tissue against the intrusion of potentially harmful lipophilic substances that are metabolized as hydrophilic glucuronides. These metabolites are generally inactive, except for important pharmacologically glucuronides such as morphine-6-glucuronide. UGTs are mainly expressed in endothelial cells and astrocytes of the blood brain barrier (BBB). They are also associated to brain interfaces devoid of BBB, such as circumventricular organ, pineal gland, pituitary gland and neuro-olfactory tissues. Beside their key-role as a detoxication barrier, UGTs play a role in the steady-state of endogenous compounds, like steroids or dopamine (DA) that participate to the function of the brain. UGT isoforms of family 1A, 2A, 2B and 3A are expressed in brain tissues to various levels and are known to present distinct but overlapping substrate specificity. The importance of these enzyme species with regard to the formation of toxic, pharmacologically or physiologically relevant glucuronides in the brain will be discussed. PMID:25389387

Surface-water-quality assessment of the upper Illinois River Basin in Illinois, Indiana, and Wisconsin; pesticides and other synthetic organic compounds in water, sediment, and biota, 1975-90

USGS Publications Warehouse

Sullivan, Daniel J.; Stinson, Troy W.; Crawford, J. Kent; Schmidt, Arthur R.; Colman, John A.

1998-01-01

The distribution of pesticides and other synthetic organic compounds in water, sediment, and biota in the upper Illinois River Basin in Illinois, Indiana, and Wisconsin was examined from 1987 through 1990 as part of the pilot National Water-Quality Assesssment Program conducted by the U.S. Geological Survey. Historical data for water and sediment collected from 1975 through 1986 were similar to data collected from 1987 through 1990. Some compounds were detected in concentrations that exceed U.S. Environmental Protection Agency water-quality criteria. Results from pesticide sampling at four stations in 1988 and 1989 identified several agricultural pesticides that were detected more frequently and at higher concentrations in urban areas than in agricultural areas. Results from herbicide sampling at 17 stations in the Kankakee and Iroquois River Basins in 1990 indicated that atrazine concentrations exceeded the U.S. Environmental Protection Agency's maximum contaminant level for drinking water during runoff periods. Results from sampling for volatile and semivolatile organic compounds in water indicate that, with one exception, all stations at which more than one compound was detected were within 2 miles downstream from the nearest point source. Detections at two stations in the Chicago urban area accounted for 37 percent of the total number of detections. Concentrations of tetrachloroethylene, trichloroethylene, and 1,2-dichlorethane from stations in the Des Plaines River Basin exceeded the U.S. Environmental Protection Agency's maximum contaminant level for drinking water in one and two samples from the two stations in the Chicago area. Phenols and pentachlorophenols were detected most frequently in the Des Plaines River Basin where point-source discharges were common. Phenol concentrations were significantly different among the Des Plaines, Kankakee, and Fox River Basins. Phenols and pentachlorophenols never exceeded the general use and secondary contact standards. Results from a 1989 synoptic survey of semivolatile organic compounds in sediment indicate that these compounds were detected most frequently at sites in the Chicago urban area. Of the 17 stations at which 10 or more compounds were detected, 14 were located in the Des Plaines River subbasin, and 1 was on the Illinois River mainstem. As was the case with organic compounds in water, each of these sites was located within 2 miles downstream from point sources. Biota samples were collected and analyzed for organochlorines and polynuclear aromatic hydrocarbons in 1989 and 1990. The most commonly detected compound in both years was p,p'-DDE. National Academy of Science recommendations for chlordane and dieldrin for protection of predators were exceeded in 19 and 10 samples, respectively, when the 1989 and 1990 data were combined. In the nine fish-fillet samples collected in 1989, concentrations exceeded U.S. Environmental Protection Agency fish-tissue criteria in nine fillets for p,p'-DDE and five fillets for dieldrin.

Imaging with Mass Spectrometry of Bacteria on the Exoskeleton of Fungus-Growing Ants.

PubMed

Gemperline, Erin; Horn, Heidi A; DeLaney, Kellen; Currie, Cameron R; Li, Lingjun

2017-08-18

Mass spectrometry imaging is a powerful analytical technique for detecting and determining spatial distributions of molecules within a sample. Typically, mass spectrometry imaging is limited to the analysis of thin tissue sections taken from the middle of a sample. In this work, we present a mass spectrometry imaging method for the detection of compounds produced by bacteria on the outside surface of ant exoskeletons in response to pathogen exposure. Fungus-growing ants have a specialized mutualism with Pseudonocardia, a bacterium that lives on the ants' exoskeletons and helps protect their fungal garden food source from harmful pathogens. The developed method allows for visualization of bacterial-derived compounds on the ant exoskeleton. This method demonstrates the capability to detect compounds that are specifically localized to the bacterial patch on ant exoskeletons, shows good reproducibility across individual ants, and achieves accurate mass measurements within 5 ppm error when using a high-resolution, accurate-mass mass spectrometer.

Methylene Blue Partially Rescues Heart Defects in a Drosophila Model of Huntington's Disease.

PubMed

Heidari, Raheleh; Monnier, Véronique; Martin, Elodie; Tricoire, Hervé

2015-01-01

Huntington's disease (HD) is a Polyglutamine disease caused by the presence of CAG repeats in the first exon of Huntingtin (Htt), a large protein with multiple functions. In addition to neurodegeneration of specific brain regions, notably the striatum, HD also shows alterations in peripheral tissues, such as the heart, skeletal muscles or peripheral endocrine glands. Mutant Huntingtin (mHtt)-driven mitochondrial impairment may underlie some of the CNS and peripheral tissues dysfunctions, especially in tissues with high energy demand such as the heart. The aim of this study is to characterize two new inducible Drosophila HD heart models and to assay the therapeutic potential of methylene blue in these HD models. We report the construction of inducible Drosophila HD heart models, expressing two Nter fragments of the protein encompassing either exon 1 or the first 171 amino acids and the characterization of heart phenotypes in vivo. We show that both mHtt fragments are able to impair fly cardiac function with different characteristics. Additionally, expression of mHtt, which was limited to adulthood only, leads to mild heart impairment, as opposed to a strong and age-dependent phenotype observed when mHtt expression was driven during both developmental and adult stages. We report that treatment with methylene blue (MB), a protective compound in mitochondria-related diseases, partially protects the fly's heart against mHtt-induced toxicity, but does not rescue neuronal or glial phenotypes in other fly models of HD. This may be linked to its low penetration through the fly's blood-brain barrier. Our data suggest that improvement of mitochondrial function by MB, or related compounds, could be an efficient therapeutic strategy to prevent cardiac failure in HD patients.

Evaluation of the hepatoprotective effect of combination between hinokiflavone and Glycyrrhizin against CCl4 induced toxicity in rats.

PubMed

Abdel-Kader, Maged S; Abulhamd, Ashraf T; Hamad, Abubaker M; Alanazi, Abdullah H; Ali, Rizwan; Alqasoumi, Saleh I

2018-05-01

Liver diseases are one of the fatal syndromes due to the vital role of the liver. Most of the effective treatment of liver conditions are of natural origin. Silymarin (SI) is the standard drug used for treatment of impaired liver functions. Two natural compounds possessing promising liver protection and with different chemical structures namely; the bioflavonoid hinokiflavone (HF) isolated from Junipers phoenicea family Cupressaceae and the sweet saponin Glycyrrhizin (GL) present in  Glycyrrhiza glabra  (liquorice) were selected for the current study. Since the two compounds are of different nature, they may act by different mechanisms and express synergistic effect. Combination of the two compounds using to dose levels were challenged with single doses of HF, GL and SI as well. The comparison was monitored via measuring serum biochemical parameters including, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) and total bilirubin, tissue parameters such as MDA, NP-SH and TP, histopathological study using light and electron microscope. Protective effect on kidney was also monitored histopathologically and biochemically through observing the levels of LDH, creatinine, creatinine-kinase, urea and uric acid. The combinations of HF and GL showed protective effect more than the used single doses of HF and GL alone. However, SI was superior to the used combination in the two used doses in all the measured parameters. The liver and kidney cells appearance under normal and electron microscope showed that SI treated groups showed almost normal cells with slight toxic signs. Cells from group treated with the higher doses of the combination of HF and GL showed slight signs of intoxication under light and electron microscope indicating good level of protection. Although the combination of HF and GL expressed good protection in the higher dose, however, the combination did not exceed the protective effect of SI.

Mechanism of Prophylaxis by Silver Compounds against Infection of Burns

PubMed Central

Ricketts, C. R.; Lowbury, E. J. L.; Lawrence, J. C.; Hall, M.; Wilkins, M. D.

1970-01-01

To clarify tthe mechanism by which local application of silver compounds protects burns against infection, an ion-specific electrode was used to measùre the concentration of silver ions in solutions. By this method it was shown that in burn dressings silver ions were reduced to a very low level by precipitation as silver chloride. The antibacterial effect was found to depend on the availability of silver ions from solution in contact with precipitate. Between 10-5 and 10-6 molar silver nitrate solution in water was rapidly bactericidal. The minimal amount of silver nitrate causing inhibition of respiration of skin in tissue culture was about 25 times the minimal concentration of silver nitrate that inhibited growth of Pseudomonas aeruginosa. PMID:4986877

Disposition of toxic PCB congeners in snapping turtle eggs: expressed as toxic equivalents of TCDD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bryan, A.M.; Stone, W.B.; Olafsson, P.G.

1987-11-01

Studies of snapping turtles, taken from the region of the Upper Hudson River, in New York State, revealed exceedingly high levels of PCBs in the adipose tissue. There is evidence to suggest that large reserves of fat provide protection against chlorinated hydrocarbon toxicity. Such storage may protect snapping turtle eggs from disposition of toxic PCB congeners and account for the apparent absence of reports regarding detrimental effects on the hatchability of eggs from turtles living in the vicinity of the upper Hudson River. The present study was undertaken to determine if indeed these eggs are protected against disposition of toxicmore » PCB congeners by the presence of large reserves of fat. Although tissue volumes play an important role in determining the initial site of disposition, the major factor controlling the elimination of these compounds involves metabolism. For simple halogenated benzenes as well as for more complex halogenated biphenyls, oxidative metabolism catalyzed by P-448, occurs primarily at the site of two adjacent unsubstituted carbon atoms via arene oxide formation leading to the formation of water soluble metabolites. Toxicological studies have demonstrated that the most toxic PCB congeners, isosteriomers of tetrachlorodibenzo-p-dioxin (TCDD), require no metabolic activation. These compounds have chlorine atoms in the meta and para positions of both rings. It may be concluded that the structures of PCB congeners and isomers which favor induction of cytochrome P-448 are also those which are toxic and resist metabolism. It is the objective of the present study to determine if the heavy fat bodies of the female turtle provide a sufficiently large sink to retain the toxic congeners and prevent their incorporation into the eggs.« less

Photosynthetic capacity is negatively correlated with the concentration of leaf phenolic compounds across a range of different species.

PubMed

Sumbele, Sally; Fotelli, Mariangela N; Nikolopoulos, Dimosthenis; Tooulakou, Georgia; Liakoura, Vally; Liakopoulos, Georgios; Bresta, Panagiota; Dotsika, Elissavet; Adams, Mark A; Karabourniotis, George

2012-01-01

Phenolic compounds are the most commonly studied of all secondary metabolites because of their significant protective-defensive roles and their significant concentration in plant tissues. However, there has been little study on relationships between gas exchange parameters and the concentration of leaf phenolic compounds (total phenolics (TP) and condensed tannins (CT)) across a range of species. Therefore, we addressed the question: is there any correlation between photosynthetic capacity (A(max)) and TP and CT across species from different ecosystems in different continents? A plethora of functional and structural parameters were measured in 49 plant species following different growth strategies from five sampling sites located in Greece and Australia. The relationships between several leaf traits were analysed by means of regression and principal component analysis. The results revealed a negative relationship between TP and CT and A(max) among the different plant species, growth strategies and sampling sites, irrespective of expression (with respect to mass, area or nitrogen content). Principal component analysis showed that high concentrations of TP and CT are associated with thick, dense leaves with low nitrogen. This leaf type is characterized by low growth, A(max) and transpiration rates, and is common in environments with low water and nutrient availability, high temperatures and high light intensities. Therefore, the high TP and CT in such leaves are compatible with the protective and defensive functions ascribed to them. Our results indicate a functional integration between carbon gain and the concentration of leaf phenolic compounds that reflects the trade-off between growth and defence/protection demands, depending on the growth strategy adopted by each species.

Occurrence and Distribution of Organochlorine Compounds in Biological Tissue and Bed Sediment From Streams in the Trinity River Basin, Texas, 1992-93

USGS Publications Warehouse

Moring, J. Bruce

1997-01-01

This report describes the occurrence and distribution of organochlorine compounds in biological tissue and bed sediment from the Trinity River Basin study area of the National Water-Quality Assessment Program. Concentrations of organochlorine pesticides, polychlorinated biphenyls (PCBs), and other organochlorine compounds were determined in biological tissue and surficial bed sediment from 16 stream sites in the Trinity River Basin of east-central Texas. Asiatic clams (Corbicula fluminea) were collected at 10 sites, and fish, including blue catfish (Ictalurus furcatus), common carp (Cyprinus carpio), bluegill (Lepomis cyanellus), and yellow bullhead (Ameiurus natalis) were collected at all mainstem and two tributary sites. Thirty of the 36 compounds analyzed in biological tissue or surficial bed sediment were detected in one or both media. Overall, more organochlorine compounds were detected in bed sediment than in biological tissue; however, various chlordane isomers, DDT metabolites, and PCBs were detected more frequently in tissue than in sediment. The chlordane isomers and PCBs that were detected more frequently in biological tissue also were detected more frequently at urban sites than at agricultural sites. Organochlorine compound concentrations generally were highest in fish tissue from Trinity River mainstem sites. Fish tissue from the mainstem sites contained a higher percentage of lipids than did fish- and clam-tissue samples from the tributary sites.

Trace elements and organic compounds in sediment and fish tissue from the Great Salt Lake basins, Utah, Idaho, and Wyoming, 1998-99

USGS Publications Warehouse

Waddell, Kidd M.; Giddings, Elise M.

2004-01-01

A study to determine the occurrence and distribution of trace elements, organochlorine pesticides, polychlorinated biphenyls (PCBs), and semivolatile organic compounds in sediment and in fish tissue was conducted in the Great Salt Lake Basins study unit of the National Water-Quality Assessment (NAWQA) program during 1998-99. Streambed-sediment and fish-tissue samples were collected concurrently at 11 sites and analyzed for trace-element concentration. An additional four sites were sampled for streambed sediment only and one site for fish tissue only. Organic compounds were analyzed from streambed-sediment and fish-tissue samples at 15 sites concurrently.Bed-sediment cores from lakes, reservoirs, and Farmington Bay collected by the NAWQA program in 1998 and by other researchers in 1982 were used to examine historical trends in trace-element concentration and to determine anthropogenic sources of contaminants. Cores collected in 1982 from Mirror Lake, a high-mountain reference location, showed an enrichment of arsenic, cadmium, copper, lead, tin, and zinc in the surface sediments relative to the deeper sediments, indicating that enrichment likely began after about 1900. This enrichment was attributed to atmospheric deposition during the period of metal-ore mining and smelting. A core from Echo Reservoir, in the Weber River Basin, however, showed a different pattern of trace-element concentration that was attributed to a local source. This site is located downstream from the Park City mining district, which is the most likely historical source of trace elements. Cores collected in 1998 from Farmington Bay show that the concentration of lead began to increase after 1842 and peaked during the mid-1980s and has been in decline since. Recent sediments deposited during 1996-98 indicate a 41- to 62-percent reduction since the peak in the mid-1980s.The concentration of trace elements in streambed sediment was greatest at sites that have been affected by historic mining, including sites on Little Cottonwood Creek in the Jordan River basin, Silver Creek in the Weber River basin, and the Weber River below the confluence with Silver Creek. There was significant correlation of lead concentrations in streambed sediment and fish tissue, but other trace elements did not correlate well. Streambed sediment and fish tissue collected from sites in the Bear River basin, which is predominantly rangeland and agriculture, generally had low concentrations of most elements.Sediment-quality guidelines were used to assess the relative toxicity of streambed-sediment sites to aquatic communities. Sites affected by mining exceeded the Probable Effect Concentration (PEC), the concentration at which it is likely there will be a negative effect on the aquatic community, for arsenic, cadmium, copper, lead, silver, mercury, and zinc. Sites that were not affected by mining did not exceed these criteria. Concentrations of trace elements in samples collected from the Great Salt Lake Basins study unit (GRSL) are high compared to those of samples collected nationally with the NAWQA program. Nine of 15 streambed-sediment samples and 11 of 14 fish-tissue samples had concentrations of at least one trace element greater than the concentration of 90 percent of the samples collected nationally during 1993-2000.Organic compounds that were examined in streambed sediment and fish-tissue samples also were examined in bed-sediment cores. A bed-sediment core from Farmington Bay of Great Salt Lake showed an increase in total polycyclic aromatic hydrocarbon (PAH) concentrations coincident with the increase in population in Salt Lake Valley, which drains into this bay. Analysis of streambed-sediment samples showed that the highest concentrations of PAHs were detected at urban sites, including two sites in the lower Jordan River (the Jordan River flows into Farmington Bay), the Weber River at Ogden Bay, and the Provo River near Provo. Other organic compounds detected in streambed sediment in the lower Jordan River were PCBs, DDT compounds, and chlordane compounds.Organic compounds were detected more frequently in fish tissue than in streambed sediment. Chlordane compounds and PCBs were detected more frequently at urban sites. DDT compounds were detected at 13 of 15 sites including urban and agricultural sites. Concentrations of total DDT in fish tissue exceeded the guideline for protection of fish-eating wildlife at two urban sites. The concentration of organic compounds in the GRSL study unit is low compared with that of samples collected nationally.

Contribution and distribution of inorganic ions and organic compounds to the osmotic adjustment in Halostachys caspica response to salt stress

PubMed Central

Zeng, Youling; Li, Ling; Yang, Ruirui; Yi, Xiaoya; Zhang, Baohong

2015-01-01

The mechanism by which plants cope with salt stress remains poorly understood. The goal of this study is to systematically investigate the contribution and distribution of inorganic ions and organic compounds to the osmotic adjustment (OA) in the halophyte species Halostachys caspica. The results indicate that 100–200 mM NaCl is optimal for plant growth; the water content and degree of succulence of the assimilating branches are higher in this treatment range than that in other treatments; parenchyma cells are more numerous with 100 mM NaCl treatment than they are in control. Inorganic ions (mainly Na+ and Cl-) may play a more important role than organic compounds in NaCl-induced OA and are the primary contributors in OA in H. caspica. The inorganic ions and organic solutes display a tissue-dependent distribution. Na+ and Cl− are accumulated in the reproductive organs and within assimilating branches, which may represent a mechanism for protecting plant growth by way of salt ion dilution and organ abscission. Additionally, OA via increased accumulation of organic substances also protected plant growth and development. This finding provides additional evidence for plant tolerance to salinity stress which can be used for breeding new cultivars for stress tolerance. PMID:26350977

Amino acid-substituted gemini surfactant-based nanoparticles as safe and versatile gene delivery agents.

PubMed

Singh, Jagbir; Yang, Peng; Michel, Deborah; Verrall, Ronald E; Foldvari, Marianna; Badea, Ildiko

2011-05-01

Gene based therapy represents an important advance in the treatment of diseases that heretofore have had either no treatment or cure. To capitalize on the true potential of gene therapy, there is a need to develop better delivery systems that can protect these therapeutic biomolecules and deliver them safely to the target sites. Recently, we have designed and developed a series of novel amino acid-substituted gemini surfactants with the general chemical formula C(12)H(25) (CH(3))(2)N(+)-(CH(2))(3)-N(AA)-(CH(2))(3)-N(+) (CH(3))(2)-C(12)H(25) (AA= glycine, lysine, glycyl-lysine and, lysyl-lysine). These compounds were synthesized and tested in rabbit epithelial cells using a model plasmid and a helper lipid. Plasmid/gemini/lipid (P/G/L) nanoparticles formulated using these novel compounds achieved higher gene expression than the nanoparticles containing the parent unsubstituted compound. In this study, we evaluated the cytotoxicity of P/G/L nanoparticles and explored the relationship between transfection efficiency/toxicity and their physicochemical characteristics (such as size, binding properties, etc.). An overall low toxicity is observed for all complexes with no significant difference among substituted and unsubstituted compounds. An interesting result revealed by the dye exclusion assay suggests a more balanced protection of the DNA by the glycine and glycyl-lysine substituted compounds. Thus, the higher transfection efficiency is attributed to the greater biocompatibility and flexibility of the amino acid/peptide-substituted gemini surfactants and demonstrates the feasibility of using amino acid-substituted gemini surfactants as gene carriers for the treatment of diseases affecting epithelial tissue.

Integrative Analyses of Nontargeted Volatile Profiling and Transcriptome Data Provide Molecular Insight into VOC Diversity in Cucumber Plants (Cucumis sativus)1[OPEN

PubMed Central

Wei, Guo; Tian, Peng; Zhang, Fengxia; Qin, Hao; Miao, Han; Chen, Qingwen; Hu, Zhongyi; Wang, Meijiao; Chen, Mingsheng

2016-01-01

Plant volatile organic compounds, which are generated in a tissue-specific manner, play important ecological roles in the interactions between plants and their environments, including the well-known functions of attracting pollinators and protecting plants from herbivores/fungi attacks. However, to date, there have not been reports of holistic volatile profiling of the various tissues of a single plant species, even for the model plant species. In this study, we qualitatively and quantitatively analyzed 85 volatile chemicals, including 36 volatile terpenes, in 23 different tissues of cucumber (Cucumis sativus) plants using solid-phase microextraction combined with gas chromatography-mass spectrometry. Most volatile chemicals were found to occur in a highly tissue-specific manner. The consensus transcriptomes for each of the 23 cucumber tissues were generated with RNA sequencing data and used in volatile organic compound-gene correlation analysis to screen for candidate genes likely to be involved in cucumber volatile biosynthetic pathways. In vitro biochemical characterization of the candidate enzymes demonstrated that TERPENE SYNTHASE11 (TPS11)/TPS14, TPS01, and TPS15 were responsible for volatile terpenoid production in the roots, flowers, and fruit tissues of cucumber plants, respectively. A functional heteromeric geranyl(geranyl) pyrophosphate synthase, composed of an inactive small subunit (type I) and an active large subunit, was demonstrated to play a key role in monoterpene production in cucumber. In addition to establishing a standard workflow for the elucidation of plant volatile biosynthetic pathways, the knowledge generated from this study lays a solid foundation for future investigations of both the physiological functions of cucumber volatiles and aspects of cucumber flavor improvement. PMID:27457123

Chemical Protection Against Radiation Damage

ERIC Educational Resources Information Center

Campaigne, Ernest

1969-01-01

Discusses potential war time and medical uses for chemical compounds giving protection against radiation damage. Describes compounds known to protect, research aimed at discovering such compounds, and problems of toxicity. (EB)

The effects of lycopene on DNA damage and oxidative stress on indomethacin-induced gastric ulcer in rats.

PubMed

Boyacioglu, Murat; Kum, Cavit; Sekkin, Selim; Yalinkilinc, Hande Sultan; Avci, Hamdi; Epikmen, Erkmen Tugrul; Karademir, Umit

2016-04-01

Lycopene, the main antioxidant compound present in tomatoes, has high singlet oxygen- and peroxyl radicals-quenching ability, resulting in protection against oxidative damage in aerobic cell. Indomethacin is a nonsteroidal anti-inflammatory drug, and can promote oxidative damage in gastric tissue. The aim of this study was to investigate the protective effects of lycopene on an indomethacin-induced gastric ulcer model. A total of 42 adult male Wistar rats were divided into six groups of seven animals as follows: control, indomethacin, lansoprazole, lycopene 10 mg/kg, lycopene 50 mg/kg and lycopene 100 mg/kg. Gastric ulcers were induced by oral administration of indomethacin, after which the differing doses of lycopene were administered by oral gavage. The efficacy of lycopene was compared with lansoprazole. DNA damage of lymphocytes was measured by comet assay. Activities of superoxide dismutase, catalase and myeloperoxidase, as well as malondialdehyde and glutathione levels were determined in stomach tissue. This tissue was also taken for pathological investigations. The TUNEL method was used to detect apoptotic cells in paraffin sections. The results showed that 100 mg/kg lycopene administration significantly decreased % Tail DNA and Mean Tail Moment in the gastric ulcer group, compared with the other treatment groups. This same dose of lycopene also significantly decreased high malondialdehyde level and myeloperoxidase activity, and increased the activity of antioxidant enzymes (with the exception of catalase) in tissue. Apoptosis rates in the stomachs of the rats correlated with the biochemical and histopathological findings. These results indicated that lycopene might have a protective effect against indomethacin-induced gastric ulcer and oxidative stress in rats. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Radioprotective Action of Low-Intensity Light into the Red Absorption Band of Endogenous Molecular Oxygen

NASA Astrophysics Data System (ADS)

Ivanov, A. V.; Mashalov, A. A.; Zakharov, S. D.

2016-08-01

Application of ionizing radiation in oncology (radiation therapy) is a widespread way to eliminate malignant tumors. Normal tissues are inevitable included in any radiation field, and their reliable protection is actual till now. All attempts to solve the problem are based on search of effective radioprotectors, i.e. chemical compounds of various classes, which should be entered into the patient. To date about 50,000 compounds with some radioprotection properties had been tested, but the most effective of them have been simultaneously the most toxic. Here the preliminary results of researches devoted to development of an optical technique on basis of the light-oxygen effect for the protection of women with breast cancer from side effects of the radiation therapy are presented. A low intensity emission of the semiconductor laser in a red spectral interval was used to excite a very small quantity of endogenous molecular oxygen in O2(1Δg) state. It is shown, that application of the method at occurrence of earliest signs of radiation injury allows notably reducing dangerous breaks in radiation therapy course.

Antimicrobial Protection of Marsupial Pouch Young

PubMed Central

Cheng, Yuanyuan; Belov, Katherine

2017-01-01

Marsupials diverged from eutherian mammals about 148 million years ago and represent a unique lineage of mammals with distinctive morphological and reproductive characteristics. Marsupials have significantly shorter gestation periods than eutherians. Pregnancy typically ranges from 15 to 35 days, with young being born at a very early developmental stage and lacking differentiated lymphoid tissues and mature effector cells. Recent microbiome studies of the marsupial pouch revealed that marsupial young can face intense microbial challenges after birth, as the pouch contains a broad range of Gram-positive and Gram-negative bacteria. Antimicrobials are believed to play a significant role in the immune protection of marsupial newborns during their pouch life. The skin of the post-reproductive pouch secretes antimicrobial lysozyme and dermcidin, which may contribute to the decreased density of certain bacteria in the pouch. A range of antimicrobial agents, such as immunoglobulins, lysozyme, transferrin, and cathelicidins, have been identified in marsupial milk. Antimicrobial assays have revealed that marsupial cathelicidins have broad-spectrum activity against a variety of bacteria and fungi, including several multi-drug resistant strains. In this article, we will review the action mechanisms of these antimicrobial compounds and discuss how they protect marsupial newborns from potentially pathogenic bacteria inside the pouch. We will also discuss the potential of marsupial antimicrobial compounds as a source of novel antibiotics. PMID:28326070

Assessment of the potential activity of major dietary compounds as selective estrogen receptor modulators in two distinct cell models for proliferation and differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lecomte, Sylvain; Lelong, Marie; Bourgine, Gaëlle

Estrogen receptors (ERs) α and β are distributed in most tissues of women and men. ERs are bound by estradiol (E2), a natural hormone, and mediate the pleiotropic and tissue-specific effects of E2, such as proliferation of breast epithelial cells or protection and differentiation of neuronal cells. Numerous environmental molecules, called endocrine disrupting compounds, also interact with ERs. Phytoestrogens belong to this large family and are considered potent therapeutic molecules that act through their selective estrogen receptor modulator (SERM) activity. Using breast cancer cell lines as a model of estrogen-dependent proliferation and a stably ER-expressing PC12 cell line as amore » model of neuronal differentiating cells, we studied the SERM activity of major dietary compounds, such as apigenin, liquiritigenin, daidzein, genistein, coumestrol, resveratrol and zearalenone. The ability of these compounds to induce ER-transactivation and breast cancer cell proliferation and enhance Nerve Growth Factor (NGF) -induced neuritogenesis was assessed. Surprisingly, although all compounds were able to activate the ER through an estrogen responsive element reporter gene, they showed differential activity toward proliferation or differentiation. Apigenin and resveratrol showed a partial or no proliferative effect on breast cancer cells but fully contributed to the neuritogenesis effect of NGF. However, daidzein and zearalenone showed full effects on cellular proliferation but did not induce cellular differentiation. In summary, our results suggest that the therapeutic potential of phytoestrogens can diverge depending on the molecule and the phenotype considered. Hence, apigenin and resveratrol might be used in the development of therapeutics for breast cancer and brain diseases. - Highlights: • SERM activity of dietary compounds on proliferation and differentiation is studied. • All the dietary compounds tested transactivate estrogen receptors. • Apigenin and resveratrol could be good candidates for future therapeutics. • Daidzein and zearalenone are to be avoided to maintain human health.« less

Demonstration of carboxylesterase in cytology samples of human nasal respiratory epithelium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodgers, D.A.; Nikula, K.J.; Avila, K.

1995-12-01

The epithelial lining of the nasal airways is a target for responses induced by a variety of toxicant exposures. The high metabolic capacity of this tissue has been suggested to play a role in both protection of the airways through detoxication of certain toxicants, as well as in activation of other compounds to more toxic metabolites. Specifically, nasal carboxylesterase (CE) has been shown to mediate the toxicity of inhaled esters and acrylates by converting them to more toxic acid and alcohol metabolites which can be cytotoxic and/or carcinogenic to the nasal mucosa. Due to difficulties in extrapolating rodent models tomore » human, new paradigms using human cells and tissues are essential to understanding and evaluating the metabolic processes in human nasal epithelium.« less

21 CFR 500.82 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... the sponsored compound in the target tissue of the target animal. R m means the concentration of the... means any compound present in edible tissues of the target animal which results from the use of the... use. Target tissue means the edible tissue selected to monitor for residues in the target animals...

21 CFR 500.82 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... the sponsored compound in the target tissue of the target animal. R m means the concentration of the... means any compound present in edible tissues of the target animal which results from the use of the... use. Target tissue means the edible tissue selected to monitor for residues in the target animals...

[Soya isoflavones and evidences on cardiovascular protection].

PubMed

González Cañete, Natalia; Durán Agüero, Samuel

2014-06-01

Soya isoflavones represent a group of non-nutritive, bioactive compounds, of non-steroidal phenolic nature that are present in soy bean and derived foods. They share with other compounds the capacity of binding to estrogenic receptors from different cells and tissues so that they may act as phytoestrogens. The current interest in these compounds comes from the knowledge that in Asian populations with high levels of their consumption the prevalence of cancer and cardiovascular disease is lower, as compared to the Western countries populations. This cardiovascular benefit would be the result not only of the modulation of plasma lipids, which is a widely studied mechanism. This paper reviews the published evidence about the beneficial effects of soya isoflavones and the different mechanisms of action that would benefit cardiovascular health and that surpass the mechanisms traditionally approached such as the modulation of plasma lipids, and that implicate the regulation of cellular and enzymatic functions in situations such as inflammation, thrombosis, and atherosclerotic progression. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

CLOSED-LOOP STRIPPING ANALYSIS (CLSA) OF ...

EPA Pesticide Factsheets

Synthetic musk compounds are used as inexpensive fragrance materials for the production of perfumes and as additives to soap, detergent, and shampoo. They have been found in surface water, fish tissues, and human breast milk. The ubiquity of this class of compounds in the environment is attributable to high use and release into the environment. Current techniques for separating these compounds from fish tissues require tedious sample clean-up procedures. To obtain fat-free extracts, gel permeation chromatography (GPC), column chromatography using alumina, and silica gel, and thin layer chromatography (TLC clean-up procedures are frequently employed. Despite the considerable effort and resources devoted to these processes, a fraction of the lipids and lipid-like compounds frequently remains in the extracts. These low-level lipids foul injection liners, contaminate columns, and yield elevated baselines during gas chromatographic analysis of synthetic musk compounds. In this study, a simple method for the determination of synthetic musk compounds in fish tissues has been developed. Closed-loop stripping of saponified fish tissues in a I -L Wheaton purge- and-trap vessel, is used to strip compounds with high vapor pressures such as synthetic musks from the matrix onto a solid sorbent (Abselut Nexus). This technique is useful for screening biological tissues that contain lipids for musk compounds. Analytes are desorbed from the sorbent trap sequentially with polar an

Screen of FDA-approved drug library reveals compounds that protect hair cells from aminoglycosides and cisplatin

PubMed Central

Vlasits, Anna L.; Simon, Julian A.; Raible, David W.; Rubel, Edwin W; Owens, Kelly N.

2012-01-01

Loss of mechanosensory hair cells in the inner ear accounts for many hearing loss and balance disorders. Several beneficial pharmaceutical drugs cause hair cell death as a side effect. These include aminoglycoside antibiotics, such as neomycin, kanamycin and gentamicin, and several cancer chemotherapy drugs, such as cisplatin. Discovering new compounds that protect mammalian hair cells from toxic insults is experimentally difficult because of the inaccessibility of the inner ear. We used the zebrafish lateral line sensory system as an in vivo screening platform to survey a library of FDA-approved pharmaceuticals for compounds that protect hair cells from neomycin, gentamicin, kanamycin and cisplatin. Ten compounds were identified that provide protection from at least two of the four toxins. The resulting compounds fall into several drug classes, including serotonin and dopamine-modulating drugs, adrenergic receptor ligands, and estrogen receptor modulators. The protective compounds show different effects against the different toxins, supporting the idea that each toxin causes hair cell death by distinct, but partially overlapping, mechanisms. Furthermore, some compounds from the same drug classes had different protective properties, suggesting that they might not prevent hair cell death by their known target mechanisms. Some protective compounds blocked gentamicin uptake into hair cells, suggesting that they may block mechanotransduction or other routes of entry. The protective compounds identified in our screen will provide a starting point for studies in mammals as well as further research discovering the cellular signaling pathways that trigger hair cell death. PMID:22967486

Microgravity Stress: Bone and Connective Tissue.

PubMed

Bloomfield, Susan A; Martinez, Daniel A; Boudreaux, Ramon D; Mantri, Anita V

2016-03-15

The major alterations in bone and the dense connective tissues in humans and animals exposed to microgravity illustrate the dependency of these tissues' function on normal gravitational loading. Whether these alterations depend solely on the reduced mechanical loading of zero g or are compounded by fluid shifts, altered tissue blood flow, radiation exposure, and altered nutritional status is not yet well defined. Changes in the dense connective tissues and intervertebral disks are generally smaller in magnitude but occur more rapidly than those in mineralized bone with transitions to 0 g and during recovery once back to the loading provided by 1 g conditions. However, joint injuries are projected to occur much more often than the more catastrophic bone fracture during exploration class missions, so protecting the integrity of both tissues is important. This review focuses on the research performed over the last 20 years in humans and animals exposed to actual spaceflight, as well as on knowledge gained from pertinent ground-based models such as bed rest in humans and hindlimb unloading in rodents. Significant progress has been made in our understanding of the mechanisms for alterations in bone and connective tissues with exposure to microgravity, but intriguing questions remain to be solved, particularly with reference to biomedical risks associated with prolonged exploration missions. Copyright © 2016 John Wiley & Sons, Inc.

Engineered human broncho-epithelial tissue-like assemblies

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J. (Inventor)

2012-01-01

Three-dimensional human broncho-epithelial tissue-like assemblies (TLAs) are produced in a rotating wall vessel (RWV) with microcarriers by coculturing mesenchymal bronchial-tracheal cells (BTC) and bronchial epithelium cells (BEC). These TLAs display structural characteristics and express markers of in vivo respiratory epithelia. TLAs are useful for screening compounds active in lung tissues such as antiviral compounds, cystic fibrosis treatments, allergens, and cytotoxic compounds.

Adaptive model-predictive controller for magnetic resonance guided focused ultrasound therapy.

PubMed

de Bever, Joshua; Todd, Nick; Payne, Allison; Christensen, Douglas A; Roemer, Robert B

2014-11-01

Minimising treatment time and protecting healthy tissues are conflicting goals that play major roles in making magnetic resonance image-guided focused ultrasound (MRgFUS) therapies clinically practical. We have developed and tested in vivo an adaptive model-predictive controller (AMPC) that reduces treatment time, ensures safety and efficacy, and provides flexibility in treatment set-up. The controller realises time savings by modelling the heated treatment cell's future temperatures and thermal dose accumulation in order to anticipate the optimal time to switch to the next cell. Selected tissues are safeguarded by a configurable temperature constraint. Simulations quantified the time savings realised by each controller feature as well as the trade-offs between competing safety and treatment time parameters. In vivo experiments in rabbit thighs established the controller's effectiveness and reliability. In all in vivo experiments the target thermal dose of at least 240 CEM43 was delivered everywhere in the treatment volume. The controller's temperature safety limit reliably activated and constrained all protected tissues to <9 CEM43. Simulations demonstrated the path independence of the controller, and that a path which successively proceeds to the hottest untreated neighbouring cell leads to significant time savings, e.g. when compared to a concentric spiral path. Use of the AMPC produced a compounding time-saving effect; reducing the treatment cells' heating times concurrently reduced heating of normal tissues, which eliminated cooling periods. Adaptive model-predictive control can automatically deliver safe, effective MRgFUS treatments while significantly reducing treatment times.

Compound edaravone alleviates lipopolysaccharide (LPS)-induced acute lung injury in mice.

PubMed

Zhang, Zhengping; Luo, Zhaowen; Bi, Aijing; Yang, Weidong; An, Wenji; Dong, Xiaoliang; Chen, Rong; Yang, Shibao; Tang, Huifang; Han, Xiaodong; Luo, Lan

2017-09-15

Acute lung injury (ALI) represents an unmet medical need with an urgency to develop effective pharmacotherapies. Compound edaravone, a combination of edaravone and borneol, has been developed for treatment of ischemia stroke in clinical phase III study. The purpose of the present study is to investigate the anti-inflammatory effect of compound edaravone on lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 cells and the therapeutic efficacy on LPS-induced ALI in mice. Edaravone and compound edaravone concentration-dependently decreased LPS-induced interleukin-6 (IL-6) production and cyclooxygenase-2 (COX-2) expression in RAW264.7 cells. The efficiency of compound edaravone was stronger than edaravone alone. In the animal study, compound edaravone was injected intravenously to mice after intratracheal instillation of LPS. It remarkably alleviated LPS-induced lung injury including pulmonary histological abnormalities, polymorphonuclear leukocyte (PMN) infiltration and extravasation. Further study demonstrated that compound edaravone suppressed LPS-induced TNF-α and IL-6 increase in mouse serum and bronchoalveolar lavage (BAL) fluid, and inhibited LPS-induced nuclear factor-κB (NF-κB) activation and COX-2 expression in mice lung tissues. Importantly, our findings demonstrated that the compound edaravone showed a stronger protective effect against mouse ALI than edaravone alone, which suggested the synergies between edaravone and borneol. In conclusion, compound edaravone could be a potential novel therapeutic drug for ALI treatment and borneol might produce a synergism with edaravone. Copyright © 2017 Elsevier B.V. All rights reserved.

One-Compound-Multi-Target: Combination Prospect of Natural Compounds with Thrombolytic Therapy in Acute Ischemic Stroke

PubMed Central

Chen, Han-Sen; Qi, Su-Hua; Shen, Jian-Gang

2017-01-01

Abstract: Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PA's therapeutic time window. However, therapies modulating single target seem not to be satisfied, and a multi-target strategy is warranted to resolve such complex disease. Recently, large amount of efforts have been made to explore the active compounds from herbal supplements to treat ischemic stroke. Some natural compounds revealed both neuro- and blood-brain-barrier (BBB)-protective effects by concurrently targeting multiple cellular signaling pathways in cerebral ischemia-reperfusion injury. Thus, those compounds are potential to be one-drug-multi-target agents as combined therapy with t-PA for ischemic stroke. In this review article, we summarize current progress about molecular targets involving in t-PA-mediated HT and neurotoxicity in ischemic brain injury. Based on these targets, we select 23 promising compounds from currently available literature with the bioactivities simultaneously targeting several important molecular targets. We propose that those compounds merit further investigation as combined therapy with t-PA. Finally, we discuss the potential drawbacks of the natural compounds' studies and raise several important issues to be addressed in the future for the development of natural compound as an adjunct therapy. PMID:27334020

Hydroxytyrosol prevents diet-induced metabolic syndrome and attenuates mitochondrial abnormalities in obese mice.

PubMed

Cao, Ke; Xu, Jie; Zou, Xuan; Li, Yuan; Chen, Cong; Zheng, Adi; Li, Hao; Li, Hua; Szeto, Ignatius Man-Yau; Shi, Yujie; Long, Jiangang; Liu, Jiankang; Feng, Zhihui

2014-02-01

A Mediterranean diet rich in olive oil has profound influence on health outcomes including metabolic syndrome. However, the active compound and detailed mechanisms still remain unclear. Hydroxytyrosol (HT), a major polyphenolic compound in virgin olive oil, has received increased attention for its antioxidative activity and regulation of mitochondrial function. Here, we investigated whether HT is the active compound in olive oil exerting a protective effect against metabolic syndrome. In this study, we show that HT could prevent high-fat-diet (HFD)-induced obesity, hyperglycemia, hyperlipidemia, and insulin resistance in C57BL/6J mice after 17 weeks supplementation. Within liver and skeletal muscle tissues, HT could decrease HFD-induced lipid deposits through inhibition of the SREBP-1c/FAS pathway, ameliorate HFD-induced oxidative stress by enhancing antioxidant enzyme activities, normalize expression of mitochondrial complex subunits and mitochondrial fission marker Drp1, and eventually inhibit apoptosis activation. Moreover, in muscle tissue, the levels of mitochondrial carbonyl protein were decreased and mitochondrial complex activities were significantly improved by HT supplementation. In db/db mice, HT significantly decreased fasting glucose, similar to metformin. Notably, HT decreased serum lipid, at which metformin failed. Also, HT was more effective at decreasing the oxidation levels of lipids and proteins in both liver and muscle tissue. Similar to the results in the HFD model, HT decreased muscle mitochondrial carbonyl protein levels and improved mitochondrial complex activities in db/db mice. Our study links the olive oil component HT to diabetes and metabolic disease through changes that are not limited to decreases in oxidative stress, suggesting a potential pharmaceutical or clinical use of HT in metabolic syndrome treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

Methionine and Choline Supply during the Periparturient Period Alter Plasma Amino Acid and One-Carbon Metabolism Profiles to Various Extents: Potential Role in Hepatic Metabolism and Antioxidant Status.

PubMed

Zhou, Zheng; Vailati-Riboni, Mario; Luchini, Daniel N; Loor, Juan J

2016-12-29

The objective of this study was to profile plasma amino acids (AA) and derivatives of their metabolism during the periparturient period in response to supplemental rumen-protected methionine (MET) or rumen-protected choline (CHOL). Forty cows were fed from -21 through 30 days around parturition in a 2 × 2 factorial design a diet containing MET or CHOL. MET supply led to greater circulating methionine and proportion of methionine in the essential AA pool, total AA, and total sulfur-containing compounds. Lysine in total AA also was greater in these cows, indicating a better overall AA profile. Sulfur-containing compounds (cystathionine, cystine, homocystine, and taurine) were greater in MET-fed cows, indicating an enriched sulfur-containing compound pool due to enhanced transsulfuration activity. Circulating essential AA and total AA concentrations were greater in cows supplied MET due to greater lysine, arginine, tryptophan, threonine, proline, asparagine, alanine, and citrulline. In contrast, CHOL supply had no effect on essential AA or total AA, and only tryptophan and cystine were greater. Plasma 3-methylhistidine concentration was lower in response to CHOL supply, suggesting less tissue protein mobilization in these cows. Overall, the data revealed that enhanced periparturient supply of MET has positive effects on plasma AA profiles and overall antioxidant status.

Methionine and Choline Supply during the Periparturient Period Alter Plasma Amino Acid and One-Carbon Metabolism Profiles to Various Extents: Potential Role in Hepatic Metabolism and Antioxidant Status

PubMed Central

Zhou, Zheng; Vailati-Riboni, Mario; Luchini, Daniel N.; Loor, Juan J.

2016-01-01

The objective of this study was to profile plasma amino acids (AA) and derivatives of their metabolism during the periparturient period in response to supplemental rumen-protected methionine (MET) or rumen-protected choline (CHOL). Forty cows were fed from −21 through 30 days around parturition in a 2 × 2 factorial design a diet containing MET or CHOL. MET supply led to greater circulating methionine and proportion of methionine in the essential AA pool, total AA, and total sulfur-containing compounds. Lysine in total AA also was greater in these cows, indicating a better overall AA profile. Sulfur-containing compounds (cystathionine, cystine, homocystine, and taurine) were greater in MET-fed cows, indicating an enriched sulfur-containing compound pool due to enhanced transsulfuration activity. Circulating essential AA and total AA concentrations were greater in cows supplied MET due to greater lysine, arginine, tryptophan, threonine, proline, asparagine, alanine, and citrulline. In contrast, CHOL supply had no effect on essential AA or total AA, and only tryptophan and cystine were greater. Plasma 3-methylhistidine concentration was lower in response to CHOL supply, suggesting less tissue protein mobilization in these cows. Overall, the data revealed that enhanced periparturient supply of MET has positive effects on plasma AA profiles and overall antioxidant status. PMID:28036059

Resistance mechanisms and their difference between the root and leaf of Microsorum pteropus - A novel potential aquatic cadmium hyperaccumulator.

PubMed

Lan, Xin-Yu; Yang, Bin; Yan, Yun-Yun; Li, Xin-Yuan; Xu, Fu-Liu

2018-03-01

Microsorum pteropus (M. pteropus), an aquatic Polypodiaceae fern, was identified as a novel potential cadmium (Cd) hyperaccumulator in our previous study. This study reveals the Cd-resistance mechanisms and their difference between the root and leaf of M. pteropus based on analyses of photosynthesis, antioxidant systems and gene expression. A high level of Cd at 500μM was used to treat the samples to test the effects of this compound. Superoxide dismutase (SOD), peroxidase (POD), malondialdehyde (MDA) and flavonoids were used as indicators for antioxidant system changes. Five chlorophyll fluorescent parameters including the maximal photochemical efficiency of photosystem II (F v /F m ), effective quantum yield of photosystem II (Y(II)), photochemical quenching (qP), nonphotochemical quenching (qN) and electron transport rate (ETR) were measured to determine the photosynthetic changes. RNA-sequencing analysis was used to study the changes in gene expression. The results showed that after exposure to high levels of Cd, the concentrations of enzymatic oxidants (SOD and POD) were significantly increased, while the MDA levels were significantly decreased. There were no significant changes for the chlorophyll fluorescent parameters during Cd stress, which indicates that M. pteropus is highly effective at protecting itself. Certain functional genes, including photosystem genes and secondary metabolites, had significantly altered levels of expression. Different Cd-resistance mechanisms were found between the root and leaf tissues of M. pteropus. The root tissues of M. pteropus resist Cd damage using antioxidants, while its leaf tissues mainly protect themselves using photosystem self-protection. Copyright © 2017 Elsevier B.V. All rights reserved.

Abcb4 acts as multixenobiotic transporter and active barrier against chemical uptake in zebrafish (Danio rerio) embryos

PubMed Central

2013-01-01

Background In mammals, ABCB1 constitutes a cellular “first line of defense” against a wide array of chemicals and drugs conferring cellular multidrug or multixenobiotic resistance (MDR/MXR). We tested the hypothesis that an ABCB1 ortholog serves as protection for the sensitive developmental processes in zebrafish embryos against adverse compounds dissolved in the water. Results Indication for ABCB1-type efflux counteracting the accumulation of chemicals in zebrafish embryos comes from experiments with fluorescent and toxic transporter substrates and inhibitors. With inhibitors present, levels of fluorescent dyes in embryo tissue and sensitivity of embryos to toxic substrates were generally elevated. We verified two predicted sequences from zebrafish, previously annotated as abcb1, by cloning; our synteny analyses, however, identified them as abcb4 and abcb5, respectively. The abcb1 gene is absent in the zebrafish genome and we explored whether instead Abcb4 and/or Abcb5 show toxicant defense properties. Quantitative real-time polymerase chain reaction (qPCR) analyses showed the presence of transcripts of both genes throughout the first 48 hours of zebrafish development. Similar to transporter inhibitors, morpholino knock-down of Abcb4 increased accumulation of fluorescent substrates in embryo tissue and sensitivity of embryos toward toxic compounds. In contrast, morpholino knock-down of Abcb5 did not exert this effect. ATPase assays with recombinant protein obtained with the baculovirus expression system confirmed that dye and toxic compounds act as substrates of zebrafish Abcb4 and inhibitors block its function. The compounds tested comprised model substrates of human ABCB1, namely the fluorescent dyes rhodamine B and calcein-am and the toxic compounds vinblastine, vincristine and doxorubicin; cyclosporin A, PSC833, MK571 and verapamil were applied as inhibitors. Additionally, tests were performed with ecotoxicologically relevant compounds: phenanthrene (a polycyclic aromatic hydrocarbon) and galaxolide and tonalide (two polycyclic musks). Conclusions We show that zebrafish Abcb4 is a cellular toxicant transporter and provides protection of embryos against toxic chemicals dissolved in the water. Zebrafish Abcb4 thus is functionally similar to mammalian ABCB1, but differs from mammalian ABCB4, which is not involved in cellular resistance to chemicals but specifically transports phospholipids in the liver. Our data have important implications: Abcb4 could affect bioavailability - and thus toxicologic and pharmacologic potency - of chemicals to zebrafish embryos and inhibition of Abcb4 therefore causes chemosensitization, that is, enhanced sensitivity of embryos to toxicants. These aspects should be considered in (eco)toxicologic and pharmacologic chemical screens with the zebrafish embryo, a major vertebrate model. PMID:23773777

Surgical Management of Compound Odontoma Associated with Unerupted Tooth

PubMed Central

Marini, Roberta; Pacifici, Luciano

2015-01-01

Odontomas represent the most common type of odontogenic benign jaws tumors among patients younger than 20 years of age. These tumors are composed of enamel, dentine, cementum, and pulp tissue. According to the World Health Organization classification, two distinct types of odontomas are acknowledged: complex and compound odontoma. In complex odontomas, all dental tissues are formed, but appeared without an organized structure. In compound odontomas, all dental tissues are arranged in numerous tooth-like structures known as denticles. Compound odontomas are often associated with impacted adjacent permanent teeth and their surgical removal represents the best therapeutic option. A case of a 20-year-old male patient with a compound odontoma-associated of impacted maxillary canine is presented. A minimally invasive surgical technique is adopted to remove the least amount of bone tissue as far as possible. PMID:26199762

CLOSED-LOOP STRIPPING ANALYSIS (CLSA) OF ...

EPA Pesticide Factsheets

Synthetic musk compounds have been found in surface water, fish tissues, and human breast milk. Current techniques for separating these compounds from fish tissues require tedious sample clean-upprocedures A simple method for the deterrnination of these compounds in fish tissues has been developed. Closed-loop stripping of saponified fish tissues in a I -L Wheaton purge-and-trap vessel is used to strip compounds with high vapor pressures such as synthetic musks from the matrix onto a solid sorbent (Abselut Nexus). This technique is useful for screening biological tissues that contain lipids for musk compounds. Analytes are desorbed from the sorbent trap sequentially with polar and nonpolar solvents, concentrated, and directly analyzed by high resolution gas chromatography coupled to a mass spectrometer operating in the selected ion monitoring mode. In this paper, we analyzed two homogenized samples of whole fish tissues with spiked synthetic musk compounds using closed-loop stripping analysis (CLSA) and pressurized liquid extraction (PLE). The analytes were not recovered quantitatively but the extraction yield was sufficiently reproducible for at least semi-quantitative purposes (screening). The method was less expensive to implement and required significantly less sample preparation than the PLE technique. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water,

The Prospective Role of Plant Products in Radiotherapy of Cancer: A Current Overview

PubMed Central

Hazra, Banasri; Ghosh, Subhalakshmi; Kumar, Amit; Pandey, B. N.

2012-01-01

Treatment of cancer often requires exposure to radiation, which has several limitations involving non-specific toxicity toward normal cells, reducing the efficacy of treatment. Efforts are going on to find chemical compounds which would effectively offer protection to the normal tissues after radiation exposure during radiotherapy of cancer. In this regard, plant-derived compounds might serve as “leads” to design ideal radioprotectors/radiosensitizers. This article reviews some of the recent findings on prospective medicinal plants, phytochemicals, and their analogs, based on both in vitro and in vivo tumor models especially focused with relevance to cancer radiotherapy. Also, pertinent discussion has been presented on the molecular mechanism of apoptotic death in relation to the oxidative stress in cancer cells induced by some of these plant samples and their active constituents. PMID:22291649

Rapamycin ameliorates brain metabolites alterations after transient focal ischemia in rats.

PubMed

Chauhan, Anjali; Sharma, Uma; Jagannathan, Naranamangalam R; Gupta, Yogendra Kumar

2015-06-15

Rapamycin has been shown to protect against middle cerebral artery occlusion (MCAo) induced ischemic injury. In this study, the neuroprotective effect of rapamycin on the metabolic changes induced by MCAo was evaluated using nuclear magnetic resonance (NMR) spectroscopy of brain tissues. MCAo in rats was induced by insertion of nylon filament. One hour after ischemia, rapamycin (250 µg/kg, i.p.) in dimethyl sulfoxide was administered. Reperfusion was done 2h after ischemia. Twenty-four hours after ischemia phospholipase A2 (PLA2) levels and metabolic changes were assessed. Perchloric acid extraction was performed on the brain of all animals (n=7; sham, vehicle; DMSO and rapamycin 250 µg/kg) and the various brain metabolites were assessed by NMR spectroscopy. In all 44 metabolites were assigned in the proton NMR spectrum of rat brain tissues. In the vehicle group, we observed increased lactate levels and decreased levels of glutamate/glutamine, choline containing compounds, creatine/phosphocreatine (Cr/PCr), taurine, myo-inositol, γ-amino butryic acid (GABA), N-aspartyl aspartate (NAA), purine and pyrimidine metabolites. In rapamycin treated rats, there was increase in the levels of choline containing compounds, NAA, myo-inositol, glutamate/glutamine, GABA, Cr/PCr and taurine as compared to those of vehicle control (P<0.05). Rapamycin treatment reduced PLA2 levels as compared to vehicle group (P<0.05). Our findings indicated that rapamycin reduced the increased PLA2 levels and altered brain metabolites after MCAo. These protective effects might be attributed to its effect on cell membrane metabolism; glutamate induced toxicity and calcium homeostasis in stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of pomegranate (Punica granatum L.) juice on kidney, liver, heart and testis histopathological changes, and the tissues lipid peroxidation and antioxidant status in lead acetate-treated rats.

PubMed

Aksu, D S; Sağlam, Y S; Yildirim, S; Aksu, T

2017-10-31

Pomegranate juice (PJ) contains relevant amounts of active biological compounds which alleviate the detrimental effects of chronic heavy metal exposure. This study investigated the protective potential of PJ against lead-induced oxidative stress. A total of forty adult male Sprague Dawley rats were divided into four experimental groups. The animals were fed a standard pellet diet and tap water ad libitum. The rats were divided into four groups (n=10 for each group): control, lead asetat (2000 ppm), low-treated PJ- a daily dose of 2.000 ppm lead plus 30µl pomegranate juice (included 1.050 µmol total polyphenols, gallic acid equivalent), and high-treated PJ- a daily dose of 2.000 ppm lead plus 60µl pomegranate juice (included 2.100 µmol total polyphenols, gallic acid equivalent). The treatments were delivered for 5 weeks. After the treatment period, the tissues samples (kidney, liver, heart and testis) were collected. Tissue lead (Pb) and mineral amounts (copper, zinc, and iron), tissues lipid peroxidation level and antioxidant status, and tissues histopathological changes were determined. The results showed that the highest rate lead loading was in the kidney and the testis. Pomegranate juice was decreased the lead levels of soft tissues examined; increased Zn amounts in tissues of which the lead accumulation was higher (kidney and the testis); decreased the copper, zinc and the iron levels of the liver and heart tissues, without creating a weakness in antioxidant capacity of these tissues, restricted the oxidative stress by decreasing lipid peroxidation, improved both of the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalaz (CAT), and the level of glutathione (GSH) in all the tissues examined in lead-treated groups. As histopathological findings, the cellular damage induced by lead in the tissues of the kidney, liver and the heart were observed to have been partially prevented by PJ treatment. The protective effect of PJ was more pronounced in the testis compared to those others.

Sea Buckthorn Leaf Extract Protects Jejunum and Bone Marrow of (60)Cobalt-Gamma-Irradiated Mice by Regulating Apoptosis and Tissue Regeneration.

PubMed

Bala, Madhu; Gupta, Manish; Saini, Manu; Abdin, M Z; Prasad, Jagdish

2015-01-01

A single dose (30 mg/kg body weight) of standardized sea buckthorn leaf extract (SBL-1), administered 30 min before whole body (60)Co-gamma-irradiation (lethal dose, 10 Gy), protected >90% of mice population. The purpose of this study was to investigate the mechanism of action of SBL-1 on jejunum and bone marrow, quantify key bioactive compounds, and analyze chemical composition of SBL-1. Study with 9-week-old inbred male Swiss albino Strain 'A' mice demonstrated that SBL-1 treatment before (60)Co-gamma-irradiation (10 Gy) significantly (p < 0.05) countered radiation induced decreases in jejunum crypts (1.27-fold), villi number (1.41-fold), villus height (1.25-fold), villus cellularity (2.27-fold), cryptal Paneth cells (1.89-fold), and Bcl2 level (1.54-fold). It countered radiation induced increases in cryptal apoptotic cells (1.64-fold) and Bax levels (1.88-fold). It also countered radiation (2 Gy and 3 Gy) induced bone marrow apoptosis (1.59-fold and 1.85-fold) and micronuclei frequency (1.72-fold and 2.6-fold). SBL-1 rendered radiation protection by promoting cryptal stem cells proliferation, by regulating apoptosis, and by countering radiation induced chromosomal damage. Quercetin, Ellagic acid, Gallic acid, high contents polyphenols, tannins, and thiols detected in SBL-1 may have contributed to radiation protection by neutralization of radiation induced oxidative species, supporting stem cell proliferation and tissue regeneration.

In vitro plant tissue culture: means for production of biological active compounds.

PubMed

Espinosa-Leal, Claudia A; Puente-Garza, César A; García-Lara, Silverio

2018-05-07

Plant tissue culture as an important tool for the continuous production of active compounds including secondary metabolites and engineered molecules. Novel methods (gene editing, abiotic stress) can improve the technique. Humans have a long history of reliance on plants for a supply of food, shelter and, most importantly, medicine. Current-day pharmaceuticals are typically based on plant-derived metabolites, with new products being discovered constantly. Nevertheless, the consistent and uniform supply of plant pharmaceuticals has often been compromised. One alternative for the production of important plant active compounds is in vitro plant tissue culture, as it assures independence from geographical conditions by eliminating the need to rely on wild plants. Plant transformation also allows the further use of plants for the production of engineered compounds, such as vaccines and multiple pharmaceuticals. This review summarizes the important bioactive compounds currently produced by plant tissue culture and the fundamental methods and plants employed for their production.

Probing cytotoxicity of nanoparticles and organic compounds using scanning proton microscopy, scanning electron microscopy and fluorescence microscopy

NASA Astrophysics Data System (ADS)

Tong, Yongpeng; Li, Changming; Liang, Feng; Chen, Jianmin; Zhang, Hong; Liu, Guoqing; Sun, Huibin; Luong, John H. T.

2008-12-01

Scanning proton microscopy, scanning electron microscopy (SEM) and fluorescence microscopy have been used to probe the cytotoxicity effect of benzo[a]pyrene (BaP), ethidium bromide (EB) and nanoparticles (ZnO, Al 2O 3 and TiO 2) on a T lymphoblastic leukemia Jurkat cell line. The increased calcium ion (from CaCl 2) in the culture medium stimulated the accumulation of BaP and EB inside the cell, leading to cell death. ZnO, Al 2O 3 and TiO 2 nanoparticles, however, showed a protective effect against these two organic compounds. Such inorganic nanoparticles complexed with BaP or EB which became less toxic to the cell. Fe 2O 3 nanoparticles as an insoluble particle model scavenged by macrophage were investigated in rats. They were scavenged out of the lung tissue about 48 h after infection. This result suggest that some insoluble inorganic nanoparticles of PM (particulate matters) showed protective effects on organic toxins induced acute toxic effects as they can be scavenged by macrophage cells. Whereas, some inorganic ions such as calcium ion in PM may help environmental organic toxins to penetrate cell membrane and induce higher toxic effect.

Essential tactics of tissue preparation and matrix nano-spotting for successful compound imaging mass spectrometry.

PubMed

Végvári, Akos; Fehniger, Thomas E; Gustavsson, Lena; Nilsson, Anna; Andrén, Per E; Kenne, Kerstin; Nilsson, Johan; Laurell, Thomas; Marko-Varga, György

2010-04-18

The ultimate goal of MALDI-Imaging Mass Spectrometry (MALDI-IMS) is to achieve spatial localization of analytes in tissue sections down to individual tissue compartments or even at the level of a few cells. With compound tissue imaging, it is possible to track the transportation of an unlabelled, inhaled reference compound within lung tissue, through the application of MALDI-IMS. The procedure for isolation and preparation of lung tissues is found to be crucial in order to preserve the anatomy and structure of the pulmonary compartments. To avoid delocalization of analytes within lung tissue compartments we have applied an in-house designed nano-spotter, based on a microdispenser mounted on an XY table, of which movement and spotting functionality were fully computer controlled. We demonstrate the usefulness of this platform in lung tissue sections isolated from rodent in vivo model, applied to compound tissue imaging as exemplified with the determination of the spatial distribution of (1alpha,2beta,4beta,7beta)-7-[(hydroxidi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.0(2,4)]nonane, also known as tiotropium. We provide details on tissue preparation protocols and sample spotting technology for successful identification of drug in mouse lung tissue by using MALDI-Orbitrap instrumentation. Copyright 2010 Elsevier B.V. All rights reserved.

Caffeic Acid Phenethyl Ester: A Review of Its Antioxidant Activity, Protective Effects against Ischemia-reperfusion Injury and Drug Adverse Reactions.

PubMed

Tolba, Mai F; Omar, Hany A; Azab, Samar S; Khalifa, Amani E; Abdel-Naim, Ashraf B; Abdel-Rahman, Sherif Z

2016-10-02

Propolis, a honey bee product, has been used in folk medicine for centuries for the treatment of abscesses, canker sores and for wound healing. Caffeic acid phenethyl ester (CAPE) is one of the most extensively investigated active components of propolis which possess many biological activities, including antibacterial, antiviral, antioxidant, anti-inflammatory, and anti-cancer effects. CAPE is a polyphenolic compound characterized by potent antioxidant and cytoprotective activities and protective effects against ischemia-reperfusion (I/R)-induced injury in multiple tissues such as brain, retina, heart, skeletal muscles, testis, ovaries, intestine, colon, and liver. Furthermore, several studies indicated the protective effects of CAPE against chemotherapy-induced adverse drug reactions (ADRs) including several antibiotics (streptomycin, vancomycin, isoniazid, ethambutol) and chemotherapeutic agents (mitomycin, doxorubicin, cisplatin, methotrexate). Due to the broad spectrum of pharmacological activities of CAPE, this review makes a special focus on the recently published data about CAPE antioxidant activity as well as its protective effects against I/R-induced injury and many adverse drug reactions.

Optoelectronic devices incorporating fluoropolymer compositions for protection

DOEpatents

Chen, Xuming; Chum, Pak-Wing S.; Howard, Kevin E.; Lopez, Leonardo C.; Sumner, William C.; Wu, Shaofu

2015-12-22

The fluoropolymer compositions of the present invention generally incorporate ingredients comprising one or more fluoropolymers, an ultraviolet light protection component (hereinafter UV protection component), and optionally one or more additional ingredients if desired. The UV protection component includes a combination of at least one hindered tertiary amine (HTA) compound having a certain structure and a weight average molecular weight of at least 1000. This tertiary amine is used in combination with at least one organic, UV light absorbing compound (UVLA compound) having a weight average molecular weight greater than 500. When the HTA compound and the UVLA compound are selected according to principles of the present invention, the UV protection component provides fluoropolymer compositions with significantly improved weatherability characteristics for protecting underlying materials, features, structures, components, and/or the like. In particular, fluoropolymer compositions incorporating the UV protection component of the present invention have unexpectedly improved ability to resist blackening, coloration, or other de gradation that may be caused by UV exposure. As a consequence, devices protected by these compositions would be expected to have dramatically improved service life. The compositions have a wide range of uses but are particularly useful for forming protective layers in optoelectronic devices.

An ecotoxicological approach to evaluate the effects of tourism impacts in the Marine Protected Area of La Maddalena (Sardinia, Italy).

PubMed

Moschino, V; Schintu, M; Marrucci, A; Marras, B; Nesto, N; Da Ros, L

2017-09-15

In the Marine Protected Area of La Maddalena Archipelago, environmental protection rules and safeguard measures for nautical activities have helped in reducing anthropogenic pressure; however, tourism related activities remain particularly significant in summer. With the aim of evaluating their impacts, the biomarker approach using transplanted Mytilus galloprovincialis as sentinel organisms coupled with POCIS deployment was applied. Mussels, translocated to four marine areas differently impacted by tourism activities, were sampled before, during and after the tourist season. Moreover, endocrine disruptors in passive samplers POCIS and the cellular toxicity of whole POCIS extracts on mussel haemocytes were evaluated to integrate ecotoxicological information. Lysosomal biomarkers, condition index and mortality rate, as well as metals in tissues suggested an alteration of the health status of mussels transplanted to the most impacted sites. The cellular toxicity of POCIS extracts was pointed out, notwithstanding the concentrations of the examined compounds were always below the detection limits. Copyright © 2017 Elsevier Ltd. All rights reserved.

Basics of Compounding: Compounding Irrigation Solutions for Sterile and Nonsterile Preparations.

PubMed

Allen, Loyd V

2017-01-01

Compounding pharmacists are sometimes called upon to prepare irrigation solutions, especially in the hospital or clinical setting. Irrigations are indicated for washing or bathing surgical incisions, wounds, and body tissues, including body cavities. Some irrigation solutions coming in contact with exposed tissue, must meet stringent requirements of sterility and bacterial endotoxins. Compounded irrigation solutions may involve wound(s), the bladder, and also may be for ophthalmic, otic, and nasal application. Some vaginal douches/instillations and rectal solutions may also be used as irrigations. As with any medication administered to the body or used on body tissues, there are requirements, and these may vary depending on the type of irrigation solution involved. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Antioxidant Action of Mangrove Polyphenols against Gastric Damage Induced by Absolute Ethanol and Ischemia-Reperfusion in the Rat

PubMed Central

de-Faria, Felipe Meira; Almeida, Ana Cristina Alves; Luiz-Ferreira, Anderson; Takayama, Christiane; Dunder, Ricardo José; da Silva, Marcelo Aparecido; Salvador, Marcos José; Abdelnur, Patrícia Verardi; Eberlin, Marcos Nogueira; Vilegas, Wagner; Toma, Walber; Souza-Brito, Alba Regina Monteiro

2012-01-01

Rhizophora mangle, the red mangrove, has long been known as a traditional medicine. Its bark has been used as astringent, antiseptic, hemostatic, with antifungic and antiulcerogenic properties. In this paper, we aimed to evaluate the antioxidant properties of a buthanolic fraction of the R. mangle bark extract (RM) against experimental gastric ulcer in rats. Unib-Wh rats received pretreatment of R. mangle after the induction of gastric injury with absolute ethanol and ischemia-reperfusion. Gastric tissues from both methods were prepared to the enzymatic assays, the levels of sulfhydril compounds (GSH), lipid peroxides (LPO), and the activities of glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and myeloperoxidase (MPO) were measured. The RM protected the gastric mucosa in both methods used, ethanol-induced gastric ulcer and ischemia-reperfusion, probably, by modulating the activities of the enzymes SOD, GPx, and GR and increasing or maintaining the levels of GSH; in adittion, LPO levels were reduced. The results suggest that the RM antioxidant activity leads to tissue protection; thus one of the antiulcer mechanisms present on the pharmacological effects of R. mangle is the antioxidant property. PMID:22654592

Protective Effect of Aronia Melanocarpa Polyphenols on Cadmium Accumulation in the Body: A Study in a Rat Model of Human Exposure to this Metal.

PubMed

Brzoska, Malgorzata M; Galazyn-Sidorczuk, Malgorzata; Jurczuk, Maria; Tomczyk, Michal

2015-01-01

Recently a growing attention has been paid to the possibility of using biologically active compounds, including polyphenols, for the prevention of unfavourable effects of exposure to xenobiotics. The study was aimed to investigate, in a female rat model, whether consumption of Aronia melanocarpa polyphenols (AMP) under chronic exposure to cadmium (Cd) decreases the gastrointestinal absorption and body burden of this heavy metal. For this purpose, Cd turnover (apparent absorption, retention in the body, concentration in the blood, soft tissues and bone tissue, total pool in internal organs, faecal and urinary excretion) was evaluated in the female Wistar rats who were administered only a 0.1% aqueous extract of AMP (prepared from the powdered extract containing 65.74% of polyphenols) as drinking fluid or/and Cd in diet (1 and 5 mg/kg) for up to 24 months. AMP administration under the low Cd treatment (1 mg/kg diet) had only a very slight protective impact against this metal accumulation in the organism, whereas polyphenols application under moderate exposure (5 mg Cd/kg diet) significantly decreased apparent absorption and retention in the body, and increased urinary concentration of this xenobiotic, resulting in its lower concentration in the blood and lower accumulation in soft tissues (mainly in the liver and kidneys) and bone tissue. Based on the study, it can be concluded that consumption of polyphenol- rich products may prevent Cd absorption from the diet polluted by this metal and its accumulation in the females' body, and thus also prevent its toxic action.

Elicitation: a tool for enriching the bioactive composition of foods.

PubMed

Baenas, Nieves; García-Viguera, Cristina; Moreno, Diego A

2014-09-01

Elicitation is a good strategy to induce physiological changes and stimulate defense or stress-induced responses in plants. The elicitor treatments trigger the synthesis of phytochemical compounds in fruits, vegetables and herbs. These metabolites have been widely investigated as bioactive compounds responsible of plant cell adaptation to the environment, specific organoleptic properties of foods, and protective effects in human cells against oxidative processes in the development of neurodegenerative and cardiovascular diseases and certain types of cancer. Biotic (biological origin), abiotic (chemical or physical origin) elicitors and phytohormones have been applied alone or in combinations, in hydroponic solutions or sprays, and in different selected time points of the plant growth or during post-harvest. Understanding how plant tissues and their specific secondary metabolic pathways respond to specific treatments with elicitors would be the basis for designing protocols to enhance the production of secondary metabolites, in order to produce quality and healthy fresh foods.

Identification of polychlorinated styrene compounds in heron tissues by gas-liquid chromatography-mass spectrometry

USGS Publications Warehouse

Reichel, W.L.; Prouty, R.M.; Gay, M.L.

1977-01-01

Unknown compounds detected in Ardea herodias tissues are identified by gas-liquid chromatography-mass spectrometry as residues of octachlorostyrene. Heptachlorostyrene and hexachlorostyrene were tentatively identified.

Content changes of bitter compounds in 'Guoqing No.1' Satsuma mandarin (Citrus unshiu Marc.) during fruit development of consecutive 3 seasons.

PubMed

Li, Shaojie; Wang, Zhuang; Ding, Fan; Sun, Da; Ma, Zhaocheng; Cheng, Yunjiang; Xu, Juan

2014-02-15

The main bitter compounds (nomilin, limonin and naringin) in the fruit tissues of 'Guoqing No.1' Satsuma mandarin (Citrus unshiu Marc.) were determined throughout the fruit development of 3 consecutive growing seasons. Although fluctuating largely at the corresponding developing stages of the 3 years, the contents of these compounds in fruit tissues mostly displayed a declining trend, which implied that the rhythm of the metabolism of these bitter compounds was not consistent among years and was largely growing season dependent. Regarding their distribution, fruit flavedo might be a weak sink that contained the lowest level of naringin, while the segment membrane accumulated large amount of limonin and nomilin, which indicated a possible tissue bias pattern for biosynthesis or accumulation of those compounds. Partial correlation coefficient analysis revealed a synergistic accumulation of naringin and the two limonoid aglycones in fruit tissues during fruit development, indicating an integrated metabolism of flavonoids and limonoids. Copyright © 2013 Elsevier Ltd. All rights reserved.

Systemic Induction of the Small Antibacterial Compound in the Leaf Exudate During Benzothiadiazole-elicited Systemic Acquired Resistance in Pepper

PubMed Central

Lee, Boyoung; Park, Yong-Soon; Yi, Hwe-Su; Ryu, Choong-Min

2013-01-01

Plants protect themselves from diverse potential pathogens by induction of the immune systems such as systemic acquired resistance (SAR). Most bacterial plant pathogens thrive in the intercellular space (apoplast) of plant tissues and cause symptoms. The apoplastic leaf exudate (LE) is believed to contain nutrients to provide food resource for phytopathogenic bacteria to survive and to bring harmful phytocompounds to protect plants against bacterial pathogens. In this study, we employed the pepper-Xanthomonas axonopodis system to assess whether apoplastic fluid from LE in pepper affects the fitness of X. axonopodis during the induction of SAR. The LE was extracted from pepper leaves 7 days after soil drench-application of a chemical trigger, benzothiadiazole (BTH). Elicitation of plant immunity was confirmed by significant up-regulation of four genes, CaPR1, CaPR4, CaPR9, and CaCHI2, by BTH treatment. Bacterial fitness was evaluated by measuring growth rate during cultivation with LE from BTH- or water-treated leaves. LE from BTH-treatment significantly inhibited bacterial growth when compared to that from the water-treated control. The antibacterial activity of LE from BTH-treated samples was not affected by heating at 100°C for 30 min. Although the antibacterial molecules were not precisely identified, the data suggest that small (less than 5 kDa), heat-stable compound(s) that are present in BTH-induced LE directly attenuate bacterial growth during the elicitation of plant immunity. PMID:25288963

Spatiotemporal monitoring of the antibiome secreted by Bacillus biofilms on plant roots using MALDI mass spectrometry imaging.

PubMed

Debois, Delphine; Jourdan, Emmanuel; Smargiasso, Nicolas; Thonart, Philippe; De Pauw, Edwin; Ongena, Marc

2014-05-06

Some soil Bacilli living in association with plant roots can protect their host from infection by pathogenic microbes and are therefore being developed as biological agents to control plant diseases. The plant-protective activity of these bacteria has been correlated with the potential to secrete a wide array of antibiotic compounds upon growth as planktonic cells in isolated cultures under laboratory conditions. However, in situ expression of these antibiotics in the rhizosphere where bacterial cells naturally colonize root tissues is still poorly understood. In this work, we used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) to examine spatiotemporal changes in the secreted antibiome of Bacillus amyloliquefaciens developing as biofilms on roots. Nonribosomal lipopeptides such as the plant immunity elicitor surfactin or the highly fungitoxic iturins and fengycins were readily produced albeit in different time frames and quantities in the surrounding medium. Interestingly, tandem mass spectrometry (MS/MS) experiments performed directly from the gelified culture medium also allowed us to identify a new variant of surfactins released at later time points. However, no other bioactive compounds such as polyketides were detected at any time, strongly suggesting that the antibiome expressed in planta by B. amyloliquefaciens does not reflect the vast genetic arsenal devoted to the formation of such compounds. This first dynamic study reveals the power of MALDI MSI as tool to identify and map antibiotics synthesized by root-associated bacteria and, more generally, to investigate plant-microbe interactions at the molecular level.

Synthesis and biological evaluation of radio and dye labeled amino functionalized dendritic polyglycerol sulfates as multivalent anti-inflammatory compounds.

PubMed

Gröger, Dominic; Paulus, Florian; Licha, Kai; Welker, Pia; Weinhart, Marie; Holzhausen, Cornelia; Mundhenk, Lars; Gruber, Achim D; Abram, Ulrich; Haag, Rainer

2013-09-18

Herein we describe a platform technology for the synthesis and characterization of partially aminated, (35)S-labeled, dendritic polyglycerol sulfate (dPG(35)S amine) and fluorescent dPGS indocarbocyanine (ICC) dye conjugates. These polymer conjugates, based on a biocompatible dendritic polyglycerol scaffold, exhibit a high affinity to inflamed tissue in vivo and represent promising candidates for therapeutic and diagnostic applications. By utilizing a one-step sequential copolymerization approach, dendritic polyglycerol (Mn ≈ 4.5 kDa) containing 9.4% N-phthalimide protected amine functionalities was prepared on a large scale. Sulfation and simultaneous radio labeling with (35)SO3 pyridine complex, followed by cleavage of the N-phthalimide protecting groups, yielded dPG(35)S amine as a beta emitting, inflammation specific probe with free amino functionalities for conjugation. Furthermore, efficient labeling procedures with ICC via iminothiolane modification and subsequent "Michael" addition of the maleimide functionalized ICC dye, as well as by amide formation via NHS derivatized ICC on a dPGS amine scaffold, are described. The dPGS-ICC conjugates were investigated with respect to their photophysical properties, and both the radiolabeled and fluorescent compounds were comparatively visualized in histological tissue sections (radio detection and fluorescence microscopy) of animals treated with dPGS. Furthermore, cellular uptake of dPGS-ICC was found in endothelial cord blood (HUVEC) and the epithelial lung cells (A549). The presented synthetic routes allow a reproducible, controlled synthesis of dPGS amine on kilogram scale applying a one-pot batch reaction process. dPGS amine can be used for analysis via radioactivity or fluorescence, thereby creating a new platform for inflammation specific, multimodal imaging purposes using other attachable probes or contrast agents.

Anti-inflammatory effects of nitric oxide-releasing hydrocortisone NCX 1022, in a murine model of contact dermatitis

PubMed Central

Hyun, Eric; Bolla, Manlio; Steinhoff, Martin; Wallace, John L; Soldato, Piero del; Vergnolle, Nathalie

2004-01-01

The concept that nitric oxide (NO) release can be beneficial in inflammatory conditions has raised more attention in the recent years, particularly with the development of nitric oxide-releasing anti-inflammatory drugs. There is considerable evidence that NO is capable of enhancing the anti-inflammatory benefits of conventional anti-inflammatory drugs. Since hydrocortisone is the most widely used anti-inflammatory drug for the treatment of skin inflammation, we compared the anti-inflammatory effects of hydrocortisone to an NO-releasing derivative of hydrocortisone, NCX 1022, in a murine model of irritant contact dermatitis, induced by epidermal application of benzalkonium chloride. Topical pre- and post-treatment with NCX 1022 (3 nmol) in C57BL6 mice not only reduced ear oedema formation in a dose-dependent manner, but also was significantly more effective than the parent compound during the initial stages of inflammation (from 1 to 5 h). NCX 1022, but not hydrocortisone, significantly inhibited granulocyte recruitment (tissue myeloperoxidase activity). Histological samples of mouse ears treated with NCX 1022 showed significant reduction in both the number of infiltrated cells and disruption of the tissue architecture compared to hydrocortisone-treated tissues. With intravital microscopy, we observed that both pre- and post-treatments with NCX 1022 were more effective than hydrocortisone in terms of inhibiting benzalkonium chloride-induced leukocyte adhesion to the endothelium, without affecting the flux of rolling leukocytes or venule diameter. These results suggest that by releasing NO, NCX 1022 modulates one of the early events of skin inflammation: the recruitment of leukocytes to the site of inflammation. Overall, we have shown that NO-hydrocortisone provided faster and greater protective effects, reducing major inflammatory parameters (leukocyte adhesion and recruitment, oedema formation, tissue disruption) compared to its parental compound. PMID:15313880

Anti-inflammatory effects of nitric oxide-releasing hydrocortisone NCX 1022, in a murine model of contact dermatitis.

PubMed

Hyun, Eric; Bolla, Manlio; Steinhoff, Martin; Wallace, John L; Soldato, Piero Del; Vergnolle, Nathalie

2004-11-01

1 The concept that nitric oxide (NO) release can be beneficial in inflammatory conditions has raised more attention in the recent years, particularly with the development of nitric oxide-releasing anti-inflammatory drugs. There is considerable evidence that NO is capable of enhancing the anti-inflammatory benefits of conventional anti-inflammatory drugs. 2 Since hydrocortisone is the most widely used anti-inflammatory drug for the treatment of skin inflammation, we compared the anti-inflammatory effects of hydrocortisone to an NO-releasing derivative of hydrocortisone, NCX 1022, in a murine model of irritant contact dermatitis, induced by epidermal application of benzalkonium chloride. 3 Topical pre- and post-treatment with NCX 1022 (3 nmol) in C57BL6 mice not only reduced ear oedema formation in a dose-dependent manner, but also was significantly more effective than the parent compound during the initial stages of inflammation (from 1 to 5 h). NCX 1022, but not hydrocortisone, significantly inhibited granulocyte recruitment (tissue myeloperoxidase activity). Histological samples of mouse ears treated with NCX 1022 showed significant reduction in both the number of infiltrated cells and disruption of the tissue architecture compared to hydrocortisone-treated tissues. 4 With intravital microscopy, we observed that both pre- and post-treatments with NCX 1022 were more effective than hydrocortisone in terms of inhibiting benzalkonium chloride-induced leukocyte adhesion to the endothelium, without affecting the flux of rolling leukocytes or venule diameter. 5 These results suggest that by releasing NO, NCX 1022 modulates one of the early events of skin inflammation: the recruitment of leukocytes to the site of inflammation. Overall, we have shown that NO-hydrocortisone provided faster and greater protective effects, reducing major inflammatory parameters (leukocyte adhesion and recruitment, oedema formation, tissue disruption) compared to its parental compound.

Photosynthetic capacity is negatively correlated with the concentration of leaf phenolic compounds across a range of different species

PubMed Central

Sumbele, Sally; Fotelli, Mariangela N.; Nikolopoulos, Dimosthenis; Tooulakou, Georgia; Liakoura, Vally; Liakopoulos, Georgios; Bresta, Panagiota; Dotsika, Elissavet; Adams, Mark A.; Karabourniotis, George

2012-01-01

Background and aims Phenolic compounds are the most commonly studied of all secondary metabolites because of their significant protective–defensive roles and their significant concentration in plant tissues. However, there has been little study on relationships between gas exchange parameters and the concentration of leaf phenolic compounds (total phenolics (TP) and condensed tannins (CT)) across a range of species. Therefore, we addressed the question: is there any correlation between photosynthetic capacity (Amax) and TP and CT across species from different ecosystems in different continents? Methodology A plethora of functional and structural parameters were measured in 49 plant species following different growth strategies from five sampling sites located in Greece and Australia. The relationships between several leaf traits were analysed by means of regression and principal component analysis. Principal results The results revealed a negative relationship between TP and CT and Amax among the different plant species, growth strategies and sampling sites, irrespective of expression (with respect to mass, area or nitrogen content). Principal component analysis showed that high concentrations of TP and CT are associated with thick, dense leaves with low nitrogen. This leaf type is characterized by low growth, Amax and transpiration rates, and is common in environments with low water and nutrient availability, high temperatures and high light intensities. Therefore, the high TP and CT in such leaves are compatible with the protective and defensive functions ascribed to them. Conclusions Our results indicate a functional integration between carbon gain and the concentration of leaf phenolic compounds that reflects the trade-off between growth and defence/protection demands, depending on the growth strategy adopted by each species. PMID:23050073

Thiopental Inhibits Global Protein Synthesis by Repression of Eukaryotic Elongation Factor 2 and Protects from Hypoxic Neuronal Cell Death

PubMed Central

Schwer, Christian I.; Lehane, Cornelius; Guelzow, Timo; Zenker, Simone; Strosing, Karl M.; Spassov, Sashko; Erxleben, Anika; Heimrich, Bernd; Buerkle, Hartmut; Humar, Matjaz

2013-01-01

Ischemic and traumatic brain injury is associated with increased risk for death and disability. The inhibition of penumbral tissue damage has been recognized as a target for therapeutic intervention, because cellular injury evolves progressively upon ATP-depletion and loss of ion homeostasis. In patients, thiopental is used to treat refractory intracranial hypertension by reducing intracranial pressure and cerebral metabolic demands; however, therapeutic benefits of thiopental-treatment are controversially discussed. In the present study we identified fundamental neuroprotective molecular mechanisms mediated by thiopental. Here we show that thiopental inhibits global protein synthesis, which preserves the intracellular energy metabolite content in oxygen-deprived human neuronal SK-N-SH cells or primary mouse cortical neurons and thus ameliorates hypoxic cell damage. Sensitivity to hypoxic damage was restored by pharmacologic repression of eukaryotic elongation factor 2 kinase. Translational inhibition was mediated by calcium influx, activation of the AMP-activated protein kinase, and inhibitory phosphorylation of eukaryotic elongation factor 2. Our results explain the reduction of cerebral metabolic demands during thiopental treatment. Cycloheximide also protected neurons from hypoxic cell death, indicating that translational inhibitors may generally reduce secondary brain injury. In conclusion our study demonstrates that therapeutic inhibition of global protein synthesis protects neurons from hypoxic damage by preserving energy balance in oxygen-deprived cells. Molecular evidence for thiopental-mediated neuroprotection favours a positive clinical evaluation of barbiturate treatment. The chemical structure of thiopental could represent a pharmacologically relevant scaffold for the development of new organ-protective compounds to ameliorate tissue damage when oxygen availability is limited. PMID:24167567

Sea Buckthorn Leaf Extract Protects Jejunum and Bone Marrow of 60Cobalt-Gamma-Irradiated Mice by Regulating Apoptosis and Tissue Regeneration

PubMed Central

Gupta, Manish; Saini, Manu; Abdin, M. Z.; Prasad, Jagdish

2015-01-01

A single dose (30 mg/kg body weight) of standardized sea buckthorn leaf extract (SBL-1), administered 30 min before whole body 60Co-gamma-irradiation (lethal dose, 10 Gy), protected >90% of mice population. The purpose of this study was to investigate the mechanism of action of SBL-1 on jejunum and bone marrow, quantify key bioactive compounds, and analyze chemical composition of SBL-1. Study with 9-week-old inbred male Swiss albino Strain ‘A' mice demonstrated that SBL-1 treatment before 60Co-gamma-irradiation (10 Gy) significantly (p < 0.05) countered radiation induced decreases in jejunum crypts (1.27-fold), villi number (1.41-fold), villus height (1.25-fold), villus cellularity (2.27-fold), cryptal Paneth cells (1.89-fold), and Bcl2 level (1.54-fold). It countered radiation induced increases in cryptal apoptotic cells (1.64-fold) and Bax levels (1.88-fold). It also countered radiation (2 Gy and 3 Gy) induced bone marrow apoptosis (1.59-fold and 1.85-fold) and micronuclei frequency (1.72-fold and 2.6-fold). SBL-1 rendered radiation protection by promoting cryptal stem cells proliferation, by regulating apoptosis, and by countering radiation induced chromosomal damage. Quercetin, Ellagic acid, Gallic acid, high contents polyphenols, tannins, and thiols detected in SBL-1 may have contributed to radiation protection by neutralization of radiation induced oxidative species, supporting stem cell proliferation and tissue regeneration. PMID:26421051

Skin protection against UV light by dietary antioxidants.

PubMed

Fernández-García, Elisabet

2014-09-01

There is considerable interest in the concept of additional endogenous photoprotection by dietary antioxidants. A number of efficient micronutrients are capable of contributing to the prevention of UV damage in humans. These compounds protect molecular targets by scavenging reactive oxygen species, including excited singlet oxygen and triplet state molecules, and also modulate stress-dependent signaling and/or suppress cellular and tissue responses like inflammation. Micronutrients present in the diet such as carotenoids, vitamins E and C, and polyphenols contribute to antioxidant defense and may also contribute to endogenous photoprotection. This review summarizes the literature concerning the use of dietary antioxidants as systemic photoprotective agents towards skin damage induced by UVA and UVB. Intervention studies in humans with carotenoid-rich diets have shown photoprotection. Interestingly, rather long treatment periods (a minimum of 10 weeks) were required to achieve this effect. Likewise, dietary carotenoids exert their protective antioxidant function in several in vitro and in vivo studies when present at sufficiently high concentration. A combination of vitamins E and C protects the skin against UV damage. It is suggested that daily consumption of dietary polyphenols may provide efficient protection against the harmful effects of solar UV radiation in humans. Furthermore, the use of these micronutrients in combination may provide an effective strategy for protecting human skin from damage by UV exposure.

Effect of Compound 21, a Selective Angiotensin II Type 2 Receptor Agonist, in a Murine Xenograft Model of Dupuytren Disease.

PubMed

Chisholm, Jessica; Gareau, Alison J; Byun, Stephanie; Paletz, Justin L; Tang, David; Williams, Jason; LeVatte, Terry; Bezuhly, Michael

2017-11-01

Although surgical excision and intralesional collagenase injection are mainstays in Dupuytren disease treatment, no effective medical therapy exists for recurrent disease. Compound 21, a selective agonist of the angiotensin II type 2 receptor, has been shown to protect against fibrosis in models of myocardial infarction and stroke. The authors investigated the potential use of compound 21 in the treatment of Dupuytren disease. Human dermal fibroblasts were treated in vitro with compound 21 and assessed for viability using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, migration by means of scratch assay, and profibrotic gene transcription by means of quantitative reverse transcription polymerase chain reaction. Compound 21 effects in vivo were assessed using a xenograft model. Dupuytren disease cord specimens from patients undergoing open partial fasciectomy were divided into two segments. Segments were implanted under the dorsal skin of nude mouse pairs. Beginning on day 5, one mouse from each pair received daily intraperitoneal injections of compound 21 (10 μg/kg/day), and the other received vehicle. On day 10, segments were explanted and submitted for immunohistochemistry. Human dermal fibroblasts treated with compound 21 displayed decreased migration and decreased gene expression of connective tissue growth factor, fibroblast specific protein-1, transforming growth factor-β1, Smad3, and Smad4. Dupuytren disease segments from compound 21-treated mice demonstrated significantly reduced alpha-smooth muscle actin and Ki67 staining, with increased density of CD31 staining vessels. Compound 21 significantly decreases expression of profibrotic genes and decreases myofibroblast proliferation as indicated by reduced Ki67 and alpha-smooth muscle actin expression. These findings support compound 21 as a potential novel treatment modality for Dupuytren disease.

CLOSED-LOOP STRIPPING ANALYSIS (CLSA) OF SYNTHETIC MUSK COMPOUNDS FROM FISH TISSUES WITH MEASUREMENT BY OC/MS/SIM

EPA Science Inventory

Synthetic musk compounds are used as inexpensive fragrance materials for the production
of perfumes and as additives to soap, detergent, and shampoo. They have been found in surface water, fish tissues, and human breast milk. The ubiquity of this class of compounds in the env...

The novel cyclophilin D inhibitor compound 19 protects retinal pigment epithelium cells and retinal ganglion cells from UV radiation.

PubMed

Xie, Laiqing; Cheng, Long; Xu, Guoxu; Zhang, Ji; Ji, Xiaoyan; Song, E

2017-06-10

Excessive Ultra violet (UV) radiation induces injuries to retinal pigment epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs), causing retinal degeneration. Cyclophilin D (Cyp-D)-dependent mitochondrial permeability transition pore (mPTP) opening mediates UV-induced cell death. In this study, we show that a novel Cyp-D inhibitor compound 19 efficiently protected RPEs and RGCs from UV radiation. Compound 19-mediated cytoprotection requires Cyp-D, as it failed to further protect RPEs/RGCs from UV when Cyp-D was silenced by targeted shRNAs. Compound 19 almost blocked UV-induced p53-Cyp-D mitochondrial association, mPTP opening and subsequent cytochrome C release. Further studies showed that compound 19 inhibited UV-induced reactive oxygen species (ROS) production, lipid peroxidation and DNA damage. Together, compound 19 protects RPEs and RGCs from UV radiation, possibly via silencing Cyp-D-regulated intrinsic mitochondrial death pathway. Compound 19 could a lead compound for treating UV-associated retinal degeneration diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Bioreactor Steroid Production and Analysis of Date Palm Embryogenic Callus.

PubMed

El-Sharabasy, Sherif; El-Dawayati, Maiada

2017-01-01

Several compounds and families of compounds of date palm secondary metabolites have been investigated. The analysis of date palm tissue has shown the abundance of secondary metabolites including phytosterols, e.g., steroids, an important group of pharmaceutical compounds. Biotechnology offers the opportunity to utilize cells, tissues, and organs grown in vitro and manipulated to obtain desired compounds. This chapter presents a protocol for the production, determination, and identification of steroids in date palm callus tissue. The addition of 0.01 mg/L pyruvic acid as a precursor to MS liquid culture medium enhances steroid production. In addition, the chapter describes the sterol analytical techniques based on gas-liquid chromatography and gas chromatography-mass spectrometry.

Polyphenolic compounds with antioxidant potential and neuro-protective effect from Cimicifuga dahurica (Turcz.) Maxim.

PubMed

Qin, Rulan; Zhao, Ying; Zhao, Yudan; Zhou, Wanrong; Lv, Chongning; Lu, Jincai

2016-12-01

Three new phenolic compounds (1-3), along with five known compounds (4-8) were isolated from the rhizome of Cimicifuga dahurica (Turcz.) Maxim. Their structures were elucidated by spectroscopic methods including 1D-NMR, 2D-NMR and HR-MS techniques. DPPH method and protective effect on PC12 cells against H 2 O 2 -induced oxidative damage model were carried to evaluate the antioxidant capability of these compounds. Compound 5 showed significant antioxidant activity with IC 50 values 9.33μM in DPPH assay and compound 2 displayed marked neuro-protective effect with 87.65% cell viability at the concentration of 10μM. Additionally, the possible structure-activity relationships of these phenolic compounds were tentatively discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Toxicity reference values for protecting aquatic birds in China from the effects of polychlorinated biphenyls.

PubMed

Su, Hailei; Wu, Fengchang; Zhang, Ruiqing; Zhao, Xiaoli; Mu, Yunsong; Feng, Chenglian; Giesy, John P

2014-01-01

PCBs are typical of persistent, bioaccumulative and toxic compounds (PBTs) that are widely distributed in the environment and can biomagnify through aquatic food webs, because of their stability and lipophilic properties. Fish-eating birds are top predators in the aquatic food chain and may suffer adverse effects from exposure to PCB concentrations. In this review, we address the toxicity of PCBs to birds and have derived tissue residue guidelines (TRGs) and toxic reference values (TRVs) for PCBs for protecting birds in China. In deriving these protective indices, we utilized available data and three approaches, to wit: species sensitivity distribution (SSD), critical study approach (CSA) and toxicity percentile rank method (TPRM). The TRGs and TRVs arrived at by using these methods were 42.3, I 0. 7, 4.3 pg TEQs/g diet wm and 16.7, 15.5, and 5.5 pg TEQs/g tissue wm for the CSA SSD and TPRM approaches, respectively. These criteria values were analyzed and compared with those derived by others. The following TRG and TRY, derived by SSD, were recommended as avian criteria for protecting avian species in China: 10.7 pg TEQs/g diet wm and 15.5 pg TEQs/g tissue wm, respectively. The hazard of PCBs to birds was assessed by comparing the TRVs and TRGs derived in this study with actual PCB concentrations detected in birds or fish. The criteria values derived in this study can be used to evaluate the risk of PCBs to birds in China, and to provide indices that are more reasonable for protecting Chinese avian species. However, several sources of uncertainty exists when deriving TRGs and TRVs for the PCBs in birds, such as lack of adequate toxicity data for birds and need to use uncertainty factors. Clearly, relevant work on PCBs and birds in China are needed in the future. For example, PCB toxicity data for resident avian species in China are needed. In addition, studies are needed on the actual PCB levels in birds and fish in China. Such information is needed to serve as a more firm foundation for future risk assessments.

40 CFR Appendix Vi to Part 265 - Compounds With Henry's Law Constant Less Than 0.1 Y/X

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 27 2013-07-01 2013-07-01 false Compounds With Henry's Law Constant Less Than 0.1 Y/X VI Appendix VI to Part 265 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Law Constant Less Than 0.1 Y/X Compound name CAS No. Acetaldol 107-89-1 Acetamide 60-35-5 2...

40 CFR Appendix Vi to Part 265 - Compounds With Henry's Law Constant Less Than 0.1 Y/X

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Compounds With Henry's Law Constant Less Than 0.1 Y/X VI Appendix VI to Part 265 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Law Constant Less Than 0.1 Y/X Compound name CAS No. Acetaldol 107-89-1 Acetamide 60-35-5 2...

40 CFR Appendix Vi to Part 265 - Compounds With Henry's Law Constant Less Than 0.1 Y/X

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Compounds With Henry's Law Constant Less Than 0.1 Y/X VI Appendix VI to Part 265 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Law Constant Less Than 0.1 Y/X Compound name CAS No. Acetaldol 107-89-1 Acetamide 60-35-5 2...

40 CFR Appendix Vi to Part 265 - Compounds With Henry's Law Constant Less Than 0.1 Y/X

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 27 2012-07-01 2012-07-01 false Compounds With Henry's Law Constant Less Than 0.1 Y/X VI Appendix VI to Part 265 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Law Constant Less Than 0.1 Y/X Compound name CAS No. Acetaldol 107-89-1 Acetamide 60-35-5 2...

40 CFR Appendix Vi to Part 265 - Compounds With Henry's Law Constant Less Than 0.1 Y/X

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Compounds With Henry's Law Constant Less Than 0.1 Y/X VI Appendix VI to Part 265 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Law Constant Less Than 0.1 Y/X Compound name CAS No. Acetaldol 107-89-1 Acetamide 60-35-5 2...

STUDIES ON THE DISTRIBUTION AND PHOSPHATE TURNOVER OF THE ACID-SOLUBLE PHOSPHORUS COMPOUNDS IN VARIOUS NORMAL AND NEOPLASTIC TISSUES OF RATS. I. A SEMI-MICRO GRADIENT ELUTION CHROMATOGRAPHY WITH DOWEX FORMATE AND IDENTIFICATION OF SOME PHOSPHATE ESTERS ON THE CHROMATOGRAM (ENGLISH TEXT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horie, S.; Terada, S.

A modified semi-micro gradient elution chromatography for the analysis of tissue acid-soluble phosphorus compounds is described. One to 3 g of tissue can be analyzed by this method. Liver, muscle, and thymus tissue of rats were analyzed and the chromatograms are illustrated. The distribution and turnover of the acid-soluble phosphorus compounds in rat liver were also studied by P/sup 32/ injection and the use of the semi-micro method. Glucose 6-phosphate and L- alpha -glycerophosphate were identified on the chromatogram, and a phosphorus compound containing aminoacid was separated from the dowex 1 formate non-adsorbable fraction. (Abstr. Japan Med., 1: No. 9,more » 1961)« less

Apollo 12 lunar material - Effects on lipid levels of tobacco tissue cultures.

NASA Technical Reports Server (NTRS)

Weete, J. D.; Walkinshaw, C. H.; Laseter, J. L.

1972-01-01

Tobacco tissue cultures grown in contact with lunar material from Apollo 12, for a 12-week period, resulted in fluctuations of both the relative and absolute concentrations of endogenous sterols and fatty acids. The experimental tissues contained higher concentrations of sterols than the controls did. The ratio of campesterol to stigmasterol was greater than 1 in control tissues, but less than 1 in the experimental tissues after 3 weeks. High relative concentrations (17.1 to 22.2 per cent) of an unidentified compound or compounds were found only in control tissues that were 3 to 9 weeks of age.

Evaluation of the bioactive extract of actinomyces isolated from the Egyptian environment against aflatoxin B1-induce cytotoxicity, genotoxicity and oxidative stress in the liver of rats.

PubMed

El-Nekeety, Aziza A; Salman, Asmaa S; Hathout, Amal S; Sabry, Bassem A; Abdel-Aziem, Sekena H; Hassan, Nabila S; Abdel-Wahhab, Mosaad A

2017-07-01

This study aimed to determine the bioactive compounds of actinomyces (ACT) isolated from the Egyptian environment (D-EGY) and to evaluate their protective activity against AFB 1 in female Sprague-Dawley rats. Six groups of animals were treated orally for 3 weeks included: C, the control group, T1, AFB 1 -treated group (80 μg/kg b.w), T2 and T3, the groups received ACT extract at low (25 mg/kg b.w) or high (50 mg/kg b.w) doses, T4 and T5, the groups received AFB 1 plus the low or high dose of ACT extract. Blood, bone marrow and tissue samples were collected for different analyses and histological examination. The results revealed the identification of 40 components, representing 99.98%. Treatment with AFB 1 disturbs liver function parameters, oxidative stress markers, antioxidant gene expressions, DNA fragmentation and induced severe histological changes. ACT extract at the low or high doses did not induce significant changes in all the tested parameters or histological picture of the liver. Moreover, ACT extract succeeded to induce a significant protection against the toxicity of AFB 1 . It could be concluded that the bioactive compounds in ACT are promise candidate for the development of food additive or drugs for the protection and treatment of liver disorders in the endemic area. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oceanic protection of prebiotic organic compounds from UV radiation

NASA Technical Reports Server (NTRS)

Cleaves, H. J.; Miller, S. L.; Bada, J. L. (Principal Investigator)

1998-01-01

It is frequently stated that UV light would cause massive destruction of prebiotic organic compounds because of the absence of an ozone layer. The elevated UV flux of the early sun compounds this problem. This applies to organic compounds of both terrestrial and extraterrestrial origin. Attempts to deal with this problem generally involve atmospheric absorbers. We show here that prebiotic organic polymers as well as several inorganic compounds are sufficient to protect oceanic organic molecules from UV degradation. This aqueous protection is in addition to any atmospheric UV absorbers and should be a ubiquitous planetary phenomenon serving to increase the size of planetary habitable zones.

Thienopyrimidine-type compounds protect Arabidopsis plants against the hemibiotrophic fungal pathogen Colletotrichum higginsianum and bacterial pathogen Pseudomonas syringae pv. maculicola.

PubMed

Narusaka, Mari; Narusaka, Yoshihiro

2017-03-04

Plant activators activate systemic acquired resistance-like defense responses or induced systemic resistance, and thus protect plants from pathogens. We screened a chemical library composed of structurally diverse small molecules. We isolated six plant immune-inducing thienopyrimidine-type compounds and their analogous compounds. It was observed that the core structure of thienopyrimidine plays a role in induced resistance in plants. Furthermore, we highlight the protective effect of thienopyrimidine-type compounds against both hemibiotrophic fungal pathogen, Colletotrichum higginsianum, and bacterial pathogen, Pseudomonas syringae pv. maculicola, in Arabidopsis thaliana. We suggest that thienopyrimidine-type compounds could be potential lead compounds as novel plant activators, and can be useful and effective agrochemicals against various plant diseases.

Simultaneous UPLC-MS/MS analysis of native catechins and procyanidins and their microbial metabolites in intestinal contents and tissues of male Wistar Furth inbred rats.

PubMed

Goodrich, Katheryn M; Neilson, Andrew P

2014-05-01

Procyanidins have been extensively investigated for their potential health protective activities. However, the potential bioactivities of procyanidins are limited by their poor bioavailability. The majority of the ingested dose remains unabsorbed and reaches the colon where extensive microbial metabolism occurs. Most existing analytical methods measure either native compounds (catechins and procyanidins), or their microbial metabolites. The objectives of this study were to develop a high-throughput extraction and UPLC-MS/MS method for simultaneous measurement of both native procyanidins and their metabolites, facilitating high-throughput analysis of native and metabolite profiles in various regions of the colon. The present UPLC-MS/MS method facilitates simultaneous resolution and detection of authentic standards of 14 native catechin monomers and procyanidins, as well as 24 microbial metabolites. Detection and resolution of an additional 3 procyanidin dimers and 10 metabolites for which standards were not available was achieved. Elution and adequate resolution of both native compounds and metabolites were achieved within 10min. The intraday repeatability for native compounds was between 1.1 and 16.5%, and the interday repeatability for native compounds was between 2.2 and 25%. Intraday and interday repeatability for metabolites was between 0.6 and 24.1% and 1 and 23.9%, respectively. Observed lower limits of quantification for native compounds were ∼9-350fmol on-column, and for the microbial metabolites were ∼0.8-12,000fmol on-column. Observed lower limits of detection for native compounds were ∼4.5-190fmol on-column, and for metabolites were 0.304-6020fmol on-column. For native monomers and procyanidins, extraction recoveries ranged from 38 to 102%. Extraction recoveries for the 9 microbial metabolites tested ranged from 41 to 95%. Data from tissue analysis of rats gavaged with grape seed extract indicate fairly high accumulation of native compounds, primarily monomers and dimers, in the cecum and colon. Metabolite data indicate the progressive nature of microbial metabolism as the digesta moves through the lower GI tract. This method facilitates the high-throughput, sensitive, and simultaneous analysis of both native compounds and their microbial metabolites in biological samples and provides a more efficient means of extraction and analysis than previous methods. Copyright © 2014 Elsevier B.V. All rights reserved.

Novel TASK channels inhibitors derived from dihydropyrrolo[2,1-a]isoquinoline.

PubMed

Noriega-Navarro, R; Lopez-Charcas, O; Hernández-Enríquez, B; Reyes-Gutiérrez, P E; Martínez, R; Landa, A; Morán, J; Gomora, J C; Garcia-Valdes, J

2014-04-01

TASK channels belong to the family of K(+) channels with 4 transmembrane segments and 2 pore domains (4TM/2P) per subunit. These channels have been related to apoptosis in cerebellar granule neurons (CGN), as well as cancer in other tissues. TASK current is regulated by hormones, neurotransmitters, anesthetics and divalent cations, which are not selective. Recently, there has been found some organic compounds that inhibit TASK current selectively. In order to find other modulators, we report here a group of five dihydropyrrolo[2,1-a]isoquinolines (DPIs), four of them with putative anticancer activity, that were evaluated on TASK-1 and TASK-3 channels. The compounds 1, 2 and 3 showed IC50 < 320 μM on TASK-1 and TASK-3, intermediate activity on TASK-1/TASK-3 heterodimer, moderate effect over hslo and TREK-1 (500 μM), and practically not inhibition on Shaker-IR, herg and IRK2.1 potassium channels, when they were expressed heterologously in Xenopus laevis oocytes. In rat CGN, 500 μM of these three compounds induced a decrement by >39% of the TASK-carried leak current. Finally, only compound 1 showed significant protection (∼36%) against apoptotic death of CGN induced by K(+) deprivation. These results suggest that DPI compounds could be potential candidates for designing new selective inhibitors of TASK channels. Copyright © 2013 Elsevier Ltd. All rights reserved.

Boron attenuates malathion-induced oxidative stress and acetylcholinesterase inhibition in rats.

PubMed

Coban, Funda Karabag; Ince, Sinan; Kucukkurt, Ismail; Demirel, Hasan Huseyin; Hazman, Omer

2015-10-01

Organophosphorus compounds cause oxidative stress and lead to alterations in antioxidant status in organisms. In this study, the effects of subchronic exposure to malathion and the protective effects of boron (B) were evaluated in 48 Wistar rats, which were divided equally into six groups. For 28 d, the control group received a normal diet and tap water, the corn oil group received a normal diet and 0.5 mL of corn oil by gastric gavage and the malathion group received a normal diet and malathion (100 mg/kg/d) by gastric gavage. During the same period, each of the three other groups received a different dosage of B (5, 10 and 20 mg/kg/d, respectively) and malathion (100 mg/kg/d) by gastric gavage. Malathion administration during the period increased malondialdehyde, nitric oxide and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, as well as markers of liver function, yet decreased acetylcholinesterase, reduced glutathione, superoxide dismutase, and catalase activities in blood, liver, kidney and brain tissues. Administration of B in a dose-dependent manner also reversed malathion-induced oxidative stress, lipid peroxidation (LPO) and antioxidant enzyme activity. Moreover, B exhibited protective action against malathion-induced histopathological changes in liver, kidney and brain tissues. These results demonstrate that, if used in a dose-dependent manner, B decreases malathion-induced oxidative stress, enhances the antioxidant defense mechanism and regenerates tissues in rats.

Protective effect of sulforaphane against oxidative stress: recent advances.

PubMed

Guerrero-Beltrán, Carlos Enrique; Calderón-Oliver, Mariel; Pedraza-Chaverri, José; Chirino, Yolanda Irasema

2012-07-01

Sulforaphane [1-isothiocyanate-(4R)-(methylsulfinyl)butane] is a natural dietary isothiocyanate produced by the enzymatic action of the myrosinase on glucopharanin, a 4-methylsulfinylbutyl glucosinolate contained in cruciferous vegetables of the genus Brassica such as broccoli, brussel sprouts, and cabbage. Studies on this compound is increasing because its anticarcinogenic and cytoprotective properties in several in vivo experimental paradigms associated with oxidative stress such as focal cerebral ischemia, brain inflammation, intracerebral hemorrhage, ischemia and reperfusion induced acute renal failure, cisplatin induced-nephrotoxicity, streptozotocin-induced diabetes, carbon tetrachloride-induced hepatotoxicity and cardiac ischemia and reperfusion. This protective effect also has been observed in in vitro studies in different cell lines such as human neuroblastoma SH-SY5Y, renal epithelial proximal tubule LLC-PK1 cells and aortic smooth muscle A10 cells. Sulforaphane is considered an indirect antioxidant; this compound is able to induce many cytoprotective proteins, including antioxidant enzymes, through the Nrf2-antioxidant response element pathway. Heme oxygenase-1, NAD(P)H: quinone oxidoreductase, glutathione-S-transferase, gamma-glutamyl cysteine ligase, and glutathione reductase are among the cytoprotective proteins induced by sulforaphane. In conclusion, sulforaphane is a promising antioxidant agent that is effective to attenuate oxidative stress and tissue/cell damage in different in vivo and in vitro experimental paradigms. Copyright © 2010 Elsevier GmbH. All rights reserved.

Modifiers of radiation effects in the eye

NASA Astrophysics Data System (ADS)

Kleiman, Norman J.; Stewart, Fiona A.; Hall, Eric J.

2017-11-01

World events, including the threat of radiological terrorism and the fear of nuclear accidents, have highlighted an urgent need to develop medical countermeasures to prevent or reduce radiation injury. Similarly, plans for manned spaceflight to a near-Earth asteroid or journey to Mars raise serious concerns about long-term effects of space radiation on human health and the availability of suitable therapeutic interventions. At the same time, the need to protect normal tissue from the deleterious effects of radiotherapy has driven considerable research into the design of effective radioprotectors. For more than 70 years, animal models of radiation cataract have been utilized to test the short and long-term efficacy of various radiation countermeasures. While some compounds, most notably the Walter Reed (WR) class of radioprotectors, have reported limited effectiveness when given before exposure to low-LET radiation, the human toxicity of these molecules at effective doses limits their usefulness. Furthermore, while there has been considerable testing of eye responses to X- and gamma irradiation, there is limited information about using such models to limit the injurious effects of heavy ions and neutrons on eye tissue. A new class of radioprotector molecules, including the sulfhydryl compound PrC-210, are reported to be effective at much lower doses and with far less side effects. Their ability to modify ocular radiation damage has not yet been examined. The ability to non-invasively measure sensitive, radiation-induced ocular changes over long periods of time makes eye models an attractive option to test the radioprotective and radiation mitigating abilities of new novel compounds.

Oleuropein and hydroxytyrosol protect rats' pups against bisphenol A induced hypothyroidism.

PubMed

Mahmoudi, Asma; Ghorbel, Hèla; Feki, Ines; Bouallagui, Zouhaier; Guermazi, Fadhel; Ayadi, Lobna; Sayadi, Sami

2018-04-27

Bisphenol A (BPA) can disturb the endocrine system and the organs that respond to endocrine signals in organisms, indirectly exposed during prenatal and/or early postnatal life. The present study was designed to assess the protective effect of phenolic compounds from olive leaves against BPA induced thyroid dysfunction and growth perturbation in young rats during lactation. The BPA disrupting effect on thyroid function was investigated by measuring changes in plasma levels of thyroid hormones. Free triiodothyronine (FT3) and thyroxine (FT4) were decreased in young rats breast-fed from mothers treated with bisphenol A. This effect was associated with an increase in the plasma level of thyroid-stimulating hormone (TSH). The histological and immunohistochemical study of the thyroid gland revealed a disturbance in morphological structure and thyroid cells function. Thyroid dysfunction led to a disruption in the skeletal bone growth of young rats. In fact, the infrared microspectroscopic analysis and histological examination of femoral bone showed significant changes in their histoarchitecture associated with a perturbation in the mechanism of bone tissue mineralization. The administration of oleuropein or hydroxytyrosol in BPA treated lactating mothers improved the thyroid cells function by enhancing thyroid hormone levels. Moreover, these phenolics increased the body growth characterized by an amelioration in the structure and the microstructure of femoral bone tissue. HPLC analysis of rats-breast milk indicated the presence of oleuropein and hydroxytyrosol, which could contribute to the protective effect against bisphenol A induced hypothyroidism in pups rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Key Learnings from the Endocrine Disruptor Screening Program (EDSP) Tier 1 Rodent Uterotrophic and Hershberger Assays

PubMed Central

Marty, M Sue; O'Connor, John C

2014-01-01

In 2009, companies began screening compounds using the US Environmental Protection Agency's Endocrine Disruptor Screening Program (EDSP). EDSP has two tiers: Tier 1 includes 11 assays to identify compounds with potential endocrine activity. This article describes two laboratories' experiences conducting Tier 1 uterotrophic and Hershberger assays. The uterotrophic assay detects estrogen receptor agonists through increases in uterine weight. The advantages of the uterotrophic rat models (immature vs. adult ovariectomized) and exposure routes are discussed. Across 29 studies, relative differences in uterine weights in the vehicle control group and 17α-ethynylestradiol–positive control group were reasonably reproducible. The Hershberger assay detects androgen receptor (AR) agonists, antagonists, and 5α-reductase inhibitors through changes in accessory sex tissue (AST) weights. Across 23 studies, AST weights were relatively reproducible for the vehicle groups (baseline), testosterone propionate (TP) groups (androgenic response), and flutamide + TP groups (antiandrogenic response). In one laboratory, one and four compounds were positive in the androgenic and antiandrogenic portions of the assay, respectively. Each compound was also positive for AR binding. In the other laboratory, three compounds showed potential antiandrogenic activity, but each compound was negative for AR binding and did not fit the profile for 5α-reductase inhibition. These compounds induced hepatic enzymes that enhanced testosterone metabolism/clearance, resulting in lower testosterone and decreased capacity to maintain AST weights. The Hershberger androgenic and antiandrogenic performance criteria were generally attainable. Overall, the uterotrophic and Hershberger assays were easily adopted and function as described for EDSP screening, although the mode of action for positive results may not be easily determined. PMID:24515841

Summary of information on synthetic organic compounds and trace elements in tissue of aquatic biota, Clark Fork-Pend Oreille and Spokane River basins, Montana, Idaho, and Washington, 1974-96

USGS Publications Warehouse

Maret, Terry R.; Dutton, DeAnn M.

1999-01-01

As part of the Northern Rockies Intermontane Basins study of the National Water-Quality Assessment Program, data collected between 1974 and 1996 were compiled to describe contaminants in tissue of riverine species. Tissue-contaminant data from 11 monitoring programs and studies representing 28 sites in the study area were summarized. Tissue-contaminant data for most streams generally were lacking. Many studies have focused on and around mining-affected areas on the Clark Fork and Coeur d'Alene Rivers and their major tributaries. DDT and PCBs and their metabolites and congeners were the synthetic organic contaminants most commonly detected in fish tissue. Fish collected from the Spokane River in Washington contained elevated concentrations of PCB arochlors, some of which exceeded guidelines for the protection of human health and predatory wildlife. Tissue samples of fish from the Flathead River watershed contained higher-than-expected concentrations of PCBs, which might have resulted from atmospheric transport. Trace element concentrations in fish and macroinvertebrates collected in and around mining areas were elevated compared with background concentrations. Some cadmium, copper, lead, and mercury concentrations in fish tissue were elevated compared with results from other studies, and some exceeded guidelines. Macroinvertebrates from the Coeur d'Alene River contained higher concentrations of cadmium, lead, and zinc than did macroinvertebrates from other river systems in mining-affected areas. A few sportfish fillet samples, most from the Spokane River in Washington, were collected to assess human health risk. Concentrations of PCBs in these fillets exceeded screening values for the protection of human health. At present, there is no coordinated, long-term fish tissue monitoring program for rivers in the study area, even though contaminants are present in fish at levels considered a threat to human health. Development of a coordinated, centralized national data base for contaminants in fish tissue is needed. The National Water-Quality Assessment Program can provide a framework for other agencies to evaluate tissue contaminants in the Northern Rockies Intermontane Basins study area. As of 1996, there are no fish consumption advisories or fishing restrictions as a result of elevated contaminants on any rivers within the study area.

Can Stress-Induced Biochemical Differences drive Variation in the Hydrogen Isotope Composition of Leaf Wax n-Alkanes from Terrestrial Higher Plants?

NASA Astrophysics Data System (ADS)

Eley, Y.; Pedentchouk, N.; Dawson, L.

2014-12-01

Recent research has identified that interspecies variation in leaf wax n-alkane 2H/1H from plants growing at the same geographical location can exceed 100‰. These differences cannot easily be explained by mechanisms that influence the isotopic composition of leaf water. Biochemical processes are therefore likely to drive some of this variability. Currently, however, little is known about the relative importance of different biochemical processes in shaping n-alkane hydrogen isotope composition. To explore this issue, we combined n-alkane δ2H analysis with measurements of: (i) the percentage content of leaf C and N; and (ii) foliar δ15N, from seven plants growing at Stiffkey salt marsh, Norfolk, UK. These species differ biochemically in respect of the protective compounds they produce under salt or water stressed conditions, with monocots generally producing more carbohydrates, and dicots producing more nitrogenous compounds. We found that monocots had higher %C, while dicots had higher %N and 15N-enriched leaf tissue. We identified a systematic relationship between the nature of the dominant protective compound produced (carbohydrate vs. nitrogenous) and n-alkane 2H/1H: species with a greater proportion of carbohydrates have more negative δ2H values. These findings might imply that shifts in the relative contribution of H to pyruvate from NADPH (2H-depleted) and recycled carbohydrates (2H-enriched) can influence n-alkane δ2H. The 2H-depletion of monocot n-alkanes relative to dicots may therefore be due to a greater proportion of NADPH-derived H incorporated into pyruvate because of their enhanced demand for carbohydrates. The production of protective compounds in plant species is a common response to a range of abiotic stresses (e.g. high UV irradiation, drought, salinity, high/low temperature). Species-specific biochemical responses to stress could therefore influence n-alkane 2H/1H across a range of habitats. This study highlights the importance of detailed investigation of interrelated metabolic networks in a range of plants, to further constrain the isotope effects associated with the cycling of H in plant secondary compounds. Such research will be critical to further develop quantitative interpretations of leaf wax biomarker δ2H records in both modern and ancient contexts.

Protective effect of 4-coumaric acid from UVB ray damage in the rabbit eye.

PubMed

Lodovici, Maura; Caldini, Silvia; Morbidelli, Lucia; Akpan, Victor; Ziche, Marina; Dolara, Piero

2009-01-08

UV-induced oxidation damage seems to play a major role in a number of specific pathological conditions of intraocular tissues, such as cataract formation and retinal degeneration. Therefore, antioxidant and/or scavenger compounds might protect the eyes from UV-induced cellular damage. We previously reported that 4-coumaric acid (4-CA) is able to protect rabbit corneal-derived cells (SIRC) from UVB-induced oxidation damage. In this study we evaluated the protective effect of 4-CA against UVB-induced cell damage in rabbit cornea in vivo. Twelve male New Zealand albino rabbits were used; four rabbits were used as a control and received vehicle in one eye and 4-CA acid in the contralateral eye; eight rabbits were exposed to UVB rays (79.2mJ/cm(2)) and three days before to UV exposure each animal received 1 drop/day of vehicle in one eye and 1 drop/day of vehicle containing 4-CA (164ng) in the contralateral eye. Corneal and sclera tissues were removed and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) levels were measured. Superoxide dismutase (SOD) and xanthine oxidase (XO) activities were determined in aqueous humour. UVB-induced vessel hyper-reactivity was strongly reduced at 4 and 24h after UVB exposure after local treatment with 4-CA, 8-oxodGuo levels, a marker of oxidative DNA damage, were significantly increased (P<0.05) in sclera and cornea by UVB irradiation, but when 4-CA was administered to the conjunctiva in a buffered solution once a day for 3d before and 6d after UVB exposure, levels of 8-oxodGuo were similar to controls and significantly reduced (P<0.05) compared to UVB-treated corneas. XO activity in the aqueous humour was significantly increased. The administration of 4-CA for 3d before and 6d after UVB irradiation induced a small but significant (P<0.05) reduction of XO compared with control eyes. Our results indicate that the administration of 4-CA protects eye tissues, thus reducing the harmful effect of UVB radiation at low concentration, probably through its free radical scavenging and antioxidant properties. Therefore, 4-CA may be useful in protecting the eye from free radical damage following UVB exposure from sunlight, UV lamps and welding torches.

Organochlorine compounds and trace elements in fish tissue and ancillary data for the Connecticut, Housatonic, and Thames river basins study unit, 1992-94

USGS Publications Warehouse

Coles, J.F.

1996-01-01

Concentrations of organochlorine compounds and trace elements were assayed in fish tissue collected from the Connecticut, Housatonic, and Thames River Basins Study Unit, 1992-94. These data were collected to determine the occurrence and distribution of organochlorine compounds and trace elements in the study unit. Ancillary data included are land-use categories by percentage of the sampling-site basins and the size, gender, and age of the individual fish collected for this study. Concentrations of 28 organochlorine compounds in composited whole fish samples were measured at 32 sites, and concentrations of 22 trace elements in composited fish liver samples were measured at 14 of the 32 sites. Most frequently detected organochlorines were DDT related compounds at 31 sites, total PCBs at 28 sites, and chlordane related compounds at 25 sites. Concentrations of total PCBs in fish tissue were generally higher at the large river sites than at the smaller tributary sites. Concentrations of chlordane-related compounds in fish tissue were higher at sites from more urbanized basins than at sites from predominately agriculture and forested basins. Concentrations of the DDT related compounds were undifferentiated among sites comprising different land uses. Trace elements detected at all 14 sites included boron, copper, iron, manganese, molybdenum, selenium, and zinc. Trace elements detected at 10 or more sites included arsenic, mercury, silver, strontium, and vanadium. Antimony, beryllium, and uranium were not detected at any site.

40 CFR 60.622 - Standards for volatile organic compounds.

Code of Federal Regulations, 2010 CFR

2010-07-01

... compounds. 60.622 Section 60.622 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Petroleum Dry Cleaners § 60.622 Standards for volatile organic compounds. (a) Each affected petroleum solvent dry cleaning dryer that is installed at a petroleum dry cleaning plant after December 14, 1982...

40 CFR 60.622 - Standards for volatile organic compounds.

Code of Federal Regulations, 2011 CFR

2011-07-01

... compounds. 60.622 Section 60.622 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Petroleum Dry Cleaners § 60.622 Standards for volatile organic compounds. (a) Each affected petroleum solvent dry cleaning dryer that is installed at a petroleum dry cleaning plant after December 14, 1982...

40 CFR 60.622 - Standards for volatile organic compounds.

Code of Federal Regulations, 2012 CFR

2012-07-01

... compounds. 60.622 Section 60.622 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Petroleum Dry Cleaners § 60.622 Standards for volatile organic compounds. (a) Each affected petroleum solvent dry cleaning dryer that is installed at a petroleum dry cleaning plant after December 14, 1982...

Proteome changes in the skin of the grape cultivar Barbera among different stages of ripening

PubMed Central

Negri, Alfredo S; Prinsi, Bhakti; Rossoni, Mara; Failla, Osvaldo; Scienza, Attilio; Cocucci, Maurizio; Espen, Luca

2008-01-01

Background Grape ripening represents the third phase of the double sigmoidal curve of berry development and is characterized by deep changes in the organoleptic characteristics. In this process, the skin plays a central role in the synthesis of many compounds of interest (e.g. anthocyanins and aroma volatiles) and represents a fundamental protective barrier against damage by physical injuries and pathogen attacks. In order to improve the knowledge on the role of this tissue during ripening, changes in the protein expression in the skin of the red cultivar Barbera at five different stages from véraison to full maturation were studied by performing a comparative 2-DE analysis. Results The proteomic analysis revealed that 80 spots were differentially expressed throughout berry ripening. Applying a two-way hierarchical clustering analysis to these variations, a clear difference between the first two samplings (up to 14 days after véraison) and the following three (from 28 to 49 days after véraison) emerged, thus suggesting that the most relevant changes in protein expression occurred in the first weeks of ripening. By means of LC-ESI-MS/MS analysis, 69 proteins were characterized. Many of these variations were related to proteins involved in responses to stress (38%), glycolysis and gluconeogenesis (13%), C-compounds and carbohydrate metabolism (13%) and amino acid metabolism (10%). Conclusion These results give new insights to the skin proteome evolution during ripening, thus underlining some interesting traits of this tissue. In this view, we observed the ripening-related induction of many enzymes involved in primary metabolism, including those of the last five steps of the glycolytic pathway, which had been described as down-regulated in previous studies performed on whole fruit. Moreover, these data emphasize the relevance of this tissue as a physical barrier exerting an important part in berry protection. In fact, the level of many proteins involved in (a)biotic stress responses remarkably changed through the five stages taken into consideration, thus suggesting that their expression may be developmentally regulated. PMID:18691399

Material design of negative-tone polyphenol resist for EUV and EB lithography

NASA Astrophysics Data System (ADS)

Kojima, Kyoko; Mori, Shigeki; Shiono, Daiju; Hada, Hideo; Onodera, Junichi

2007-03-01

In order to enable design of a negative-tone polyphenol resist using polarity-change reaction, five resist compounds (3M6C-MBSA-BLs) with different number of functional group of γ-hydroxycarboxyl acid were prepared and evaluated by EB lithography. The resist using mono-protected compound (3M6C-MBSA-BL1a) showed 40-nm hp resolution at an improved dose of 52 μC/cm2 probably due to removal of a non-protected polyphenol while the sensitivity of the resist using a compound of protected ratio of 1.1 on average with distribution of different protected ratio was 72 μC/cm2. For evaluation of the di-protected compound based resist, a di-protected polyphenol was synthesized by a newly developed synthetic route of 3-steps reaction, which is well-suited for mass production. The resist using di-protected compound (3M6C-MBSA-BL2b) also showed 40-nm hp resolution at a dose of 40 μC/cm2, which was faster than that of mono-protected resist. Fundamental EUV lithographic evaluation of the resist using 3M6C-MBSA-BL2b by an EUV open frame exposure tool (EUVES-7000) gave its estimated optimum sensitivity of 7 mJ/cm2 and a proof of fine development behavior without any swelling.

Design, synthesis, and evaluation of bioactive molecules; Quantification of tricyclic pyrones from pharmacokinetic studies; Nanodelivery of siRNA; and Synthesis of viral protease inhibitors

NASA Astrophysics Data System (ADS)

Weerasekara, Sahani Manjitha

Four research projects were carried out and they are described in this dissertation. Glycogen synthase kinase-3 beta (GSK3?) plays a pivotal and central role in the pathogenesis of Alzheimer's disease (AD) and protein kinase C (PKC) controls the function of other proteins via phosphorylation and involves in tumor promotion. In pursuit of identifying novel GSK3beta and/or PKC inhibitors, substituted quinoline molecules were designed and synthesized based on the structure-activity-relationship studies. Synthesized molecules were evaluated for their neural protective activities and selected molecules were further tested for inhibitory activities on GSK3beta and PKC enzymes. Among these compounds, compound 2 was found to have better GSK3beta enzyme inhibitory and MC65 cell protection activities at low nanomolar concentrations and poor PKC inhibitory activity whereas compound 3 shows better PKC inhibitory activity. This demonstrates the potential for uses of quinoline scaffold in designing novel compounds for AD and cancer. Pharmacokinetics and distribution profiles of two anti-Alzheimer molecules, CP2 and TP70, discovered in our laboratory were assessed using HPLC/MS. Plasma samples of mice and rats fed with TP70 via different routes over various times were analyzed to quantify the amounts of TP70 in plasma of both species. Distribution profiles of TP70 in various tissues of mice were studied and results show that TP70 penetrated the blood brain barrier and accumulated in the brain tissue in significant amounts. Similarly, the amount of CP2 in plasma of mice was analyzed. The HPLC analysis revealed that both compounds have good PK profiles and bioavailability, which would make them suitable candidates for further in vivo efficacy studies. Nanodelivery of specific dsRNA for suppressing the western corn rootworm (WCR, Diabrotica virgifera virgifera) genes was studied using modified chitosan or modified polyvinylpyrrolidinone (PVP) as nanocarriers. Computational simulation studies of dsRNA with these polymers revealed that nanoparticles can be formed between dsRNA and modified chitosan and PVP polymers. Nanocarriers of hydroxylated PVP (HO-PVP) and chitosan conjugated with polyethylene glycol (PEG) were synthesized, and analyzed using IR spectroscopy. Particle sizes and morphology were evaluated using AFM and encapsulation was studied using UV spectroscopy. However, the formation of stable nanoparticles with dsRNA could not be achieved with either of the polymers, and further efforts are ongoing to discover a better nanocarrier for nanodelivery of siRNA by using chitosan-galactose nanocarrier. In our efforts to discover a novel class of tripeptidyl anti-norovirus compounds that can strongly inhibit NV3CLpro, a set of tripeptidyl molecules were synthesized by modifying the P1 - P3 of the substrate peptide including a warhead. It was found that the replacement of P1 glutamine surrogate with triazole functionality does not improve the inhibitory activities of the compounds. In addition, the synthesis of a known dipeptidyl compound (GC376) was carried out for evaluating its efficacy on feline infectious peritonitis (FIP) in cats.

Use of diphosphonates to correct disorders in calcium metabolism and mineral composition of bone tissue with 60-day hypokinesia in rats

NASA Technical Reports Server (NTRS)

Morukov, B. V.; Zaychik, V. YE.; Ivanov, V. M.; Orlov, O. I.

1988-01-01

Compounds of the diphosphonate group suppress bone resorption and bone tissue metabolism, from which it was assumed that they can be used for the prevention of osteoporosis and disorders of calcium homeostasis in humans during space flight. Two compounds of this group were used for preventive purposes in 60 day hypokinesia in rats. The results showed that diphosphonates have a marked effect on calcium metabolism and the condition of the bone tissues under conditions of long term hypokinesia: they reduce the content of ionized calcium in blood, delay the loss of calcium and phosphorus by the bone tissue, and to a considerable degree prevent reduction of bone density. This confirms the possibility of using compounds of this group for correcting and preventing changes of bone tissue and mineral metabolism during long term hypokinesia.

Precursors to radiopharmaceutical agents for tissue imaging

DOEpatents

Srivastava, Prem C.; Knapp, Jr., Furn F.

1988-01-01

A class of radiolabeled compounds to be used in tissue imaging that exhibits rapid brain uptake, good brain:blood radioactivity ratios, and long retention times. The imaging agents are more specifically radioiodinated aromatic amines attached to dihydropyridine carriers, that exhibit heart as well as brain specificity. In addition to the radiolabeled compounds, classes of compounds are also described that are used as precursors and intermediates in the preparation of the imaging agents.

Identification of a novel selenium-containing compound, selenoneine, as the predominant chemical form of organic selenium in the blood of bluefin tuna.

PubMed

Yamashita, Yumiko; Yamashita, Michiaki

2010-06-11

A novel selenium-containing compound having a selenium atom in the imidazole ring, 2-selenyl-N(alpha),N(alpha),N(alpha)-trimethyl-L-histidine, 3-(2-hydroseleno-1H-imidazol-5-yl)-2-(trimethylammonio)propanoate, was identified from the blood and other tissues of the bluefin tuna, Thunnus orientalis. The selenium-containing compound was purified from the tuna blood in several chromatographic steps. High resolution mass spectrometry and nuclear magnetic resonance spectroscopy showed that the exact mass of the [M+H](+) ion of the compound was 533.0562 and the molecular formula was C(18)H(29)N(6)O(4)Se(2). Its gross structure was assigned as the oxidized dimeric form of an ergothioneine selenium analog in which the sulfur of ergothioneine is replaced by selenium. Therefore, we named this novel selenium-containing compound "selenoneine." By speciation analysis of organic selenium compounds using liquid chromatography inductively coupled plasma mass spectrometry, selenoneine was found widely distributed in various tissues of the tuna, with the highest concentration in blood; mackerel blood contained similar levels. Selenoneine was measurable at 2-4 orders of magnitude lower concentration in a limited set of tissues from squid, tilapia, pig, and chicken. Quantitatively, selenoneine is the predominant form of organic selenium in tuna tissues.

Chlorogenic acid protects mice against lipopolysaccharide-induced acute lung injury.

PubMed

Zhang, Xu; Huang, Huang; Yang, Tingting; Ye, Yin; Shan, Jianhua; Yin, Zhimin; Luo, Lan

2010-07-01

Chlorogenic acid (CGA) is one of the most abundant polyphenol compounds in human diet. Our previous in vitro study demonstrates that CGA presents anti-inflammatory activities in RAW 264.7 cells. Here we show that CGA protects mice against lipopolysaccharide (LPS)-induced acute lung injury (ALI). We treated mice with CGA (5, 20 and 50 mg/kg body weight) 30 min or 3 h after intratracheal administration of LPS. The histological results showed that CGA, at dose of 50 mg/kg, protected mice from LPS-induced ALI which displayed by edema, haemorrhage, blood vessel and alveolar structural damage. CGA inhibited LPS-increased pulmonary MPO activity and migration of polymorphonuclear neutrophils (PMNs) into bronchoalveolar lavage fluid (BALF). Furthermore, CGA markedly decreased the activity of inducible nitric oxide synthase (iNOS) in lung tissues and thus prevented nitric oxide (NO) release in response to LPS challenge. In conclusion, these results indicated that CGA was greatly effective in inhibiting ALI and might act as a potential therapeutic reagent for treating ALI in the future. 2010 Elsevier Ltd. All rights reserved.

A Whole-Body Physiologically Based Pharmacokinetic Model for Colistin and Colistin methanesulfonate (CMS) in Rat.

PubMed

Bouchene, Salim; Marchand, Sandrine; Couet, William; Friberg, Lena E; Gobin, Patrice; Lamarche, Isabelle; Grégoire, Nicolas; Björkman, Sven; Karlsson, Mats O

2018-04-17

Colistin is a polymyxin antibiotic used to treat patients infected with multidrug-resistant Gram negative bacteria (MDR-GNB). The objective of this work was to develop a whole-body physiologically based pharmacokinetic (WB-PBPK) model to predict tissue distribution of colistin in rat. The distribution of a drug in a tissue is commonly characterized by its tissue-to-plasma partition coefficient, K p . Colistin and its prodrug, colistin methanesulfonate (CMS) K p priors were measured experimentally from rat tissue homogenates or predicted in silico. The PK parameters of both compounds were estimated fitting in vivo their plasma concentration-time profiles from six rats receiving an i.v. bolus of CMS. The variability in the data was quantified by applying a non-linear mixed effect (NLME) modelling approach. A WB-PBPK model was developed assuming a well-stirred and perfusion-limited distribution in tissue compartments. Prior information on tissue distribution of colistin and CMS was investigated following three scenarios: K p were estimated using in silico K p priors (I) or K p were estimated using experimental K p priors (II) or K p were fixed to the experimental values (III). The WB-PBPK model best described colistun and CMS plasma concentration-time profiles in scenario II. Colistin predicted concentrations in kidneys in scenario II were higher than in other tissues, which was consistent with its large experimental K p prior. This might be explained by a high affinity of colistin for renal parenchyma and active reabsorption into the proximal tubular cells. In contrast, renal accumulation of colistin was not predicted in scenario I. Colistin and CMS clearance estimates were in agreement with published values. The developed model suggests using experimental priors over in silico K p priors for kidneys to provide a better prediction of colistin renal distribution. Such models might serve in drug development for interspecies scaling and investigating the impact of disease state on colistin disposition. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Heme compounds in dinosaur trabecular bone.

PubMed

Schweitzer, M H; Marshall, M; Carron, K; Bohle, D S; Busse, S C; Arnold, E V; Barnard, D; Horner, J R; Starkey, J R

1997-06-10

Six independent lines of evidence point to the existence of heme-containing compounds and/or hemoglobin breakdown products in extracts of trabecular tissues of the large theropod dinosaur Tyrannosaurus rex. These include signatures from nuclear magnetic resonance and electron spin resonance that indicate the presence of a paramagnetic compound consistent with heme. In addition, UV/visible spectroscopy and high performance liquid chromatography data are consistent with the Soret absorbance characteristic of this molecule. Resonance Raman profiles are also consistent with a modified heme structure. Finally, when dinosaurian tissues were extracted for protein fragments and were used to immunize rats, the resulting antisera reacted positively with purified avian and mammalian hemoglobins. The most parsimonious explanation of this evidence is the presence of blood-derived hemoglobin compounds preserved in the dinosaurian tissues.

Mapping the genetic and tissular diversity of 64 phenolic compounds in Citrus species using a UPLC–MS approach

PubMed Central

Durand-Hulak, Marie; Dugrand, Audray; Duval, Thibault; Bidel, Luc P. R.; Jay-Allemand, Christian; Froelicher, Yann; Bourgaud, Frédéric; Fanciullino, Anne-Laure

2015-01-01

Background and Aims Phenolic compounds contribute to food quality and have potential health benefits. Consequently, they are an important target of selection for Citrus species. Numerous studies on this subject have revealed new molecules, potential biosynthetic pathways and linkage between species. Although polyphenol profiles are correlated with gene expression, which is responsive to developmental and environmental cues, these factors are not monitored in most studies. A better understanding of the biosynthetic pathway and its regulation requires more information about environmental conditions, tissue specificity and connections between competing sub-pathways. This study proposes a rapid method, from sampling to analysis, that allows the quantitation of multiclass phenolic compounds across contrasting tissues and cultivars. Methods Leaves and fruits of 11 cultivated citrus of commercial interest were collected from adult trees grown in an experimental orchard. Sixty-four phenolic compounds were simultaneously quantified by ultra-high-performance liquid chromatography coupled with mass spectrometry. Key Results Combining data from vegetative tissues with data from fruit tissues improved cultivar classification based on polyphenols. The analysis of metabolite distribution highlighted the massive accumulation of specific phenolic compounds in leaves and the external part of the fruit pericarp, which reflects their involvement in plant defence. The overview of the biosynthetic pathway obtained confirmed some regulatory steps, for example those catalysed by rhamnosyltransferases. The results suggest that three other steps are responsible for the different metabolite profiles in ‘Clementine’ and ‘Star Ruby’ grapefruit. Conclusions The method described provides a high-throughput method to study the distribution of phenolic compounds across contrasting tissues and cultivars in Citrus, and offers the opportunity to investigate their regulation and physiological roles. The method was validated in four different tissues and allowed the identification and quantitation of 64 phenolic compounds in 20 min, which represents an improvement over existing methods of analysing multiclass polyphenols. PMID:25757470

40 CFR 721.5980 - Dialkyl phosphorodithioate phosphate compounds.

Code of Federal Regulations, 2010 CFR

2010-07-01

... any information on methods for protecting against such risk, into an MSDS as described at § 721.72(c... compounds. 721.5980 Section 721.5980 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... manner or method of manufacture, import, or processing associated with any use of these substances...

ORGANIC COMPOUNDS IN SURFACE SEDIMENTS AND OYSTER TISSUES FROM THE CHESAPEAKE BAY. APPENDICES

EPA Science Inventory

Detailed in the first part of this report is a development and discussion of the methodology used to extract and analyze sediment and oyster tissue samples from Chesapeake Bay for organic compounds. The method includes extraction, fractionation, and subsequent analysis using glas...

A Review of the Tissue Residue Approach for Organic and Organometallic Compounds in Aquatic Organisms

EPA Science Inventory

This paper reviews the tissue residue approach (TRA) for toxicity assessment as it applies to organic chemicals and some organometallic compounds (tin, mercury, and lead). Specific emphasis was placed on evaluating key factors that influence interpretation of critical body resid...

21 CFR 500.82 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... the sponsored compound in the target tissue of the target animal. R m means the concentration of the... means any compound present in edible tissues of the target animal which results from the use of the... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS...

Anatomy and fructan distribution in vegetative organs of Dimerostemma vestitum (Asteraceae) from the campos rupestres.

PubMed

Silva, Taiza M; Vilhalva, Divina A A; Moraes, Moemy G; Figueiredo-Ribeiro, Rita de Cássia L

2015-01-01

Among the compounds stored by plants, several functions are assigned to fructans, such as source of energy and protection against drought and extreme temperatures. In the present study we analyzed the anatomy and distribution of fructans in vegetative organs of Dimerostemma vestitum (Asteraceae), an endemic species from the Brazilian campos rupestres. D. vestitumhas amphistomatic and pubescent leaves, with both glandular and non-glandular trichomes. In the basal aerial stem the medulla has two types of parenchyma, which differ from the apical portion. The xylopodium has mixed anatomical origin. Interestingly, although inulin-type fructans with high degree of polymerization were found in all analyzed organs except the leaves, the highest amount and maximum degree of polymerization were detected in the xylopodium. Inulin sphero-crystals were visualized under polarized light in the medulla and in the vascular tissues mainly in the central region of the xylopodium, which has abundant xylem parenchyma. Secretory structures accumulating several compounds but not inulin were identified within all the vegetative organs. The presence of these compounds, in addition to inulin, might be related to the strategies of plants to survive adverse conditions in a semi-arid region, affected seasonally by water restriction and frequently by fire.

Mechanism and applications of new fluorescent compounds produced by femtosecond laser surgery in biological tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Qu, Jianan Y.; Sun, Qiqi

2017-02-01

The single or multi-photon microscopy based on fluorescent labelling and staining is a sensitive and quantitative method that is widely used in molecular biology and medical research for a variety of experimental, analytical, and quality control applications. However, label-free method is highly desirable in biology and medicine when performing long term live imaging of biological system and obtaining instant tissue examination during surgery procedures. Recently, our group found that femtosecond laser surgery turned a variety of biological tissues and protein samples into highly fluorescent substances. The newly formed fluorescent compounds produced during the laser surgery can be excited via single- and two-photon processes over broad wavelength ranges. We developed a combined confocal and two-photon spectroscopic microscope to characterize the fluorescence from the new compound systematically. The structures of the femtosecond laser treated tissue were studied using Raman spectroscopy and transmission electron microscopy. Our study revealed the mechanisms of the fluorescence emission form the new compound. Furthermore, we demonstrated the applications of the fluorescent compounds for instant evaluation of femtosecond laser microsurgery, study of stem cell responses to muscle injury and neuro-regeneration after spinal cord injury.

The compound Chinese medicine "Kang Fu Ling" protects against high power microwave-induced myocardial injury.

PubMed

Zhang, Xueyan; Gao, Yabing; Dong, Ji; Wang, Shuiming; Yao, Binwei; Zhang, Jing; Hu, Shaohua; Xu, Xinping; Zuo, Hongyan; Wang, Lifeng; Zhou, Hongmei; Zhao, Li; Peng, Ruiyun

2014-01-01

The prevention and treatment of Microwave-caused cardiovascular injury remains elusive. This study investigated the cardiovascular protective effects of compound Chinese medicine "Kang Fu Ling" (KFL) against high power microwave (HPM)-induced myocardial injury and the role of the mitochondrial permeability transition pore (mPTP) opening in KFL protection. Male Wistar rats (100) were divided into 5 equal groups: no treatment, radiation only, or radiation followed by treatment with KFL at 0.75, 1.5, or 3 g/kg/day. Electrocardiography was used to Electrophysiological examination. Histological and ultrastructural changes in heart tissue and isolated mitochondria were observed by light microscope and electron microscopy. mPTP opening and mitochondrial membrane potential were detected by confocal laser scanning microscopy and fluorescence analysis. Connexin-43 (Cx-43) and endothelial nitric oxide synthase (eNOS) were detected by immunohistochemistry. The expression of voltage-dependent anion channel (VDAC) was detected by western blotting. At 7 days after radiation, rats without KFL treatment showed a significantly lower heart rate (P<0.01) than untreated controls and a J point shift. Myocyte swelling and rearrangement were evident. Mitochondria exhibited rupture, and decreased fluorescence intensity, suggesting opening of mPTP and a consequent reduction in mitochondrial membrane potential. After treatment with 1.5 g/kg/day KFL for 7 d, the heart rate increased significantly (P<0.01), and the J point shift was reduced flavorfully (P<0.05) compared to untreated, irradiated rats; myocytes and mitochondria were of normal morphology. The fluorescence intensities of dye-treated mitochondria were also increased, suggesting inhibition of mPTP opening and preservation of the mitochondrial membrane potential. The microwave-induced decrease of Cx-43 and VDAC protein expression was significantly reversed. Microwave radiation can cause electrophysiological, histological and ultrastructural changes in the heart. KFL at 1.5 g/kg/day had the greatest protective effect on these cardiovascular events. mPTP plays an important role in the protective effects of KFL against microwave-radiation-induced myocardial injury.

Quantification of low molecular weight compounds by MALDI imaging mass spectrometry - A tutorial review.

PubMed

Rzagalinski, Ignacy; Volmer, Dietrich A

2017-07-01

Matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) permits label-free in situ analysis of chemical compounds directly from the surface of two-dimensional biological tissue slices. It links qualitative molecular information of compounds to their spatial coordinates and distribution within the investigated tissue. MALDI-MSI can also provide the quantitative amounts of target compounds in the tissue, if proper calibration techniques are performed. Obviously, as the target molecules are embedded within the biological tissue environment and analysis must be performed at their precise locations, there is no possibility for extensive sample clean-up routines or chromatographic separations as usually performed with homogenized biological materials; ion suppression phenomena therefore become a critical side effect of MALDI-MSI. Absolute quantification by MALDI-MSI should provide an accurate value of the concentration/amount of the compound of interest in relatively small, well-defined region of interest of the examined tissue, ideally in a single pixel. This goal is extremely challenging and will not only depend on the technical possibilities and limitations of the MSI instrument hardware, but equally on the chosen calibration/standardization strategy. These strategies are the main focus of this article and are discussed and contrasted in detail in this tutorial review. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann. Copyright © 2016 Elsevier B.V. All rights reserved.

Metabolomics of cereals under biotic stress: current knowledge and techniques

PubMed Central

Balmer, Dirk; Flors, Victor; Glauser, Gaetan; Mauch-Mani, Brigitte

2013-01-01

Prone to attacks by pathogens and pests, plants employ intricate chemical defense mechanisms consisting of metabolic adaptations. However, many plant attackers are manipulating the host metabolism to counteract defense responses and to induce favorable nutritional conditions. Advances in analytical chemistry have allowed the generation of extensive metabolic profiles during plant-pathogen and pest interactions. Thereby, metabolic processes were found to be highly specific for given tissues, species, and plant-pathogen/pest interactions. The clusters of identified compounds not only serve as base in the quest of novel defense compounds, but also as markers for the characterization of the plants' defensive state. The latter is especially useful in agronomic applications where meaningful markers are essential for crop protection. Cereals such as maize make use of their metabolic arsenal during both local and systemic defense responses, and the chemical response is highly adapted to specific attackers. Here, we summarize highlights and recent findings of metabolic patterns of cereals under pathogen and pest attack. PMID:23630531

Injectable Reactive Biocomposites For Bone Healing In Critical-Size Rabbit Calvarial Defects

DTIC Science & Technology

2012-03-29

defects (i.e. be conformable), provide temporary protection to the brain until the bone heals, and enhance tissue regeneration with the delivery of...temporary protection to the brain until the bone heals, and enhance tissue regeneration with the delivery of biologics. In this study, we evaluated the...complex defects (i.e. be conformable), harden to provide temporary protection until tissue remodels (i.e. be settable), and enhance tissue regeneration

Oxidative stress protection by newly synthesized nitrogen compounds with pharmacological potential.

PubMed

Silva, João P; Areias, Filipe M; Proença, Fernanda M; Coutinho, Olga P

2006-02-09

In this study we used new nitrogen compounds obtained by organic synthesis whose structure predicted an antioxidant potential and then an eventual development as molecules of pharmacological interest in diseases involving oxidative stress. The compounds, identified as FMA4, FMA5, FMA7 and FMA8 differ in the presence of hydroxyl groups located in the C-3 and/or C-4 position of a phenolic unit, which is possibly responsible for their free radicals' buffering capacity. Data from the DPPH discoloration method confirm the high antiradical efficiency of the compounds. The results obtained with cellular models (L929 and PC12) show that they are not toxic and really protect from membrane lipid peroxidation induced by the ascorbate-iron oxidant pair. The level of protection correlates with the drug's lipophilic profile and is sometimes superior to trolox and equivalent to that observed for alpha-tocopherol. The compounds FMA4 and FMA7 present also a high protection from cell death evaluated in the presence of a staurosporine apoptotic stimulus. That protection results in a significant reduction of caspase-3 activity induced by staurosporine which by its turn seems to result from a protection observed in the membrane receptor pathway (caspase-8) together with a protection observed in the mitochondrial pathway (caspase-9). Taken together the results obtained with the new compounds, with linear chains, open up perspectives for their use as therapeutical agents, namely as antioxidants and protectors of apoptotic pathways. On the other hand the slight pro-oxidant profile obtained with the cyclic structures suggests a different therapeutic potential that is under current investigation.

Phenylalanine Is Required to Promote Specific Developmental Responses and Prevents Cellular Damage in Response to Ultraviolet Light in Soybean (Glycine max) during the Seed-to-Seedling Transition

PubMed Central

Sullivan, Joe H.; Muhammad, DurreShahwar; Warpeha, Katherine M.

2014-01-01

UV-radiation elicits a suite of developmental (photomorphogenic) and protective responses in plants, but responses early post-germination have received little attention, particularly in intensively bred plants of economic importance. We examined germination, hypocotyl elongation, leaf pubescence and subcellular responses of germinating and/or etiolated soybean (Glycine max (L.) Merr.) seedlings in response to treatment with discrete wavelengths of UV-A or UV-B radiation. We demonstrate differential responses of germinating/young soybean seedlings to a range of UV wavelengths that indicate unique signal transduction mechanisms regulate UV-initiated responses. We have investigated how phenylalanine, a key substrate in the phenylpropanoid pathway, may be involved in these responses. Pubescence may be a key location for phenylalanine-derived protective compounds, as UV-B irradiation increased pubescence and accumulation of UV-absorbing compounds within primary leaf pubescence, visualized by microscopy and absorbance spectra. Mass spectrometry analysis of pubescence indicated that sinapic esters accumulate in the UV-irradiated hairs compared to unirradiated primary leaf tissue. Deleterious effects of some UV-B wavelengths on germination and seedling responses were reduced or entirely prevented by inclusion of phenylalanine in the growth media. Key effects of phenylalanine were not duplicated by tyrosine or tryptophan or sucrose, nor is the specificity of response due to the absorbance of phenylalanine itself. These results suggest that in the seed-to-seedling transition, phenylalanine may be a limiting factor in the development of initial mechanisms of UV protection in the developing leaf. PMID:25549094

Utilization of robotic-arm assisted total knee arthroplasty for soft tissue protection.

PubMed

Sultan, Assem A; Piuzzi, Nicolas; Khlopas, Anton; Chughtai, Morad; Sodhi, Nipun; Mont, Michael A

2017-12-01

Despite the well-established success of total knee arthroplasty (TKA), iatrogenic ligamentous and soft tissue injuries are infrequent, but potential complications that can have devastating impact on clinical outcomes. These injuries are often related to technical errors and excessive soft tissue manipulation, particularly during bony resections. Recently, robotic-arm assisted TKA was introduced and demonstrated promising results with potential technical advantages over manual surgery in implant positioning and mechanical accuracy. Furthermore, soft tissue protection is an additional potential advantage offered by these systems that can reduce inadvertent human technical errors encountered during standard manual resections. Therefore, due to the relative paucity of literature, we attempted to answer the following questions: 1) does robotic-arm assisted TKA offer a technical advantage that allows enhanced soft tissue protection? 2) What is the available evidence about soft tissue protection? Recently introduced models of robotic-arm assisted TKA systems with advanced technology showed promising clinical outcomes and soft tissue protection in the short- and mid-term follow-up with results comparable or superior to manual TKA. In this review, we attempted to explore this dimension of robotics in TKA and investigate the soft tissue related complications currently reported in the literature.

Plant-derived phenolic compounds prevent the DNA single-strand breakage and cytotoxicity induced by tert-butylhydroperoxide via an iron-chelating mechanism.

PubMed Central

Sestili, Piero; Diamantini, Giuseppe; Bedini, Annalida; Cerioni, Liana; Tommasini, Ilaria; Tarzia, Giorgio; Cantoni, Orazio

2002-01-01

The protective effects of selected members from a series of caffeic acid esters and flavonoids were tested in various toxicity paradigms using U937 cells, previously shown to be sensitive to either iron chelators or bona fide radical scavengers or to both classes of compounds. It was found that all the protective polyphenols were active at very low concentrations and that their effects were observed only under those conditions in which iron chelators also afforded protection. Consistently, active polyphenolic compounds, unlike the inactive ones, effectively chelated iron in an in vitro system. It follows that, at least under the experimental conditions utilized in the present study, the most prominent activity of these polyphenolic compounds resides in their ability to chelate iron. Further studies revealed that the protective effects afforded by the caffeic acid esters and flavonoids were largely mediated by the catechol moiety and that the relative biological potency of these compounds was a direct function of their lipophilicity. PMID:11988084

Organochlorine compounds and trace elements in fish tissue and streambed sediment in the Mobile River Basin, Alabama, Mississippi, and Georgia, 1998

USGS Publications Warehouse

Zappia, Humbert

2002-01-01

During the summer of 1998, as part of the National Water-Quality Assessment Program, a survey was conducted to determine which organochlorine compounds and trace elements occur in fish tissues and streambed sediments in the Mobile River Basin, which includes parts of Alabama, Mississippi, Georgia, and Tennessee. The data collected were compared to guidelines related to wildlife, land use, and to 1991 and 1994 National Water-Quality Assessment Program Study-Unit data.Twenty-one sites were sampled in subbasins of the Mobile River Basin. The subbasins ranged in size from about 9 to 22,000 square miles and were dominated by either a single land use or a combination of land uses. The major land-use categories were urban, agriculture, and forest.Organochlorine compounds were widespread spatially in the Mobile River Basin. At least one organochlorine compound was reported at the majority of sampling sites (84 percent) and in a majority of whole-fish (80 percent) and streambed-sediment (52 percent) samples. Multiple organochlorine compounds were reported at 75 percent of the sites where fish tissues were collected and were reported at many of the streambed-sediment sampling sites (45 percent). The majority of concentrations reported, however, were less than 5 micrograms per kilogram in fish-tissue samples and less than 1 microgram per kilogram in streambed-sediment samples.The majority of trace elements analyzed in fish-liver tissue (86 percent) and streambed-sediment (98 percent) samples were reported during this study. Multiple trace elements were reported in all samples and at all sites.Based on comparisons of concentrations of organochlorine compounds and trace elements in fish-tissue and streambed-sediment samples in relation to National Academy of Science and National Academy of Engineering and Canadian tissue guidelines, probable-effects concentrations, and mean probable-effects concentration quotients for streambed sediment, the potential exists for adverse effects to wildlife at 15 (72 percent) of the sites sampled. The potential for adverse effects at these sites is because of the presence of residues or breakdown products related to polychlorinated biphenyls (PCB?s), chlordane, dichlorodiphenyltrichloroethane (DDT), chromium, lead, and zinc.The majority of compounds reported (65 percent) were chlordane, DDT, and PCB?s, or their breakdown products. Concentrations of chlordane and heptachlor epoxide in whole-fish tissue were positively correlated to the amount of urban land use in a basin. Total DDT concentrations in whole-fish tissues were positively correlated to agriculture.The relation of trace elements to land use is not as clear as the relation of organochlorine compounds to land use. This lack of clarity may be due to the possibility of geologic sources of trace elements in the Mobile River Basin and to the ubiquitous nature of many of these trace elements. However, there may be a correlation between the amount of urban land use and concentrations of antimony, cadmium, lead, and zinc in streambed-sediment samples from the Mobile River Basin.Fewer organochlorine compounds and trace elements were reported in samples from the Mobile River Basin than in samples collected during the 1991 and 1994 National Water-Quality Assessment Program studies. Of the organochlorine compounds analyzed nationally, 57 percent were reported in whole-fish tissue samples collected locally and 41 percent were reported in streambed-sediment samples collected locally, whereas 96 percent and 86 percent, respectively, were reported nationally. Of trace elements analyzed nationally, 86 percent were reported in fish-liver tissue locally and 95 percent were reported in streambed-sediment samples locally, whereas 95 percent and 98 percent, respectively, were reported nationally.In general, concentrations of organochlorine compounds and trace elements and the frequency with which they were reported in the Mobile River Basin are similar to or less than t

Compounds isolated from Eriobotrya deflexa leaves protect against ultraviolet radiation B-induced photoaging in human fibroblasts.

PubMed

Huang, Chung-Yu; Lin, Yi-Tzu; Kuo, Hsiang-Chun; Chiou, Wen-Fei; Lee, Mei-Hsien

2017-10-01

Ultraviolet (UV) irradiation leads to skin photoaging because of the upregulation of matrix metalloproteinase (MMP)-1 and downregulation of type I collagen and tissue inhibitor of metalloproteinase (TIMP)-1. Eriobotrya deflexa (Hemsl.) Nakai (Rosaceae) is a flowering plant endemic to Taiwan, and its leaves have been used as an expectorant and in antitussive folk remedy. Our previous studies have demonstrated that an E. deflexa leaf extract functions as a free radical scavenger. The current evaluated the antiphotoaging effect of partitioned fractions and specific compounds from the leaves of E. deflexa by using bioguided isolation, compound identification, and biological activity testing with UVB-irradiated human fibroblasts (WS-1 cells). E. deflexa leaves were extracted with 95% ethanol and then partitioned using a sequential treatment of n-hexane, ethyl acetate, and n-butanol (n-BuOH). The bioactive n-BuOH fraction was used for isolation and purification through chromatography. The compounds were identified by analyzing their physical and spectroscopic properties. We identified eight compounds from this fraction; of these compounds, 3-O-α-l-rhamnopyranosyl-(1‴→6″)-β-d-galactopyranoside (1), hyperin (2), afzelin (5), and cryptochlorogenic acid methyl ester (7) were isolated from E. deflexa for the first time, and they exhibited MMP-1 inhibition activity. The IC 50 values were 96.5, 89.5, 93.4, and 92.8μM for 1, 2, 5, and 7, respectively. These compounds also enhanced the expression of procollagen type I, and TIMP-1 and hyperin (2) were found to be most effective with IC 50 values of 56.7 and 70.3μM, respectively. Hyperin (2) could reduce intracellular reactive oxygen species production in UVB-irradiated WS-1 cells, with the corresponding IC 50 value being 80.7μM. Liquid chromatography triple-quadrupole mass spectrometry was used for the quantitative and chemical fingerprint analysis of active compounds. Quercetin 3-O-α-l-rhamnopyranosyl-(1‴→6″)-β-d-galactopyranoside (1), hyperin (2), afzelin (5), and cryptochlorogenic acid methyl ester (7) constituted 24.2±3.9, 5.5±1.0, 3.4±0.3, and 67.1±8.1mg/g of dry weight in the active n-BuOH fraction, respectively. Our results demonstrate that the extract and the isolated active compounds from E. deflexa leaves possess the potential for protection against skin photoaging. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical composition and hepatoprotective activity of ethanolic root extract of Taraxacum Syriacum Boiss against acetaminophen intoxication in rats.

PubMed

Nazari, A; Fanaei, H; Dehpour, A R; Hassanzadeh, G; Jafari, M; Salehi, M; Mohammadi, M

2015-01-01

In the present study, the role of ethanol extract of root of Taraxacum Syriacum Boiss (TSBE) against hepatotoxicity caused by acetaminophen (APAP) was studied. The chemical composition of roots of Taraxacum Syriacum Boiss was analyzed by SPME-GC/MS method. Hepatocellular injuries induced by acetaminophen (APAP) were assessed by liver histology, serum aminotransferase activities, antioxidant enzymes activity and lipid peroxidation in liver tissue. TSBE was observed to exhibit hepatoprotective effect as demonstrated by significant decrease in serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), and alkaline phosphatase (ALP) concentration, and by preventing liver histopathologic changes in rats with APAP hepatotoxicity. Administration of APAP, significantly increased, lactate dehydrogenase (LDH) and catalase (CAT) activity in liver tissue and pretreatment with TSBE returned these parameters to control group, moreover TSBE reduces APAP-induced hepatic Glutathione (GSH) depletion. Carvacrol (6.7 %) was the main polyphenolic compound of plant sample. Our results demonstrated hepatoprotective activity of TSBE in rat in vivo. We believe that the mechanism by which the extract was able to protect the liver from the oxidative stress generated by APAP is due to its antioxidant activity. These phenolic compounds of the extract act as antioxidants and free radical scavengers and reduce or inhibit the oxidative stress induced by APAP administration (Tab. 3, Fig. 3, Ref. 39).

Erythropoietin and engineered innate repair activators.

PubMed

Brines, Michael; Cerami, Anthony

2013-01-01

Erythropoietin (EPO) is a pleiotropic type I cytokine that has been identified as a major endogenous tissue protective molecule. In response to injury, EPO and a distinct receptor are expressed with a characteristic temporal and spatial expression pattern. Together, these serve to limit injury and to initiate repair. Administration of EPO in the setting of injury has been shown to be beneficial in a multitude of preclinical models. However, translation into the clinic has been hampered by EPO's adverse effects, including promotion of thrombosis. Recently, engineered molecules based on EPO's structure-activity relationships have been developed that are devoid of hematopoietic effects. These compounds are promising candidates for treatment of a wide variety of acute and chronic diseases.

Erythropoietin-mediated tissue protection: reducing collateral damage from the primary injury response.

PubMed

Brines, M; Cerami, A

2008-11-01

In its classic hormonal role, erythropoietin (EPO) is produced by the kidney and regulates the number of erythrocytes within the circulation to provide adequate tissue oxygenation. EPO also mediates other effects directed towards optimizing oxygen delivery to tissues, e.g. modulating regional blood flow and reducing blood loss by promoting thrombosis within damaged vessels. Over the past 15 years, many unexpected nonhaematopoietic functions of EPO have been identified. In these more recently appreciated nonhormonal roles, locally-produced EPO signals through a different receptor isoform and is a major molecular component of the injury response, in which it counteracts the effects of pro-inflammatory cytokines. Acutely, EPO prevents programmed cell death and reduces the development of secondary, pro-inflammatory cytokine-induced injury. Within a longer time frame, EPO provides trophic support to enable regeneration and healing. As the region immediately surrounding damage is typically relatively deficient in endogenous EPO, administration of recombinant EPO can provide increased tissue protection. However, effective use of EPO as therapy for tissue injury requires higher doses than for haematopoiesis, potentially triggering serious adverse effects. The identification of a tissue-protective receptor isoform has facilitated the engineering of nonhaematopoietic, tissue-protective EPO derivatives, e.g. carbamyl EPO, that avoid these complications. Recently, regions within the EPO molecule mediating tissue protection have been identified and this has enabled the development of potent tissue-protective peptides, including some mimicking EPO's tertiary structure but unrelated in primary sequence.

Erythropoietin mediates tissue protection through an erythropoietin and common beta-subunit heteroreceptor.

PubMed

Brines, Michael; Grasso, Giovanni; Fiordaliso, Fabio; Sfacteria, Alessandra; Ghezzi, Pietro; Fratelli, Maddalena; Latini, Roberto; Xie, Qiao-Wen; Smart, John; Su-Rick, Chiao-Ju; Pobre, Eileen; Diaz, Deborah; Gomez, Daniel; Hand, Carla; Coleman, Thomas; Cerami, Anthony

2004-10-12

The cytokine erythropoietin (Epo) is tissue-protective in preclinical models of ischemic, traumatic, toxic, and inflammatory injuries. We have recently characterized Epo derivatives that do not bind to the Epo receptor (EpoR) yet are tissue-protective. For example, carbamylated Epo (CEpo) does not stimulate erythropoiesis, yet it prevents tissue injury in a wide variety of in vivo and in vitro models. These observations suggest that another receptor is responsible for the tissue-protective actions of Epo. Notably, prior investigation suggests that EpoR physically interacts with the common beta receptor (betacR), the signal-transducing subunit shared by the granulocyte-macrophage colony stimulating factor, and the IL-3 and IL-5 receptors. However, because betacR knockout mice exhibit normal erythrocyte maturation, betacR is not required for erythropoiesis. We hypothesized that betacR in combination with the EpoR expressed by nonhematopoietic cells constitutes a tissue-protective receptor. In support of this hypothesis, membrane proteins prepared from rat brain, heart, liver, or kidney were greatly enriched in EpoR after passage over either Epo or CEpo columns but covalently bound in a complex with betacR. Further, antibodies against EpoR coimmunoprecipitated betacR from membranes prepared from neuronal-like P-19 cells that respond to Epo-induced tissue protection. Immunocytochemical studies of spinal cord neurons and cardiomyocytes protected by Epo demonstrated cellular colocalization of Epo betacR and EpoR. Finally, as predicted by the hypothesis, neither Epo nor CEpo was active in cardiomyocyte or spinal cord injury models performed in the betacR knockout mouse. These data support the concept that EpoR and betacR comprise a tissue-protective heteroreceptor.

Key learnings from the Endocrine Disruptor Screening Program (EDSP) Tier 1 rodent uterotrophic and Hershberger assays.

PubMed

Marty, M Sue; O'Connor, John C

2014-02-01

In 2009, companies began screening compounds using the US Environmental Protection Agency's Endocrine Disruptor Screening Program (EDSP). EDSP has two tiers: Tier 1 includes 11 assays to identify compounds with potential endocrine activity. This article describes two laboratories' experiences conducting Tier 1 uterotrophic and Hershberger assays. The uterotrophic assay detects estrogen receptor agonists through increases in uterine weight. The advantages of the uterotrophic rat models (immature vs. adult ovariectomized) and exposure routes are discussed. Across 29 studies, relative differences in uterine weights in the vehicle control group and 17α-ethynylestradiol-positive control group were reasonably reproducible. The Hershberger assay detects androgen receptor (AR) agonists, antagonists, and 5α-reductase inhibitors through changes in accessory sex tissue (AST) weights. Across 23 studies, AST weights were relatively reproducible for the vehicle groups (baseline), testosterone propionate (TP) groups (androgenic response), and flutamide + TP groups (antiandrogenic response). In one laboratory, one and four compounds were positive in the androgenic and antiandrogenic portions of the assay, respectively. Each compound was also positive for AR binding. In the other laboratory, three compounds showed potential antiandrogenic activity, but each compound was negative for AR binding and did not fit the profile for 5α-reductase inhibition. These compounds induced hepatic enzymes that enhanced testosterone metabolism/clearance, resulting in lower testosterone and decreased capacity to maintain AST weights. The Hershberger androgenic and antiandrogenic performance criteria were generally attainable. Overall, the uterotrophic and Hershberger assays were easily adopted and function as described for EDSP screening, although the mode of action for positive results may not be easily determined. © 2014 Wiley Periodicals, Inc.

Antiviral activity of a small-molecule inhibitor of filovirus infection.

PubMed

Warren, Travis K; Warfield, Kelly L; Wells, Jay; Enterlein, Sven; Smith, Mark; Ruthel, Gordon; Yunus, Abdul S; Kinch, Michael S; Goldblatt, Michael; Aman, M Javad; Bavari, Sina

2010-05-01

There exists an urgent need to develop licensed drugs and vaccines for the treatment or prevention of filovirus infections. FGI-103 is a low-molecular-weight compound that was discovered through an in vitro screening assay utilizing a variant of Zaire ebolavirus (ZEBOV) that expresses green fluorescent protein. In vitro analyses demonstrated that FGI-103 also exhibits antiviral activity against wild-type ZEBOV and Sudan ebolavirus, as well as Marburgvirus (MARV) strains Ci67 and Ravn. In vivo administration of FGI-103 as a single intraperitoneal dose of 10 mg/kg delivered 24 h after infection is sufficient to completely protect mice against a lethal challenge with a mouse-adapted strain of either ZEBOV or MARV-Ravn. In a murine model of ZEBOV infection, delivery of FGI-103 reduces viremia and the viral burden in kidney, liver, and spleen tissues and is associated with subdued and delayed proinflammatory cytokine responses and tissue pathology. Taken together, these results identify a promising antiviral therapeutic candidate for the treatment of filovirus infections.

Fresh broad (Vicia faba) tissue homogenate-based biosensor for determination of phenolic compounds.

PubMed

Ozcan, Hakki Mevlut; Sagiroglu, Ayten

2014-08-01

In this study, a novel fresh broad (Vicia faba) tissue homogenate-based biosensor for determination of phenolic compounds was developed. The biosensor was constructed by immobilizing tissue homogenate of fresh broad (Vicia faba) on to glassy carbon electrode. For the stability of the biosensor, general immobilization techniques were used to secure the fresh broad tissue homogenate in gelatin-glutaraldehyde cross-linking matrix. In the optimization and characterization studies, the amount of fresh broad tissue homogenate and gelatin, glutaraldehyde percentage, optimum pH, optimum temperature and optimum buffer concentration, thermal stability, interference effects, linear range, storage stability, repeatability and sample applications (Wine, beer, fruit juices) were also investigated. Besides, the detection ranges of thirteen phenolic compounds were obtained with the help of the calibration graphs. A typical calibration curve for the sensor revealed a linear range of 5-60 μM catechol. In reproducibility studies, variation coefficient (CV) and standard deviation (SD) were calculated as 1.59%, 0.64×10(-3) μM, respectively.

The Mitochondria-Targeted Antioxidant Mitoquinone Protects against Cold Storage Injury of Renal Tubular Cells and Rat Kidneys

PubMed Central

Mitchell, Tanecia; Rotaru, Dumitru; Saba, Hamida; Smith, Robin A. J.; Murphy, Michael P.

2011-01-01

The majority of kidneys used for transplantation are obtained from deceased donors. These kidneys must undergo cold preservation/storage before transplantation to preserve tissue quality and allow time for recipient selection and transport. However, cold storage (CS) can result in tissue injury, kidney discardment, or long-term renal dysfunction after transplantation. We have previously determined mitochondrial superoxide and other downstream oxidants to be important signaling molecules that contribute to CS plus rewarming (RW) injury of rat renal proximal tubular cells. Thus, this study's purpose was to determine whether adding mitoquinone (MitoQ), a mitochondria-targeted antioxidant, to University of Wisconsin (UW) preservation solution could offer protection against CS injury. CS was initiated by placing renal cells or isolated rat kidneys in UW solution alone (4 h at 4°C) or UW solution containing MitoQ or its control compound, decyltriphenylphosphonium bromide (DecylTPP) (1 μM in vitro; 100 μM ex vivo). Oxidant production, mitochondrial function, cell viability, and alterations in renal morphology were assessed after CS exposure. CS induced a 2- to 3-fold increase in mitochondrial superoxide generation and tyrosine nitration, partial inactivation of mitochondrial complexes, and a significant increase in cell death and/or renal damage. MitoQ treatment decreased oxidant production ∼2-fold, completely prevented mitochondrial dysfunction, and significantly improved cell viability and/or renal morphology, whereas DecylTPP treatment did not offer any protection. These findings implicate that MitoQ could potentially be of therapeutic use for reducing organ preservation damage and kidney discardment and/or possibly improving renal function after transplantation. PMID:21159749

The mitochondria-targeted antioxidant mitoquinone protects against cold storage injury of renal tubular cells and rat kidneys.

PubMed

Mitchell, Tanecia; Rotaru, Dumitru; Saba, Hamida; Smith, Robin A J; Murphy, Michael P; MacMillan-Crow, Lee Ann

2011-03-01

The majority of kidneys used for transplantation are obtained from deceased donors. These kidneys must undergo cold preservation/storage before transplantation to preserve tissue quality and allow time for recipient selection and transport. However, cold storage (CS) can result in tissue injury, kidney discardment, or long-term renal dysfunction after transplantation. We have previously determined mitochondrial superoxide and other downstream oxidants to be important signaling molecules that contribute to CS plus rewarming (RW) injury of rat renal proximal tubular cells. Thus, this study's purpose was to determine whether adding mitoquinone (MitoQ), a mitochondria-targeted antioxidant, to University of Wisconsin (UW) preservation solution could offer protection against CS injury. CS was initiated by placing renal cells or isolated rat kidneys in UW solution alone (4 h at 4°C) or UW solution containing MitoQ or its control compound, decyltriphenylphosphonium bromide (DecylTPP) (1 μM in vitro; 100 μM ex vivo). Oxidant production, mitochondrial function, cell viability, and alterations in renal morphology were assessed after CS exposure. CS induced a 2- to 3-fold increase in mitochondrial superoxide generation and tyrosine nitration, partial inactivation of mitochondrial complexes, and a significant increase in cell death and/or renal damage. MitoQ treatment decreased oxidant production ~2-fold, completely prevented mitochondrial dysfunction, and significantly improved cell viability and/or renal morphology, whereas DecylTPP treatment did not offer any protection. These findings implicate that MitoQ could potentially be of therapeutic use for reducing organ preservation damage and kidney discardment and/or possibly improving renal function after transplantation.

Recombinant interferon-gamma secreted by Chinese hamster ovary-320 cells cultivated in suspension in protein-free media is protected against extracellular proteolysis by the expression of natural protease inhibitors and by the addition of plant protein hydrolysates to the culture medium.

PubMed

Mols, J; Peeters-Joris, C; Wattiez, R; Agathos, S N; Schneider, Y-J

2005-01-01

Biosafety requirements increasingly restrict the cultivation of mammalian cells producing therapeutic glycoproteins to conditions that are devoid of any compound of animal origin. On cultivation in serum-free media, the proteases inhibitors, usually found in serum, cannot protect secreted recombinant proteins against unwanted endogenous proteolysis. Chinese hamster ovary (CHO) cells, secreting recombinant human interferon-gamma (CHO-320 cell line) and cultivated in suspension in an original protein-free medium, expressed at least two members of the matrix metalloproteinases (MMP), either at the cell surface (proMMP-14 and MMP-14) or secreted (proMMP-9). In addition, tissue- and urinary-type plasminogen activators were also secreted in such culture conditions. At the cell surface, dipeptidyl peptidase IV and tripeptidyl peptidase II (TPPII) activities were also detected, and their activities decreased during time course of batch cultures. The proteolytic activities of these proteins were counterbalanced by (1) their expression as zymogens (proMMP-9, proMMP-14), (2) the expression of their natural inhibitors, tissue inhibitors of metalloproteinases-1 and -2 and plasminogen activator inhibitor-1 (PAI-1), or (3) the addition of plant protein hydrolysates to the culture medium, acting as a nonspecific source of TPPII inhibitors. This study points out that, even in protein-free media, recombinant proteins secreted by CHO cells are actively protected against physiological and unwanted extracellular proteolysis either by endogenous or by exogenous inhibitors.

Discovery of new MD2 inhibitor from chalcone derivatives with anti-inflammatory effects in LPS-induced acute lung injury

PubMed Central

Zhang, Yali; Wu, Jianzhang; Ying, Shilong; Chen, Gaozhi; Wu, Beibei; Xu, Tingting; Liu, Zhiguo; Liu, Xing; Huang, Lehao; Shan, Xiaoou; Dai, Yuanrong; Liang, Guang

2016-01-01

Acute lung injury (ALI) is a life-threatening acute inflammatory disease with limited options available for therapy. Myeloid differentiation protein 2, a co-receptor of TLR4, is absolutely required for TLR4 sense LPS, and represents an attractive target for treating severe inflammatory diseases. In this study, we designed and synthesized 31 chalcone derivatives that contain the moiety of (E)-4-phenylbut-3-en-2-one, which we consider the core structure of current MD2 inhibitors. We first evaluated the anti-inflammatory activities of these compounds in MPMs. For the most active compound 20, we confirmed that it is a specific MD2 inhibitor through a series of biochemical experiments and elucidated that it binds to the hydrophobic pocket of MD2 via hydrogen bonds with Arg90 and Tyr102 residues. Compound 20 also blocked the LPS-induced activation of TLR4/MD2 -downstream pro-inflammatory MAPKs/NF-κB signaling pathways. In a rat model with ALI induced by intracheal LPS instillation, administration with compound 20 exhibited significant protective effect against ALI, accompanied by the inhibition of TLR4/MD2 complex formation in lung tissues. Taken together, the results of this study suggest the specific MD2 inhibitor from chalcone derivatives we identified is a potential candidate for treating acute inflammatory diseases. PMID:27118147

Dietary quebracho tannins are not absorbed, but increase the antioxidant capacity of liver and plasma in sheep.

PubMed

López-Andrés, Patricia; Luciano, Giuseppe; Vasta, Valentina; Gibson, Trevor M; Biondi, Luisa; Priolo, Alessandro; Mueller-Harvey, Irene

2013-08-01

A total of sixteen lambs were divided into two groups and fed two different diets. Of these, eight lambs were fed a control diet (C) and eight lambs were fed the C diet supplemented with quebracho tannins (C+T). The objective of the present study was to assess whether dietary quebracho tannins can improve the antioxidant capacity of lamb liver and plasma and if such improvement is due to a direct transfer of phenolic compounds or their metabolites, to the animal tissues. Feed, liver and plasma samples were purified by solid-phase extraction (SPE) and analysed by liquid chromatography-MS for phenolic compounds. Profisitinidin compounds were identified in the C+T diet. However, no phenolic compounds were found in lamb tissues. The liver and the plasma from lambs fed the C+T diet displayed a greater antioxidant capacity than tissues from lambs fed the C diet, but only when samples were not purified with SPE. Profisetinidin tannins from quebracho seem not to be degraded or absorbed in the gastrointestinal tract. However, they induced antioxidant effects in animal tissues.

Protective effects of a natural herbal compound quercetin against snake venom-induced hepatic and renal toxicities in rats.

PubMed

Al-Asmari, Abdulrahman K; Khan, Haseeb A; Manthiri, Rajamohamed A; Al-Khlaiwi, Ahmad A; Al-Asmari, Bayan A; Ibrahim, Khalid E

2018-05-08

Echis pyramidum is a highly poisonous viper snake. Previous studies have shown acute phase hepatic and renal toxicities of Echis pyramidum venom (EPV) in rats. This study reports the protective effects of a natural herbal compound quercetin (QRC) on EPV-induced hepatic and renal toxicities in rats. A singly injection of EPV (4.76 mg/kg) caused significant increase in serum biomarkers of liver and kidney function. Pre-treatment of QRC (10 mg/kg) significantly reduced the toxic effects of EPV on functional impairment in liver and kidneys of rats. Administration of QRC also reversed EPV-induced increase in lipid peroxidation and decrease in total thiols. The histopathology of liver showed fat accumulation, focal degeneration and cytoplasmic vacuolation of hepatocytes in EPV treated rats. EPV also caused renal tubular dilation and focal atrophy of glomerular tufts in rat kidneys. Administration of QRC prevented EPV-induced structural tissue damage in liver and kidneys of rats. In conclusion, QRC significantly inhibited the acute phase toxic effects of EPV on liver and kidneys of rats by preventing the oxidative stress in these organs. QRC is also known for its anti-inflammatory, anti-edema, anti-hemorrhagic and PLA2-inhibitory properties and therefore may be regarded as a multi-action antidote against snake venom toxicity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Protective effects of Curcuma longa against neurobehavioral and neurochemical damage caused by cerium chloride in mice.

PubMed

Kadri, Yamina; Nciri, Riadh; Brahmi, Noura; Saidi, Saber; Harrath, Abdel Halim; Alwasel, Saleh; Aldahmash, Waleed; El Feki, Abdelfatteh; Allagui, Mohamed Salah

2018-05-07

Cerium chloride (CeCl 3 ) is considered an environmental pollutant and a potent neurotoxic agent. Medicinal plants have many bioactive compounds that provide protection against damage caused by such pollutants. Curcuma longa is a bioactive compound-rich plant with very important antioxidant properties. To study the preventive and healing effects of Curcuma longa on cerium-damaged mouse brains, we intraperitoneally injected cerium chloride (CeCl 3 , 20 mg/kg BW) along with Curcuma longa extract, administrated by gavage (100 mg/kg BW), into mice for 60 days. We then examined mouse behavior, brain tissue damage, and brain oxidative stress parameters. Our results revealed a significant modification in the behavior of the CeCl 3 -treated mice. In addition, CeCl 3 induced a significant increment in lipid peroxidation, carbonyl protein (PCO), and advanced oxidation protein product levels, as well as a significant reduction in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Acetylcholinesterase (AChE) activity remarkably increased in the brain of CeCl 3 -treated mice. Histopathological observations confirmed these results. Curcuma longa attenuated CeCl 3 -induced oxidative stress and increased the activities of antioxidant enzymes. It also decreased AChE activity in the CeCl 3 -damaged mouse brain that was confirmed by histopathology. In conclusion, this study suggests that Curcuma longa has a neuroprotective effect against CeCl 3 -induced damage in the brain.

Antisecretory, Gastroprotective, Antioxidant and Anti-Helicobcter Pylori Activity of Zerumbone from Zingiber Zerumbet (L.) Smith

PubMed Central

Sidahmed, Heyam Mohamed Ali; Hashim, Najihah Mohd; Abdulla, Mahmood Ameen; Ali, Hapipah Mohd; Mohan, Syam; Abdelwahab, Siddig Ibrahim; Taha, Manal Mohamed Elhassan; Fai, Loke Mun; Vadivelu, Jamuna

2015-01-01

Background Zingiber zerumbet Smith is a perennial herb, broadly distributed in many tropical areas. In Malaysia, it’s locally known among the Malay people as “lempoyang” and its rhizomes, particularly, is widely used in traditional medicine for the treatment of peptic ulcer disease beyond other gastric disorders. Aim of the study The aim of the current study is to evaluate the gastroprotective effect of zerumbone, the main bioactive compound of Zingiber zerumbet rhizome, against ethanol-induced gastric ulcer model in rats. Materials and Methods Rats were pre-treated with zerumbone and subsequently exposed to acute gastric ulcer induced by absolute ethanol administration. Following treatment, gastric juice acidity, ulcer index, mucus content, histological analysis (HE and PAS), immunohistochemical localization for HSP-70, prostaglandin E2 synthesis (PGE2), non-protein sulfhydryl gastric content (NP-SH), reduced glutathione level (GSH), and malondialdehyde level (MDA) were evaluated in ethanol-induced ulcer in vivo. Ferric reducing antioxidant power assay (FRAP) and anti-H. pylori activity were investigated in vitro. Results The results showed that the intragastric administration of zerumbone protected the gastric mucosa from the aggressive effect of ethanol-induced gastric ulcer, coincided with reduced submucosal edema and leukocyte infiltration. This observed gastroprotective effect of zerumbone was accompanied with a significant (p <0.05) effect of the compound to restore the lowered NP-SH and GSH levels, and to reduce the elevated MDA level into the gastric homogenate. Moreover, the compound induced HSP-70 up-regulation into the gastric tissue. Furthermore, zerumbone significantly (p <0.05) enhanced mucus production, showed intense PAS stain and maintained PG content near to the normal level. The compound exhibited antisecretory activity and an interesting minimum inhibitory concentration (MIC) against H. pylori strain. Conclusion The results of the present study revealed that zerumbone promotes ulcer protection, which might be attributed to the maintenance of mucus integrity, antioxidant activity, and HSP-70 induction. Zerumbone also exhibited antibacterial action against H. pylori. PMID:25798602

Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin

PubMed Central

Brines, Michael; Patel, Nimesh S. A.; Villa, Pia; Brines, Courtenay; Mennini, Tiziana; De Paola, Massimiliano; Erbayraktar, Zubeyde; Erbayraktar, Serhat; Sepodes, Bruno; Thiemermann, Christoph; Ghezzi, Pietro; Yamin, Michael; Hand, Carla C.; Xie, Qiao-wen; Coleman, Thomas; Cerami, Anthony

2008-01-01

Erythropoietin (EPO), a member of the type 1 cytokine superfamily, plays a critical hormonal role regulating erythrocyte production as well as a paracrine/autocrine role in which locally produced EPO protects a wide variety of tissues from diverse injuries. Significantly, these functions are mediated by distinct receptors: hematopoiesis via the EPO receptor homodimer and tissue protection via a heterocomplex composed of the EPO receptor and CD131, the β common receptor. In the present work, we have delimited tissue-protective domains within EPO to short peptide sequences. We demonstrate that helix B (amino acid residues 58–82) of EPO, which faces the aqueous medium when EPO is bound to the receptor homodimer, is both neuroprotective in vitro and tissue protective in vivo in a variety of models, including ischemic stroke, diabetes-induced retinal edema, and peripheral nerve trauma. Remarkably, an 11-aa peptide composed of adjacent amino acids forming the aqueous face of helix B is also tissue protective, as confirmed by its therapeutic benefit in models of ischemic stroke and renal ischemia–reperfusion. Further, this peptide simulating the aqueous surface of helix B also exhibits EPO's trophic effects by accelerating wound healing and augmenting cognitive function in rodents. As anticipated, neither helix B nor the 11-aa peptide is erythropoietic in vitro or in vivo. Thus, the tissue-protective activities of EPO are mimicked by small, nonerythropoietic peptides that simulate a portion of EPO's three-dimensional structure. PMID:18676614

Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin.

PubMed

Brines, Michael; Patel, Nimesh S A; Villa, Pia; Brines, Courtenay; Mennini, Tiziana; De Paola, Massimiliano; Erbayraktar, Zubeyde; Erbayraktar, Serhat; Sepodes, Bruno; Thiemermann, Christoph; Ghezzi, Pietro; Yamin, Michael; Hand, Carla C; Xie, Qiao-wen; Coleman, Thomas; Cerami, Anthony

2008-08-05

Erythropoietin (EPO), a member of the type 1 cytokine superfamily, plays a critical hormonal role regulating erythrocyte production as well as a paracrine/autocrine role in which locally produced EPO protects a wide variety of tissues from diverse injuries. Significantly, these functions are mediated by distinct receptors: hematopoiesis via the EPO receptor homodimer and tissue protection via a heterocomplex composed of the EPO receptor and CD131, the beta common receptor. In the present work, we have delimited tissue-protective domains within EPO to short peptide sequences. We demonstrate that helix B (amino acid residues 58-82) of EPO, which faces the aqueous medium when EPO is bound to the receptor homodimer, is both neuroprotective in vitro and tissue protective in vivo in a variety of models, including ischemic stroke, diabetes-induced retinal edema, and peripheral nerve trauma. Remarkably, an 11-aa peptide composed of adjacent amino acids forming the aqueous face of helix B is also tissue protective, as confirmed by its therapeutic benefit in models of ischemic stroke and renal ischemia-reperfusion. Further, this peptide simulating the aqueous surface of helix B also exhibits EPO's trophic effects by accelerating wound healing and augmenting cognitive function in rodents. As anticipated, neither helix B nor the 11-aa peptide is erythropoietic in vitro or in vivo. Thus, the tissue-protective activities of EPO are mimicked by small, nonerythropoietic peptides that simulate a portion of EPO's three-dimensional structure.

Identification of ion-channel modulators that protect against aminoglycoside-induced hair cell death

PubMed Central

Kenyon, Emma J.; Kirkwood, Nerissa K.; Kitcher, Siân R.; O’Reilly, Molly; Cantillon, Daire M.; Goodyear, Richard J.; Secker, Abigail; Baxendale, Sarah; Bull, James C.; Waddell, Simon J.; Whitfield, Tanya T.; Ward, Simon E.; Kros, Corné J.; Richardson, Guy P.

2017-01-01

Aminoglycoside antibiotics are used to treat life-threatening bacterial infections but can cause deafness due to hair cell death in the inner ear. Compounds have been described that protect zebrafish lateral line hair cells from aminoglycosides, but few are effective in the cochlea. As the aminoglycosides interact with several ion channels, including the mechanoelectrical transducer (MET) channels by which they can enter hair cells, we screened 160 ion-channel modulators, seeking compounds that protect cochlear outer hair cells (OHCs) from aminoglycoside-induced death in vitro. Using zebrafish, 72 compounds were identified that either reduced loading of the MET-channel blocker FM 1-43FX, decreased Texas red–conjugated neomycin labeling, or reduced neomycin-induced hair cell death. After testing these 72 compounds, and 6 structurally similar compounds that failed in zebrafish, 13 were found that protected against gentamicin-induced death of OHCs in mouse cochlear cultures, 6 of which are permeant blockers of the hair cell MET channel. None of these compounds abrogated aminoglycoside antibacterial efficacy. By selecting those without adverse effects at high concentrations, 5 emerged as leads for developing pharmaceutical otoprotectants to alleviate an increasing clinical problem. PMID:29263311

Identification of ion-channel modulators that protect against aminoglycoside-induced hair cell death.

PubMed

Kenyon, Emma J; Kirkwood, Nerissa K; Kitcher, Siân R; O'Reilly, Molly; Derudas, Marco; Cantillon, Daire M; Goodyear, Richard J; Secker, Abigail; Baxendale, Sarah; Bull, James C; Waddell, Simon J; Whitfield, Tanya T; Ward, Simon E; Kros, Corné J; Richardson, Guy P

2017-12-21

Aminoglycoside antibiotics are used to treat life-threatening bacterial infections but can cause deafness due to hair cell death in the inner ear. Compounds have been described that protect zebrafish lateral line hair cells from aminoglycosides, but few are effective in the cochlea. As the aminoglycosides interact with several ion channels, including the mechanoelectrical transducer (MET) channels by which they can enter hair cells, we screened 160 ion-channel modulators, seeking compounds that protect cochlear outer hair cells (OHCs) from aminoglycoside-induced death in vitro. Using zebrafish, 72 compounds were identified that either reduced loading of the MET-channel blocker FM 1-43FX, decreased Texas red-conjugated neomycin labeling, or reduced neomycin-induced hair cell death. After testing these 72 compounds, and 6 structurally similar compounds that failed in zebrafish, 13 were found that protected against gentamicin-induced death of OHCs in mouse cochlear cultures, 6 of which are permeant blockers of the hair cell MET channel. None of these compounds abrogated aminoglycoside antibacterial efficacy. By selecting those without adverse effects at high concentrations, 5 emerged as leads for developing pharmaceutical otoprotectants to alleviate an increasing clinical problem.

Alteration of foliar flavonoid chemistry induced by enhanced UV-B radiation in field-grown Pinus ponderosa, Quercus rubra and Pseudotsuga menziesii.

PubMed

Warren, Jeffrey M; Bassman, John H; Mattinson, D Scott; Fellman, John K; Edwards, Gerald E; Robberecht, Ronald

2002-03-01

Chromatographic analyses of foliage from several tree species illustrate the species-specific effects of UV-B radiation on both quantity and composition of foliar flavonoids. Pinus ponderosa, Quercus rubra and Pseudotsuga menziesii were field-grown under modulated ambient (1x) and enhanced (2x) biologically effective UV-B radiation. Foliage was harvested seasonally over a 3-year period, extracted, purified and the flavonoid fraction applied to a mu Bondapak/C(18) column HPLC system sampling at 254 nm. Total flavonoid concentrations in Quercus rubra foliage were more than twice (leaf area basis) that of the other species; Pseudotsuga menziesii foliage had intermediate levels and P. ponderosa had the lowest concentrations of total flavonoids. No statistically significant UV-B radiation-induced effects were found in total foliar flavonoid concentrations for any species; however, concentrations of specific compounds within each species exhibited significant treatment effects. Higher (but statistically insignificant) levels of flavonoids were induced by UV-B irradiation in 1- and 2-year-old P. ponderosa foliage. Total flavonoid concentrations in 2-year-old needles increased by 50% (1x ambient UV-B radiation) or 70% (2x ambient UV-B radiation) from that of 1-year-old tissue. Foliar flavonoids of Q. rubra under enhanced UV-B radiation tended to shift from early-eluting compounds to less polar flavonoids eluting later. There were no clear patterns of UV-B radiation effects on 1-year-old P. menziesii foliage. However, 2-year-old tissue had slightly higher foliar flavonoids under the 2x UV-B radiation treatment compared to ambient levels. Results suggest that enhanced UV-B radiation will alter foliar flavonoid composition and concentrations in forest tree species, which could impact tissue protection, and ultimately, competition, herbivory or litter decomposition.

Integrative “omic” analysis reveals distinctive cold responses in leaves and roots of strawberry, Fragaria × ananassa ‘Korona’

PubMed Central

Koehler, Gage; Rohloff, Jens; Wilson, Robert C.; Kopka, Joachim; Erban, Alexander; Winge, Per; Bones, Atle M.; Davik, Jahn; Alsheikh, Muath K.; Randall, Stephen K.

2015-01-01

To assess underlying metabolic processes and regulatory mechanisms during cold exposure of strawberry, integrative “omic” approaches were applied to Fragaria × ananassa Duch. ‘Korona.’ Both root and leaf tissues were examined for responses to the cold acclimation processes. Levels of metabolites, proteins, and transcripts in tissues from plants grown at 18°C were compared to those following 1–10 days of cold (2°C) exposure. When leaves and roots were subjected to GC/TOF-MS-based metabolite profiling, about 160 compounds comprising mostly structurally annotated primary and secondary metabolites, were found. Overall, ‘Korona’ showed a modest increase of protective metabolites such as amino acids (aspartic acid, leucine, isoleucine, and valine), pentoses, phosphorylated and non-phosphorylated hexoses, and distinct compounds of the raffinose pathway (galactinol and raffinose). Distinctive responses were observed in roots and leaves. By 2DE proteomics a total of 845 spots were observed in leaves; 4.6% changed significantly in response to cold. Twenty-one proteins were identified, many of which were associated with general metabolism or photosynthesis. Transcript levels in leaves were determined by microarray, where dozens of cold associated transcripts were quantitatively characterized, and levels of several potential key contributors (e.g., the dehydrin COR47 and GADb) to cold tolerance were confirmed by qRT-PCR. Cold responses are placed within the existing knowledge base of low temperature-induced changes in plants, allowing an evaluation of the uniqueness or generality of Fragaria responses in photosynthetic tissues. Overall, the cold response characteristics of ‘Korona’ are consistent with a moderately cold tolerant plant. PMID:26528299

Long-term treatment with a Yang-invigorating Chinese herbal formula produces generalized tissue protection against oxidative damage in rats.

PubMed

Chiu, Po Yee; Leung, Hoi Yan; Siu, Ada Hoi Ling; Chen, Na; Poon, Michel K T; Ko, Kam Ming

2008-02-01

Previous work in our laboratory has shown that long-term treatment with Vigconic 28 (VI-28), a Yang-invigorating Chinese herbal formula used for the promotion of overall wellness in Chinese medicine, can enhance the mitochondrial functional ability and antioxidant capacity in various tissues of both male and female rats. To investigate whether the VI-28 treatment regimen could afford tissue protection against oxidative injury, the effects of long-term VI-28 treatment (80 or 240 mg/kg/d x 30) on oxidative stress-induced tissue damage in various organs (brain, heart, liver, and kidney) were examined in female rats. The results indicated that long-term VI-28 treatment invariably protected against oxidative tissue damage in the rat models of cerebral/myocardial ischemia-reperfusion injury, CCl4 hepatotoxicity, and gentamicin nephrotoxicity. The tissue protection was associated with increases in the levels and activities of mitochondrial antioxidant components as well as with the preservation of mitochondrial structural integrity. This was evidenced by decreases in the sensitivity of mitochondria to Ca2+-induced permeability transition, and in the levels of mitochondrial malondialdehyde production, Ca2+ loading, and cytochrome c release in the tissues examined. Interestingly, the VI-28 treatment increased red cell CuZn-superoxide dismutase (CuZn-SOD) levels, and these levels correlated positively with the degree of tissue protection afforded by long-term VI-28 treatment in rats. The generalized tissue protection afforded by long-term VI-28 treatment may have clinical implications in the prevention of age-related diseases, and VI-28 treatment may possibly delay the aging process.

A hepatonephro-protective phenolic-rich extract from red onion (Allium cepa L.) peels.

PubMed

Ahmed, Atallah F; Al-Yousef, Hanan M; Al-Qahtani, Jawaher H; Al-Said, Mansour S

2017-09-01

Onion peel is a common bio-waste, occasionally used in traditional medicine in treatment of liver ailment and inflammation. However, a phytochemical and biological study is further required to provide the scientific evidence for this use. A phenolic-rich extract of red onion peels (coded as ACPE) was primarily prepared and then subjected to chromatographic separation. From the extract, six phenolic antioxidant compounds along with two phytosterols were isolated and identified by means of spectroscopic (NMR and MS) analyses. The in vivo protective activity of the ACPE against the oxidative stress induced by carbon tetrachloride (CCl4) free radicals, in liver and kidney, was assessed in rats. Relative to the CCl4-challenged animals, pre-treatment with ACPE could significantly ameliorate the hepatonephrolinked serum and tissue markers in a dose-dependent response. The flavonol- and phenolic acid-based nature of constituents, the high phenolic content (72.33±5.30 mg gallic acid equivalent per one gram) and the significant antioxidant capacity (>1/3 potency of rutin) of ACPE may be thus attributed strongly to the hepatonephro-protective and anti-inflammatory effect of ACPE. The results suggest that red onion peels can serve as a convenient and cost-effective source of high-value antioxidant nutraceuticals for protection against oxidative stress-related disorders.

Djulis (Chenopodium formosanum Koidz.) Water Extract and Its Bioactive Components Ameliorate Dermal Damage in UVB-Irradiated Skin Models.

PubMed

Hong, Yong-Han; Huang, Ya-Ling; Liu, Yao-Cheng; Tsai, Pi-Jen

2016-01-01

Dermal photoaging is a condition of skin suffering inappropriate ultraviolet (UV) exposure and exerts inflammation, tissue alterations, redness, swelling, and uncomfortable feelings. Djulis ( Chenopodium formosanum Koidz.) is a cereal food and its antioxidant and pigment constituents may provide skin protection from photoaging, but it still lacks proved experiments. In this study, protective effects of djulis extract (CFE) on UVB-irradiated skin were explored. The results showed that HaCaT cells with 150  μ g/mL CFE treatment had higher survival and less production of interleukin- (IL-) 6, matrix metalloprotease- (MMP-) 1, and reactive oxygen species (ROS) in UVB-irradiated conditions. Subsequently, in animal studies, mice supplemented with CFE (100 mg/kg BW) were under UVB irradiation and had thinner epidermis and lower IL-6 levels in skin layer. These data demonstrate that bioactive compounds possessing the potency of antiphotoaging exist in CFE. Following that, we found rutin and chlorogenic acid (10-100  μ M) could significantly increase cell viability and decrease the production of IL-6 in UVB models. Additionally, djulis pigment-betanin has no effect of increasing cell viability in this study. Our findings suggest CFE can protect skin against UV-induced damage and this protection is mainly from contributions of rutin and chlorogenic acid.

Evaluating nephrotoxicity of high-molecular-weight organic compounds in drinking water from lignite aquifers

USGS Publications Warehouse

Bunnell, J.E.; Tatu, C.A.; Lerch, H.E.; Orem, W.H.; Pavlovic, N.

2007-01-01

High-molecular-weight organic compounds such as humic acids and/or fulvic acids that are naturally mobilized from lignite beds into untreated drinking-water supplies were suggested as one possible cause of Balkan endemic nephropathy (BEN) and cancer of the renal pelvis. A lab investigation was undertaken in order to assess the nephrotoxic potential of such organic compounds using an in vitro tissue culture model. Because of the infeasibility of exposing kidney tissue to low concentrations of organics for years in the lab, tangential flow ultrafiltration was employed to hyperconcentrate samples suitable for discerning effects in the short time frames necessitated by tissue culture systems. Effects on HK-2 kidney cells were measured using two different cell proliferation assays (MTT and alamarBlue). Results demonstrated that exposure of kidney tissue to high-molecular-weight organics produced excess cell death or proliferation depending on concentration and duration of exposure. Copyright ?? Taylor & Francis Group, LLC.

A method for direct assessment of tissue-nonspecific alkaline phosphatase (TNAP) inhibitors in blood samples.

PubMed

Sergienko, Eduard A; Sun, Qing; Ma, Chen-Ting

2013-01-01

Tissue nonspecific alkaline phosphatase (TNAP) is one of four human alkaline phosphatases (AP), a family of exocytic enzymes that catalyze hydrolysis of phospho-monoesters in bone, liver, kidney, and various other tissues. Overexpression of TNAP gives rise to excessive bone and soft tissue mineralization, including blood vessel calcification. Our prior screening campaigns have found several leads against this attractive therapeutic target using in vitro assay with a recombinant enzyme; these compounds were further optimized using medicinal chemistry approaches. To prioritize compounds for their use in animal models, we have designed and developed a biomarker assay for in situ detection of TNAP activity within human and mouse blood samples at physiological pH. This assay is suitable for screening compounds in 1,536-well plates using blood plasma from different mammalian species. The user may choose from two different substrates based on the need for greater assay simplicity or sensitivity.

Colonization and effector functions of innate lymphoid cells in mucosal tissues

PubMed Central

Kim, Myunghoo; Kim, Chang H.

2016-01-01

Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. PMID:27365193

Hydrogel tissue construct-based high-content compound screening.

PubMed

Lam, Vy; Wakatsuki, Tetsuro

2011-01-01

Current pharmaceutical compound screening systems rely on cell-based assays to identify therapeutic candidates and potential toxicities. However, cells grown on 2D substrata or in suspension do not exhibit the mechanical or physiological properties of cells in vivo. To address this limitation, the authors developed an in vitro, high-throughput, 3D hydrogel tissue construct (HTC)-based assay system to quantify cell and tissue mechanical properties and multiple parameters of physiology. HTC mechanics was quantified using an automated device, and physiological status was assessed using spectroscopy-based indicators that were read on microplate readers. To demonstrate the application of this system, the authors screened 4 test compounds--rotenone (ROT), cytochalasin D (CD), 2,4-dinitrophenol (DNP), and Rho kinase inhibitor (H-1152)--for their ability to modulate HTC contractility without affecting actin integrity, mitochondrial membrane potential (MMP), or viability. All 4 compounds dose-dependently reduced HTC contractility. However, ROT was toxic, DNP dissipated MMP, and CD reduced both intracellular F-actin and viability. H-1152 was found to be the best candidate compound since it reduced HTC contractility with minimal side effects. The authors propose that their HTC-based assay system can be used to screen for compounds that modulate HTC contractility and assess the underlying physiological mechanism(s) of compound activity and toxicity.

Perfluorinated compounds in fish from U.S. urban rivers and the Great Lakes.

PubMed

Stahl, Leanne L; Snyder, Blaine D; Olsen, Anthony R; Kincaid, Thomas M; Wathen, John B; McCarty, Harry B

2014-11-15

Perfluorinated compounds (PFCs) have recently received scientific and regulatory attention due to their broad environmental distribution, persistence, bioaccumulative potential, and toxicity. Studies suggest that fish consumption may be a source of human exposure to perfluorooctane sulfonate (PFOS) or long-chain perfluorocarboxylic acids. Most PFC fish tissue literature focuses on marine fish and waters outside of the United States (U.S.). To broaden assessments in U.S. fish, a characterization of PFCs in freshwater fish was initiated on a national scale using an unequal probability design during the U.S. Environmental Protection Agency's (EPA's) 2008-2009 National Rivers and Streams Assessment (NRSA) and the Great Lakes Human Health Fish Tissue Study component of the 2010 EPA National Coastal Condition Assessment (NCCA/GL). Fish were collected from randomly selected locations--164 urban river sites and 157 nearshore Great Lake sites. The probability design allowed extrapolation to the sampled population of 17,059 km in urban rivers and a nearshore area of 11,091 km(2) in the Great Lakes. Fillets were analyzed for 13 PFCs using high-performance liquid chromatography tandem mass spectrometry. Results showed that PFOS dominated in frequency of occurrence, followed by three other longer-chain PFCs (perfluorodecanoic acid, perfluoroundecanoic acid, and perfluorododecanoic acid). Maximum PFOS concentrations were 127 and 80 ng/g in urban river samples and Great Lakes samples, respectively. The range of NRSA PFOS detections was similar to literature accounts from targeted riverine fish sampling. NCCA/GL PFOS levels were lower than those reported by other Great Lakes researchers, but generally higher than values in targeted inland lake studies. The probability design allowed development of cumulative distribution functions (CDFs) to quantify PFOS concentrations versus the sampled population, and the application of fish consumption advisory guidance to the CDFs resulted in an estimation of the proportion of urban rivers and the Great Lakes that exceed human health protection thresholds. Copyright © 2014. Published by Elsevier B.V.

Intraosseous Erythropoietin for Acute Tissue Protection in Battlefield Casualties Suffering Hypovolemic Shock

DTIC Science & Technology

2012-11-01

Award Number: W81XWH-11-2-0019 TITLE: Intraosseous Erythropoietin for Acute Tissue Protection in Battlefield Casualties Suffering Hypovolemic...REPORT TYPE Final 3. DATES COVERED 4 October 2010- 3 October 2012 4. TITLE AND SUBTITLE Intraosseous Erythropoietin for Acute Tissue Protection in...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT- The project investigated whether intraosseous administration of erythropoietin (EPO) during

Different responses of vanillic acid, a phenolic compound, in HTC cells: cytotoxicity, antiproliferative activity, and protection from DNA-induced damage.

PubMed

Almeida, I V; Cavalcante, F M L; Vicentini, V E P

2016-12-19

The consumption of healthy and natural foods has increased over the last few years, primarily because these foods are rich in substances with biological properties of interest, such as exerting anticancer effects and decreasing oxidative stress in living tissues. These foods support adequate nutrition, maintain health, and improve quality of life. Vanillic acid (VA) is a phenolic compound used widely in the food industry as a flavoring, preservative, and food additive. VA can be found in various cereals, whole grains, fruits, herbs, green tea, juices, beers, and wines and possesses antioxidant, hepatoprotective, cardioprotective, and antiapoptotic activities. Studying the cytotoxicity as well as the mutagenic and antimutagenic effects of different concentrations of VA in Rattus norvegicus hepatoma cells (HTC) can identify new cellular activities of this substance. Concentrations up to 100 µM VA are not cytotoxic to HTC cells in a MTT [3-(4,5-dimethilthiazol-2-yl)-2,5-diphenil tetrazolium bromide] assay after 96-h exposure; therefore, VA does not compromise mitochondrial activity. Similarly, concentrations up to 500 µM do not compromise plasma membrane integrity. VA at 10 and 50 µM showed no mutagenic/clastogenic effects, as no significant micronuclei induction was observed. VA 10 µM presented no antiproliferative activity and reduced the cytotoxicity induced by benzo[a]pyrene. The antimutagenic activity of 10 µM VA was observed by the simultaneous, pre-, and post-treatments, as the phenolic compound significantly reduced the frequency of micronuclei induced by the mutagen. These results indicate that VA exerts different responses in HTC cells. Low concentrations present no cytotoxic, mutagenic, or antiproliferative effects and protect cells from DNA damage.

Occurrence and distribution of selected contaminants in public drinking-water supplies in the surficial aquifer in Delaware

USGS Publications Warehouse

Ferrari, Matthew J.

2001-01-01

Water samples were collected from August through November 2000 from 30 randomly selected public drinking-water supply wells screened in the unconfined aquifer in Delaware, and analyzed to assess the occurrence and distribution of selected pesticide compounds, volatile organic compounds, major inorganic ions, and nutrients. Water from a subset of 10 wells was sampled and analyzed for radium and radon. The average age of ground water entering the well screens in all the wells was determined to be generally less than 20 years. Low concentrations of pesticide compounds and volatile organic compounds were detected throughout the State of Delaware, with several compounds often detected in each water sample. Pesticide and metabolite (pesticide degradation products) concentrations were generally less than 1 microgram per liter, and were detected in sam-ples from 27 of 30 wells. Of the 45 pesticides and 13 metabolites analyzed, 19 compounds (13 pesticides and 6 metabolites) were detected in at least 1 of the 30 samples. Desethylatrazine, alachlor ethane sulfonic acid, metolachlor ethane sulfonic acid, metolachlor, and atrazine were the most frequently detected pesticide compounds, and were present in at least half the samples. None of the pesticide detections was above the U.S. Environmental Protection Agency's Primary Maximum Contaminant Levels or Health Advisories. Volatile organic compounds also were present at low concentrations (generally less than 1 microgram per liter) in samples from all 30 wells. Of the 85 volatile organic com-pounds analyzed, 34 compounds were detected in at least 1 of the 30 samples. Chloroform, tetrachloroethene, and methyl tert-butyl ether were the most frequently detected volatile organic compounds, and were found in at least half the samples. None of the volatile organic compound detections was above U.S. Environmental Protection Agency's Primary Maximum Contaminant Levels or Health Advisories. A few samples contained compounds with concentrations above the U.S. Environmental Protection Agency's Primary Maximum Contaminant Levels or Secondary Maximum Contaminant Levels for inorganic compounds and radionuclides. One sample out of 30 contained a concentration of nitrite plus nitrate above the U.S. Environmental Protection Agency's Primary Maximum Contaminant Level of 10 milligrams per liter as nitrogen. Iron and manganese concentrations above the U.S. Environmental Protection Agency's Secondary Maximum Contaminant Levels were found in 7 of 30 ground-water samples, most of them from Sussex County. In the 10 wells sampled for radionuclides, only one sample had detectable levels of radium-224 and -226, and another sample contained detectable levels of radium-228; both of these samples also had detectable gross-alpha and gross-beta activities. None of these activities were above the U.S. Environ-mental Protection Agency's Primary Maximum Contaminant Levels or Secondary Maximum Contaminant Levels. Radon was detected in all 10 samples, but was above the current U.S. Environmental Protection Agency's proposed Primary Maximum Contaminant Level of 300 picocuries per liter in only one sample.

Synthesis, Antiinflammatory and Antimicrobial Activity of Some New 1-(3-Phenyl-3,4-Dihydro-2H-1,3-Benzoxazin-6-yl)-Ethanone Derivatives.

PubMed

Akhter, Mymoona; Husain, A; Akhter, N; Khan, M S Y

2011-01-01

Synthesis of title compounds (4a-j) was carried out by following aminomethylation Mannich reaction. Test compounds were effective in inhibiting edema induced by carrageenan. The percent inhibition obseved was in the range of 25-83.3%. Compound (4c, e, h and j) were also tested for analgesic effect and showed percent protection ranging between 57-65%. All the synthesized compounds were active against E. coli and S. aureus but only compounds (4 b, c, e, i and j) were active against B. subtilis. All these compound were also found active against A. niger. Compound 4j was the most active compound with 83.3% inhibition of edema, 65.35% percent protection and inhibited all the three bacterial strains.

Measurement of barrier tissue integrity with an organic electrochemical transistor.

PubMed

Jimison, Leslie H; Tria, Scherrine A; Khodagholy, Dion; Gurfinkel, Moshe; Lanzarini, Erica; Hama, Adel; Malliaras, George G; Owens, Róisín M

2012-11-20

The integration of an organic electrochemical transistor with human barrier tissue cells provides a novel method for assessing toxicology of compounds in vitro. Minute variations in paracellular ionic flux induced by toxic compounds are measured in real time, with unprecedented temporal resolution and extreme sensitivity. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Trifluoroacetylated tyrosine-rich D-tetrapeptides have potent antioxidant activity.

PubMed

Sandomenico, Annamaria; Severino, Valeria; Apone, Fabio; De Lucia, Adriana; Caporale, Andrea; Doti, Nunzianna; Russo, Anna; Russo, Rosita; Rega, Camilla; Del Giacco, Tiziana; Falcigno, Lucia; Ruvo, Menotti; Chambery, Angela

2017-03-01

The term "oxidative stress" indicates a set of chemical reactions unleashed by a disparate number of events inducing DNA damage, lipid peroxidation, protein modification and other effects, which are responsible of altering the physiological status of cells or tissues. Excessive Reactive Oxygen Species (ROS) levels may accelerate ageing of tissues or induce damage of biomolecules thus promoting cell death or proliferation in dependence of cell status and of targeted molecules. In this context, new antioxidants preventing such effects may have a relevant role as modulators of cell homeostasis and as therapeutic agents. Following an approach of peptide libraries synthesis and screening by an ORAC FL assay, we have isolated potent anti-oxidant compounds with well-defined structures. Most effective peptides are N-terminally trifluoroacetylated (CF 3 ) and have the sequence tyr-tyr-his-pro or tyr-tyr-pro-his. Slight changes in the sequence or removal of the CF 3 group strongly reduced antioxidant ability, suggesting an active role of both the fluorine atoms and of peptide structure. We have determined the NMR solution structures of the active peptides and found a common structural motif that could underpin the radical scavenging activity. The peptides protect keratinocytes from exogenous oxidation, thereby from potential external damaging cues, suggesting their use as skin ageing protectant and as cell surviving agents. Copyright © 2017 Elsevier Inc. All rights reserved.

Black Soybean Extract Protects Against TMT-Induced Cognitive Defects in Mice

PubMed Central

Jeong, Ji Hee; Jo, Yu Na; Kim, Hyeon Ju; Jin, Dong Eun; Kim, Dae-Ok

2014-01-01

Abstract To find a neuroactive compound with a potent inhibitory effect on acetylcholinesterase (AChE) and in vivo anti-amnesic activity from natural resources, we evaluated anthocyanins and nonanthocyanins from black soybean extract. Nonanthocyanins from black soybean extract were the most potent and dose-dependent AChE inhibitors. Intracellular reactive oxygen species accumulation resulting from H2O2 treatment was significantly decreased compared with cells treated with H2O2 only. Nonanthocyanins were also neuroprotective against H2O2 treated neurotoxicity by 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assay. Finally, nonanthocyanins from black soybean in the preadministration group attenuated trimethyltin (TMT)-induced memory injury in both in vivo tests. AChE, prepared from mice brain tissues, was inhibited by nonanthocyanins from black soybean in a dose-dependent manner. Malondialdehyde generation in the brain homogenates of mice treated with nonanthocyanins from black soybean was decreased. We concluded that nonanthocyanins from black soybean had an efficacious in vitro AChE inhibitory activity, and protected against H2O2-induced neurotoxicity. In addition, our findings suggest that nonanthocyanins from black soybean may improve the TMT-induced learning and memory deficit because of AChE inhibition of mice brain tissue. Consequently, these results demonstrate that the nonanthocyanins from black soybean could possess a wide range of beneficial activities for neurodegenerative disorders. PMID:24456358

Heat generated by Er:YAG laser in the pulp chamber of teeth submitted to removal of dental tissue and composite resin

NASA Astrophysics Data System (ADS)

Zanin, Fatima; Brugnera, Aldo, Jr.; Pecora, Jesus D.; Pinheiro, Antonio; Spano, Julio; Barbin, Eduardo; Marchesan, Melissa A.

2004-05-01

The knowledge about and control of thermal energy produced by Er:YAG laser after irradiating hard dental tissues and compound resin is important because the pulp, like all vital biological tissue, has a certain capacity for supporting stimulus. The objective of this study was to analyze the thermal variation generated by Er:YAG laser (λ=2.94μm) during the preparation of a Class I cavity in the dental structure and in the removal of microhybrid Z100 (3M) compound resin. An evaluation was made of 30 maxillary human pre-molar teeth from the bank of the Endodontic Laboratory Center of Ribeirao Preto Dental School, Brasil. The sample was divided into 6 groups of 5 teeth each: Group 1, preparation of Class I cavity with Er:YAG laser (350mJ, 3Hz, 343 impulses, 120J, 113 seconds); Group 2, preparation of Class I cavity with Er:YAG laser (350mJ, 4Hz, 343 impulses, 120J, 81 seconds); Group 3, preparation of Class I cavity with Er:YAG laser (350mJ, 6Hz, 343 impulses, 120J, 58 seconds); Group 4, removal of compound resin from Class I preparation with Er:YAG laser (350mJ, 3Hz, 258 impulses, 90J, 85 seconds); Group 5, removal of compound resin from Class I preparation with Er:YAG laser (350mJ, 4Hz, 258 impulses, 90J, 67 seconds); Group 6, removal of compound resin from Class I preparation with Er:YAG laser (350mJ, 6Hz, 258 impulses, 42 seconds). The laser used was KaVo Key 2 (Biberach, Germany), λ=2,94μm, P=3 Watts, pulse duration of 250μs, with air-water cooling. The increase in temperature during dental preparation and the removal of the compound resin was evaluated by means of a Tektronix DMM916 Thermocouple (Consitec, Brasil). The results showed that the application of laser for the removal of the hard dental tissues and for the removal of compound resins with the pulse frequencies 3, 4 and 6 Hz did not generate heating greater than 3.1°C and remained within the histopathological limits permitted for pulp tissue (5.5°C) and there was a significant statistical difference between the heat generated by the application of laser in the removal of the hard dental tissues and in the removal of compound resins (p<0.01). The average increase in temperature of the compound resin component was greater than the tooth.

White Adipose Tissue Is a Reservoir for Memory T Cells and Promotes Protective Memory Responses to Infection.

PubMed

Han, Seong-Ji; Glatman Zaretsky, Arielle; Andrade-Oliveira, Vinicius; Collins, Nicholas; Dzutsev, Amiran; Shaik, Jahangheer; Morais da Fonseca, Denise; Harrison, Oliver J; Tamoutounour, Samira; Byrd, Allyson L; Smelkinson, Margery; Bouladoux, Nicolas; Bliska, James B; Brenchley, Jason M; Brodsky, Igor E; Belkaid, Yasmine

2017-12-19

White adipose tissue bridges body organs and plays a fundamental role in host metabolism. To what extent adipose tissue also contributes to immune surveillance and long-term protective defense remains largely unknown. Here, we have shown that at steady state, white adipose tissue contained abundant memory lymphocyte populations. After infection, white adipose tissue accumulated large numbers of pathogen-specific memory T cells, including tissue-resident cells. Memory T cells in white adipose tissue expressed a distinct metabolic profile, and white adipose tissue from previously infected mice was sufficient to protect uninfected mice from lethal pathogen challenge. Induction of recall responses within white adipose tissue was associated with the collapse of lipid metabolism in favor of antimicrobial responses. Our results suggest that white adipose tissue represents a memory T cell reservoir that provides potent and rapid effector memory responses, positioning this compartment as a potential major contributor to immunological memory. Published by Elsevier Inc.

78 FR 37973 - Change of Address for Region 7; Technical Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-25

... recordkeeping requirements, Sulfur oxides, Volatile organic compounds. 40 CFR Part 59 Environmental protection... requirements, Volatile organic compounds. 40 CFR Part 60 Environmental protection, Administrative practice and..., Cement industry, Chemicals, Coal, Copper, Dry cleaners, Electric power plants, Fertilizers, Fluoride...

Date Palm (Phoenix dactylifera) Fruits as a Potential Cardioprotective Agent: The Role of Circulating Progenitor Cells

PubMed Central

Alhaider, Ibrahim A.; Mohamed, Maged E.; Ahmed, K. K. M.; Kumar, Arun H. S.

2017-01-01

Context: Date palms, along with their fruits’ dietary consumption, possess enormous medicinal and pharmacological activities manifested in their usage in a variety of ailments in the various traditional systems of medicine. In recent years, the identification of progenitor cells in the adult organ systems has opened an altogether new approach to therapeutics, due to the ability of these cells to repair the damaged cells/tissues. Hence, the concept of developing therapeutics, which can mobilize endogenous progenitor cells, following tissue injury, to enhance tissue repair process is clinically relevant. Objectives: The present study investigates the potential of date of palm fruit extracts in repairing tissue injury following myocardial infarction (MI) potentially by mobilizing circulating progenitor cells. Methods: Extracts of four different varieties of date palm fruits common in Saudi Arabia eastern provision were scrutinized for their total flavonoid, total phenolic, in vitro antioxidant capacity, as well as their effects on two different rodent MI models. Results: High concentrations of phenolic and flavonoid compounds were observed in date palm fruit extracts, which contributed to the promising antioxidant activities of these extracts and the observed high protective effect against various induced in vivo MI. The extracts showed ability to build up reserves and to mobilize circulating progenitor cells from bone marrow and peripheral circulation to the site of myocardial infraction. Conclusion: Date palm fruit extracts have the potential to mobilize endogenous circulating progenitor cells, which can promote tissue repair following ischemic injury. PMID:28928656

Date Palm (Phoenix dactylifera) Fruits as a Potential Cardioprotective Agent: The Role of Circulating Progenitor Cells.

PubMed

Alhaider, Ibrahim A; Mohamed, Maged E; Ahmed, K K M; Kumar, Arun H S

2017-01-01

Context: Date palms, along with their fruits' dietary consumption, possess enormous medicinal and pharmacological activities manifested in their usage in a variety of ailments in the various traditional systems of medicine. In recent years, the identification of progenitor cells in the adult organ systems has opened an altogether new approach to therapeutics, due to the ability of these cells to repair the damaged cells/tissues. Hence, the concept of developing therapeutics, which can mobilize endogenous progenitor cells, following tissue injury, to enhance tissue repair process is clinically relevant. Objectives: The present study investigates the potential of date of palm fruit extracts in repairing tissue injury following myocardial infarction (MI) potentially by mobilizing circulating progenitor cells. Methods: Extracts of four different varieties of date palm fruits common in Saudi Arabia eastern provision were scrutinized for their total flavonoid, total phenolic, in vitro antioxidant capacity, as well as their effects on two different rodent MI models. Results: High concentrations of phenolic and flavonoid compounds were observed in date palm fruit extracts, which contributed to the promising antioxidant activities of these extracts and the observed high protective effect against various induced in vivo MI. The extracts showed ability to build up reserves and to mobilize circulating progenitor cells from bone marrow and peripheral circulation to the site of myocardial infraction. Conclusion: Date palm fruit extracts have the potential to mobilize endogenous circulating progenitor cells, which can promote tissue repair following ischemic injury.

Boron Hazards to Fish, Wildlife, and Invertebrates: A Synoptic Review

USGS Publications Warehouse

Eisler, R.

1990-01-01

Ecological and toxicological aspects of boron (B) in the environment are reviewed, with emphasis on natural resources. Subtopics covered include environmental chemistry, background concentrations, effects, and current recommendations for the protection of living resources. Boron is not now considered essential in mammalian nutrition, although low dietary levels protect against fluorosis and bone demineralization. Excessive consumption (i.e., >1,000 mg B/kg diet, >15 mg B/kg body weight daily, >1.0 mg B/L drinking water, or >210 mg B/kg body weight in a single dose) adversely affects growth, survival, or reproduction in sensitive mammals. Boron and its compounds are potent teratogens when applied directly to the mammalian embryo, but there is no evidence of mutagenicity or carcinogenicity. Boron`s unique affinity for cancerous tissues has been exploited in neutron capture radiation therapy of malignant human brain tumors. Current boron criteria recommended for the protection of sensitive species include <0.3 mg B/L in crop irrigation waters, <1.0 mg B/L for aquatic life, <5.0 mg B/L in livestock drinking waters, <30 mg B/kg in waterfowl diets, and <100 mg B/kg in livestock diets.

Magnolol protects pancreatic β-cells against methylglyoxal-induced cellular dysfunction.

PubMed

Suh, Kwang Sik; Chon, Suk; Jung, Woon-Won; Choi, Eun Mi

2017-11-01

Chronic hyperglycemia aggravates insulin resistance, in part due to increased formation of advanced glycation end-products (AGEs). Methylglyoxal (MG), a major precursor of AGEs, accumulates abnormally in various tissues and organs and participates in oxidative damage. We investigated the insulinotropic benefits of magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, in pancreatic β-cells exposed to MG in vitro. When exposed to cytotoxic levels of MG for 48 h, RIN-m5F β-cells exhibited a significant loss of viability and impaired insulin secretion, whereas pretreatment with magnolol protected against MG-induced cell death and decreased insulin secretion. Moreover, magnolol increased the expression of genes involved in β-cell survival and function, including Ins2 and PDX1. Furthermore, magnolol increased the levels of AMPK phosphorylation, SIRT1, and PGC1α in RIN-5F β-cells. In addition, magnolol increased the activity of glyoxalase I and decreased the levels of MG-modified protein adducts, which suggests that magnolol protects against MG-induced protein glycation. Taken together, the results indicate the potential application of magnolol as an intervention against MG-induced hyperglycemia. Copyright © 2017 Elsevier B.V. All rights reserved.

Protective Effect of Sundarban Honey against Acetaminophen-Induced Acute Hepatonephrotoxicity in Rats

PubMed Central

Tanvir, E. M.; Gan, Siew Hua; Parvez, Mashud; Aminul Islam, Md.; Khalil, Md. Ibrahim

2014-01-01

Honey, a supersaturated natural product of honey bees, contains complex compounds with antioxidant properties and therefore has a wide a range of applications in both traditional and modern medicine. In the present study, the protective effects of Sundarban honey from Bangladesh against acetaminophen- (APAP-) induced hepatotoxicity and nephrotoxicity in experimental rats were investigated. Adult male Wistar rats were pretreated with honey (5 g/kg) for 4 weeks, followed by the induction of hepatotoxicity and nephrotoxicity via the oral administration of a single dose of APAP (2 g/kg). Organ damage was confirmed by measuring the elevation of serum alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), total protein (TP), total bilirubin (TB), urea, creatinine, and malondialdehyde (MDA). Histopathological alterations observed in the livers and the kidneys further confirmed oxidative damage to these tissues. Animals pretreated with Sundarban honey showed significantly markedly reduced levels of all of the investigated parameters. In addition, Sundarban honey ameliorated the altered hepatic and renal morphology in APAP-treated rats. Overall, our findings indicate that Sundarban honey protects against APAP-induced acute hepatic and renal damage, which could be attributed to the honey's antioxidant properties. PMID:25530774

Protective effects of sodium selenite supplementation against irradiation-induced damage in non-cancerous human esophageal cells.

PubMed

Puspitasari, Irma M; Yamazaki, Chiho; Abdulah, Rizky; Putri, Mirasari; Kameo, Satomi; Nakano, Takashi; Koyama, Hiroshi

2017-01-01

The administration of radioprotective compounds is one approach to preventing radiation damage in non-cancerous tissues. Therefore, radioprotective compounds are crucial in clinical radiotherapy. Selenium is a radioprotective compound that has been used in previous clinical studies of radiotherapy. However, evidence regarding the effectiveness of selenium in radiotherapy and the mechanisms underlying the selenium-induced reduction of the side effects of radiotherapy remains insufficient. To further investigate the effectiveness of selenium in radiotherapy, the present study examined the protective effects of sodium selenite supplementation administered prior to X-ray radiation treatment in CHEK-1 non-cancerous human esophageal cells. Sodium selenite supplementation increased glutathione peroxidase 1 (GPx-1) activity in a dose- and time-dependent manner. The sodium selenite dose that induced the highest GPx-1 activity was determined to be 50 nM for 72 h prior to radiotherapy. The half-maximal inhibitory concentration of sodium selenite in CHEK-1 cells was 3.6 µM. Sodium selenite supplementation increased the survival rate of the cells in a dose-dependent manner and enhanced the degree of cell viability at 72 h post-irradiation (P<0.05). Combined treatment with 50 nM sodium selenite and 2 gray (Gy) X-ray irradiation decreased the number of sub-G 1 cells from 5.9 to 4.2% (P<0.05) and increased the proportion of G 1 cells from 58.8 to 62.1%, compared with 2 Gy X-ray irradiation alone; however, this difference was not statistically significant (P=1.00). Western blot analysis revealed that treatment with 2 Gy X-ray irradiation significantly increased the expression levels of cleaved poly (ADP-ribose) polymerase (PARP; P<0.05). In addition, combined treatment with 50 nM sodium selenite and 2 Gy X-ray irradiation reduced the expression levels of cleaved PARP protein, compared with 2 Gy X-ray irradiation alone; however, this reduction was not statistically significant (P=0.423). These results suggest that 50 nM sodium selenite supplementation administered for 72 h prior to irradiation may protect CHEK-1 cells from irradiation-induced damage by inhibiting irradiation-induced apoptosis. Therefore, sodium selenite is a potential radioprotective compound for non-cancerous cells in clinical radiotherapy.

Autoradiographic identification of acetylcholine in the rabbit retina

PubMed Central

1979-01-01

Rabbit retinas were studied in vitro under conditions known to maintain their physiological function. Retinas incubated in the presence of [3H]choline synthesized substantial amounts of both [3H]phosphorylcholine and [3H]acetylcholine. With time, [3H]phosphorylcholine proceeded into phospholipids, primarily phosphatidylcholine. Retinas pulse-labeled by a 15-min exposure to 0.3 microM [3H]choline were incubated for a subsequent hour under chase conditions designed either to retain newly synthesized acetylcholine within synapses or to promote its release. At the end of this time the two groups of retinas were found to contain equal amounts of radioactivity in the phospholipid pathway, but only the retinas incubated under the acetylcholine-protecting conditions contained [3H]acetylcholine. Freeze-dried, vacuum-embedded tissue from each retina was autoradiographed on dry emulsion. All retinas showed silver grains over the photoreceptor cells and faint labeling of all ganglion cells. In the retinas that contained [3H]acetylcholine, silver grains also accumulated densely over a few cells with the position of amacrine cells, over a subset of the cells of the ganglion cell layer, and in two bands over the inner plexiform layer. Fixation of the retina with aqueous osmium tetroxide retained only the radioactive compounds located in the photoreceptor and ganglion cells. Sections from freeze- dried tissue lost their water-soluble choline metabolites when exposed to water, and autoradiography of such sections again revealed radioactivity primarily in the photoreceptor and ganglion cells. Radioactive compounds extracted from the sections were found to faithfully reflect those present in the tissue before processing; analysis of the compounds eluted from sections microdissected along the outer plexiform layer showed [3H]acetylcholine to have been synthesized only by cells of the inner retina. Taken together, these results indicate that the photoreceptor and ganglion cells are distinguished by a rapid synthesis of choline-containing phospholipids, while acetylcholine synthesis is restricted to a few cells at both margins of the inner plexiform layer. They imply that the only neurons to release acetylcholine within the rabbit retina are a small group of probable amacrine cells. PMID:92476

Colonization and effector functions of innate lymphoid cells in mucosal tissues.

PubMed

Kim, Myunghoo; Kim, Chang H

2016-10-01

Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Role of the modulation of CYP1A1 expression and activity in chemoprevention.

PubMed

Badal, S; Delgoda, R

2014-07-01

As one of the main extra-hepatic cytochrome P450 (CYP) enzymes, CYP1A1 has been comprehensively investigated for its ability to metabolize both exogenous and endogenous compounds into their carcinogenic derivatives. These derivatives are linked to cancer initiation and progression. The compound benzo-a-pyrene (BaP), a copious and noxious compound present in coal tar, automobile exhaust fumes, cigarette smoke and charbroiled food, is metabolised by CYP1A1 and has been studied in great detail. Other compounds reliant on the same enzyme for their activation include 7,12 dimethylbenz(a)anthracene (DMBA) and heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). This review takes an in-depth look at a number of phytochemicals, plant extracts and a few synthetic compounds that have been researched and deemed potential chemopreventives via their interaction with the activity and expression of CYP1A1. It will also review a useful active site model of CYP1A1. Based on inhibitors of CYP1A1 that have demonstrated in vivo use as chemopreventors, CYP1A1 is a useful initial target for screening compounds with such potential, with the use of rapid in vitro and/or in silico assessments. Chemoprevention is a means by which healthy tissues are protected via the prevention, inhibition or reversal of carcinogenesis. This review focuses on one important pathway of carcinogenesis and identifies the important role that CYP1A1 plays in that pathway. It is hoped that highlighting the importance of such a key target, will help revive further research into and application of inhibitors of CYP1A1 towards generating improved chemopreventors. Copyright © 2014 John Wiley & Sons, Ltd.

Effects of 3 Feeding Modes on the Volatile and Nonvolatile Compounds in the Edible Tissues of Female Chinese Mitten Crab (Eriocheir sinensis).

PubMed

Zhuang, Kejin; Wu, Na; Wang, Xichang; Wu, Xugan; Wang, Shuai; Long, Xiaowen; Wei, Xuan

2016-04-01

To reveal the impact of different feeding modes on the flavor quality of female Chinese mitten crab (Eriocheir sinensis) this study was conducted to compare the sensory evaluation scores, flavor compounds in meat and hepatopancreas of female E. sinensis fed with 3 feeding modes, that is, natural diets (NDs), traditional diets (TDs), and formulated diets (FDs). The result showed that crabs fed with ND had significantly lower sensory scores than the other 2 feeding modes in both edible tissues. The odor and taste profiles were evaluated by Electronic nose (E-nose) and tongue (E-tongue) techniques, respectively; results of perchloric acid showed each edible tissue had significant differences among the 3 modes. Contents of volatile compounds were measured by Headspace-solid phase micro extraction combined with gas chromatography-mass spectrometer. A total of 35 and 44 volatile compounds were identified in meat and hepatopancreas, respectively. ND mode of meat had the highest relative odor activity value (ROAV) summation among the 3 diet modes. TD mode of hepatopancreas had significantly higher ROAV summations. Based on the analysis of free amino acids and 5'-nucleotides, nonvolatile compounds were evaluated by equivalent umami concentration (EUC) and taste active values (TAVs) methods. For both meat and hepatopancreas, TD had the highest contents of umami amino acid, as for the 5'-nucleotide, FD had the highest 5'-inosin monophosphate concentrations. Overall, the EUC and TAVs of TD were higher than that of FD, whereas ND mode had the lowest values in the 2 edible tissues. In conclusion, TD mode had the best performance in terms of sensory evaluation, ROAVs of aroma-active compounds, and nonvolatile active compounds. © 2016 Institute of Food Technologists®

A compound scattering pdf for the ultrasonic echo envelope and its relationship to K and Nakagami distributions.

PubMed

Shankar, P Mohana

2003-03-01

A compound probability density function (pdf) is presented to describe the envelope of the backscattered echo from tissue. This pdf allows local and global variation in scattering cross sections in tissue. The ultrasonic backscattering cross sections are assumed to be gamma distributed. The gamma distribution also is used to model the randomness in the average cross sections. This gamma-gamma model results in the compound scattering pdf for the envelope. The relationship of this compound pdf to the Rayleigh, K, and Nakagami distributions is explored through an analysis of the signal-to-noise ratio of the envelopes and random number simulations. The three parameter compound pdf appears to be flexible enough to represent envelope statistics giving rise to Rayleigh, K, and Nakagami distributions.

Synthesis, Antiinflammatory and Antimicrobial Activity of Some New 1-(3-Phenyl-3,4-Dihydro-2H-1,3-Benzoxazin-6-yl)-Ethanone Derivatives

PubMed Central

Akhter, Mymoona; Husain, A.; Akhter, N.; Khan, M. S. Y

2011-01-01

Synthesis of title compounds (4a-j) was carried out by following aminomethylation Mannich reaction. Test compounds were effective in inhibiting edema induced by carrageenan. The percent inhibition obseved was in the range of 25-83.3%. Compound (4c, e, h and j) were also tested for analgesic effect and showed percent protection ranging between 57-65%. All the synthesized compounds were active against E. coli and S. aureus but only compounds (4 b, c, e, i and j) were active against B. subtilis. All these compound were also found active against A. niger. Compound 4j was the most active compound with 83.3% inhibition of edema, 65.35% percent protection and inhibited all the three bacterial strains. PMID:22131632

Effects of urbanization and long-term rainfall on the occurrence of organic compounds and trace elements in reservoir sediment cores, streambed sediment, and fish tissue from the Santa Ana River basin, California, 1998

USGS Publications Warehouse

Burton, Carmen A.

2002-01-01

Organcochlorine compounds, semivolatile-organic compounds (SVOC), and trace elements were analyzed in reservoir sediment cores, streambed sediment, and fish tissue in the Santa Ana River Basin as part of the U.S. Geological Survey's National Water-Quality Assessment Program. Three reservoirs were sampled in areas that have different degrees of urbanization. Streambed sediment and fish tissue collected at 12 sites were divided into two groups, urban and nonurban. More organochlorine compounds were detected in reservoir sediment cores, streambed sediment and fish tissue, and at higher concentrations at urban sites than at nonurban sites. At all sites, except West Street Basin, concentrations of organochlorine compounds were lower than the probable-effect concentration (PEC). At the highly urbanized West Street Basin, chlordane and p,p'-DDE exceeded the PEC throughout the historical record. The less stringent threshold-effect concentration (TEC) was exceeded for six compounds at eight sites. Most of the organochlorine compounds detected in streambed sediment and fish tissue were at urban sites on the Santa Ana River as opposed to its tributaries, suggesting accumulation and persistence in the river. More SVOCs were detected in reservoir sediment cores and streambed sediment, and at higher concentrations, at urban sites than at nonurban sites. At all the sites, except West Street Basin, concentrations of SVOCs were lower than the PEC. At West Street Basin, chrysene, pyrene, and total polycyclic-aromatic hydrocarbons exceeded the PEC throughout the historical record. The TEC was exceeded for 10 compounds at 3 sites. Most of the SVOCs were detected in streambed sediment at urban sites on tributaries to the Santa Ana River rather than the mainstem itself. The less frequent occurrence and lower concentrations in the Santa Ana River suggest that SVOCs are less persistent than organochlorine compounds, possibly as a result of volatization, gradation, or dilution. Most trace-element detections in reservoir sediment cores and streambed sediment were at urban sites, and the concentrations were generally higher than at nonurban sites. Lead and zinc exceeded their PECs at West Street Basin throughout the historical record; copper exceeded its PEC at Canyon Lake, an area of urban growth. The TEC was exceeded for 10 compounds at 11 sites. Frequency of detection and concentration did not differ between tributary and Santa Ana River sites, which may be attributed to the fact that trace elements occur naturally. Four trace elements (arsenic, copper, mercury, and selenium) had higher concentrations in fish tissue at nonurban sites than at urban sites. Concentrations decreased over time for organochlorine compounds at all three reservoirs, probably a result of the discontinued use of many of the compounds. Decreasing trends in SVOCs and trace elements were observed at West Street Basin, but increasing trends were observed at Canyon Lake. Concentrations of organochlorine compounds, SVOCs, and trace elements were higher during periods of above average rainfall at both West Street Basin and Canyon Lake.

Synthesis of N-formyl-3,4-di-t-butoxycarbonyloxy-6(trimethylstannyl)-L-phenylalanine ethyl ester and its regioselective radiofluorodestannylation to 6-[{sup 18}F]fluoro-1-dopa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Satyamurthy, N.; Barrio, J.R.; Bishop, A.J.

A process is revealed for forming a 6-fluoro derivative of compounds in the L-Dopa family comprising the steps of protecting the groups attached to the benzene ring in the compound followed by serially reacting the protected compound with (a) iodine and silver trifluoroacetic acid; (b) Bb{sub 3}; (c) dit-butyldicarbonate; (d) hexamethyltin; (e) a fluoro compound; (f) hydrobromic acid; and (g) raising the pH to {<=}7. 1 fig.

Synthesis of N-formyl-3,4-di-t-butoxycarbonyloxy-6(trimethylstannyl)-L-phenylalanine ethyl ester and its regioselective radiofluorodestannylation to 6-[{sup 18}F]fluoro-1-dopa

DOEpatents

Satyamurthy, N.; Barrio, J.R.; Bishop, A.J.; Namavari, M.; Bida, G.T.

1996-04-23

A process is revealed for forming a 6-fluoro derivative of compounds in the L-Dopa family comprising the steps of protecting the groups attached to the benzene ring in the compound followed by serially reacting the protected compound with (a) iodine and silver trifluoroacetic acid; (b) Bb{sub 3}; (c) dit-butyldicarbonate; (d) hexamethyltin; (e) a fluoro compound; (f) hydrobromic acid; and (g) raising the pH to {<=}7. 1 fig.

Synthesis of N-formyl-3,4-di-t-butoxycarbonyloxy-6-(trimethylstannyl)-L-phenylalanine ethyl ester and its regioselective radiofluorodestannylation to 6- .sup.18 F!fluoro-1-dopa

DOEpatents

Satyamurthy, Nagichettiar; Barrio, Jorge R.; Bishop, Allyson J.; Namavari, Mohammad; Bida, Gerald T.

1996-01-01

A process for forming a 6-fluoro derivative of compounds in the L-Dopa family comprising the steps of protecting the groups attached to the benzene ring in the compound followed by serially reacting the protected compound with (a) iodine and silver trifluoroacetic acid; (b) Bb.sub.3 ; (c) dit-butyldicarbonate; (d) hexamethyltin; (e) a fluoro compound; (f) hydrobromic acid; and (g) raising the pH to .ltoreq.7.

Persistent Epithelial Defects and Corneal Opacity After Collagen Cross-Linking With Substitution of Dextran (T-500) With Dextran Sulfate in Compounded Topical Riboflavin.

PubMed

Höllhumer, Roland; Watson, Stephanie; Beckingsale, Peter

2017-03-01

Collagen cross-linking (CXL) is a commonly performed procedure to prevent the progression of keratoconus. Riboflavin is an essential part of the procedure, which facilitates both the cross-linking process and protection of intraocular structures. Dextran can be added to riboflavin to create an isotonic solution. This case report highlights the importance of compounding riboflavin with the correct dextran solution. A retrospective case series. Six eyes of 4 male patients with keratoconus aged from 20 to 38 years underwent CXL with substitution of 20% dextran (T-500) with 20% dextran sulfate in a compounded riboflavin 0.1% solution. Postoperatively, persistent corneal epithelial defects, stromal haze, and then scarring occurred. Corneal transplantation was performed for visual rehabilitation but was complicated by graft rejection followed by failure (n = 1 eye), dehiscence (n = 4), cataract (n = 2), post-laser ablation haze (n = 1), and steroid-induced glaucoma (n = 2). The visual outcome was <6/18 in all 6 cases because of irregular astigmatism and stromal haze. Thinning, vascularization, and scarring of the residual host tissue were noted. Substitution of dextran (T-500) with dextran sulfate in riboflavin solutions during CXL results in loss of vision from permanent corneal opacity. Residual host changes may compromise the results of corneal transplantation.

On the use of 31P NMR for the quantification of hydrosoluble phosphorus-containing compounds in coral host tissues and cultured zooxanthellae.

PubMed

Godinot, Claire; Gaysinski, Marc; Thomas, Olivier P; Ferrier-Pagès, Christine; Grover, Renaud

2016-02-23

(31)P Nuclear Magnetic Resonance (NMR) was assessed to investigate the phosphorus-containing compounds present in the tissues of the scleractinian coral Stylophora pistillata as well as of cultured zooxanthellae (CZ). Results showed that phosphorus-containing compounds observed in CZ were mainly phosphate and phosphate esters. Phosphate accounted for 19 ± 2% of the total phosphorus compounds observed in CZ maintained under low P-levels (0.02 μM). Adding 5 mM of dissolved inorganic phosphorus (KH2PO4) to the CZ culture medium led to a 3.1-fold increase in intracellular phosphate, while adding 5 mM of dissolved organic phosphorus led to a reduction in the concentration of phosphorus compounds, including a 2.5-fold intracellular phosphate decrease. In sharp contrast to zooxanthellae, the host mainly contained phosphonates, and to a lesser extent, phosphate esters and phosphate. Two-months of host starvation decreased the phosphate content by 2.4 fold, while bleaching of fed corals did not modify this content. Based on (31)P NMR analyses, this study highlights the importance of phosphonates in the composition of coral host tissues, and illustrates the impact of phosphorus availability on the phosphorus composition of host tissues and CZ, both through feeding of the host and inorganic phosphorus enrichment of the CZ.

On the use of 31P NMR for the quantification of hydrosoluble phosphorus-containing compounds in coral host tissues and cultured zooxanthellae

NASA Astrophysics Data System (ADS)

Godinot, Claire; Gaysinski, Marc; Thomas, Olivier P.; Ferrier-Pagès, Christine; Grover, Renaud

2016-02-01

31P Nuclear Magnetic Resonance (NMR) was assessed to investigate the phosphorus-containing compounds present in the tissues of the scleractinian coral Stylophora pistillata as well as of cultured zooxanthellae (CZ). Results showed that phosphorus-containing compounds observed in CZ were mainly phosphate and phosphate esters. Phosphate accounted for 19 ± 2% of the total phosphorus compounds observed in CZ maintained under low P-levels (0.02 μM). Adding 5 mM of dissolved inorganic phosphorus (KH2PO4) to the CZ culture medium led to a 3.1-fold increase in intracellular phosphate, while adding 5 mM of dissolved organic phosphorus led to a reduction in the concentration of phosphorus compounds, including a 2.5-fold intracellular phosphate decrease. In sharp contrast to zooxanthellae, the host mainly contained phosphonates, and to a lesser extent, phosphate esters and phosphate. Two-months of host starvation decreased the phosphate content by 2.4 fold, while bleaching of fed corals did not modify this content. Based on 31P NMR analyses, this study highlights the importance of phosphonates in the composition of coral host tissues, and illustrates the impact of phosphorus availability on the phosphorus composition of host tissues and CZ, both through feeding of the host and inorganic phosphorus enrichment of the CZ.

On the use of 31P NMR for the quantification of hydrosoluble phosphorus-containing compounds in coral host tissues and cultured zooxanthellae

PubMed Central

Godinot, Claire; Gaysinski, Marc; Thomas, Olivier P.; Ferrier-Pagès, Christine; Grover, Renaud

2016-01-01

31P Nuclear Magnetic Resonance (NMR) was assessed to investigate the phosphorus-containing compounds present in the tissues of the scleractinian coral Stylophora pistillata as well as of cultured zooxanthellae (CZ). Results showed that phosphorus-containing compounds observed in CZ were mainly phosphate and phosphate esters. Phosphate accounted for 19 ± 2% of the total phosphorus compounds observed in CZ maintained under low P-levels (0.02 μM). Adding 5 mM of dissolved inorganic phosphorus (KH2PO4) to the CZ culture medium led to a 3.1-fold increase in intracellular phosphate, while adding 5 mM of dissolved organic phosphorus led to a reduction in the concentration of phosphorus compounds, including a 2.5-fold intracellular phosphate decrease. In sharp contrast to zooxanthellae, the host mainly contained phosphonates, and to a lesser extent, phosphate esters and phosphate. Two-months of host starvation decreased the phosphate content by 2.4 fold, while bleaching of fed corals did not modify this content. Based on 31P NMR analyses, this study highlights the importance of phosphonates in the composition of coral host tissues, and illustrates the impact of phosphorus availability on the phosphorus composition of host tissues and CZ, both through feeding of the host and inorganic phosphorus enrichment of the CZ. PMID:26902733

Alterations in chemically induced tissue injury related to all-trans-retinol pretreatment in rodents.

PubMed

Sauer, J M; Hooser, S B; Badger, D A; Baines, A; Sipes, I G

1995-01-01

Retinol (vitamin A) is an essential nutrient which has many physiological effects throughout the body. Our studies have demonstrated that retinol modulation of immune response, through alteration of macrophage and neutrophil function, can have dramatic effects on the toxicity of some compounds. Based on these studies, our current hypothesis for retinol potentiation of chemical-induced liver injury is that retinol administered to rats prior to the hepatotoxicant (CCl4 and AA in rats; and AA, APAP, and GalN in mice) primes the Kupffer cells to a more active state. This may occur in part as a result of increases in chemical mediators such as TNF from these Kupffer cells. Following hepatocyte damage by a toxicant, Kupffer cells are activated to release reactive oxygen species, immune mediators, and chemotactic factors which all serve to enhance the inflammatory response. This increased inflammatory response then results in increased injury to the already toxicant-damaged hepatocytes. In addition, retinol modulation of toxicant activation and detoxification may also make important contributions to the potentiation of some toxicants such as AA. Retinol protection of CCl4 hepatotoxicity in mice is more difficult to explain at this time but is possibly related to alterations in CCl4 metabolism in this species. Differences in response between pulmonary and liver macrophages (Kupffer cells) may explain the retinol protection from 1-NN pulmonary toxicity. Retinol may decrease the inflammatory response through downregulation of pulmonary macrophage function, thus resulting in decreased pulmonary injury. Finally, since retinol protection of cadmium toxicity in the liver and testis requires 7 days of retinol pretreatment, we suspect that retinol is inducing protective protein(s) in these organs. Aside from its normal biological role in rhe body, clinical medicine has found new uses for retinol in the treatment and prevention of some cancers, and in the treatment of certain dermatologic conditions. Since these patients are frequently administered or exposed to other potentially toxic compounds, it is obviously prudent and necessary to continue research into the effects of retinol on immune modulation and interaction with other compounds. More importantly, these studies demonstrate the modulation of immune function is one mechanism by which one chemical can influence the toxicity of another.

Sustained release of the CCR5 inhibitors CMPD167 and maraviroc from vaginal rings in rhesus macaques.

PubMed

Malcolm, R Karl; Veazey, Ronald S; Geer, Leslie; Lowry, Deborah; Fetherston, Susan M; Murphy, Diarmaid J; Boyd, Peter; Major, Ian; Shattock, Robin J; Klasse, Per Johan; Doyle, Lara A; Rasmussen, Kelsi K; Goldman, Laurie; Ketas, Thomas J; Moore, John P

2012-05-01

Antiretroviral entry inhibitors are now being considered as vaginally administered microbicide candidates for the prevention of the sexual transmission of human immunodeficiency virus. Previous studies testing the entry inhibitors maraviroc and CMPD167 in aqueous gel formulations showed efficacy in the macaque challenge model, although protection was highly dependent on the time period between initial gel application and subsequent challenge. In this paper, we describe the sustained release of maraviroc and CMPD167 from matrix-type silicone elastomer vaginal rings both in vitro and in vivo. Both inhibitors were released continuously during 28 days from rings in vitro at rates of 100 to 2,500 μg/day. In 28-day pharmacokinetic studies in rhesus macaques, the compounds were measured in the vaginal fluid and vaginal tissue; steady-state fluid concentrations were ~10(6)-fold greater than the 50% inhibitory concentrations (IC(50)s) for simian human immunodeficiency virus 162P3 inhibition in macaque lymphocytes in vitro. Plasma concentrations for both compounds were very low. The pretreatment of macaques with Depo-Provera (DP), which is commonly used in macaque challenge studies, was shown to significantly modify the biodistribution of the inhibitors but not the overall amount released. Vaginal fluid and tissue concentrations were significantly decreased while plasma levels increased with DP pretreatment. These observations have implications for designing macaque challenge experiments and also for ring performance during the human female menstrual cycle.

Sustained Release of the CCR5 Inhibitors CMPD167 and Maraviroc from Vaginal Rings in Rhesus Macaques

PubMed Central

Veazey, Ronald S.; Geer, Leslie; Lowry, Deborah; Fetherston, Susan M.; Murphy, Diarmaid J.; Boyd, Peter; Major, Ian; Shattock, Robin J.; Klasse, Per Johan; Doyle, Lara A.; Rasmussen, Kelsi K.; Goldman, Laurie; Ketas, Thomas J.; Moore, John P.

2012-01-01

Antiretroviral entry inhibitors are now being considered as vaginally administered microbicide candidates for the prevention of the sexual transmission of human immunodeficiency virus. Previous studies testing the entry inhibitors maraviroc and CMPD167 in aqueous gel formulations showed efficacy in the macaque challenge model, although protection was highly dependent on the time period between initial gel application and subsequent challenge. In this paper, we describe the sustained release of maraviroc and CMPD167 from matrix-type silicone elastomer vaginal rings both in vitro and in vivo. Both inhibitors were released continuously during 28 days from rings in vitro at rates of 100 to 2,500 μg/day. In 28-day pharmacokinetic studies in rhesus macaques, the compounds were measured in the vaginal fluid and vaginal tissue; steady-state fluid concentrations were ∼106-fold greater than the 50% inhibitory concentrations (IC50s) for simian human immunodeficiency virus 162P3 inhibition in macaque lymphocytes in vitro. Plasma concentrations for both compounds were very low. The pretreatment of macaques with Depo-Provera (DP), which is commonly used in macaque challenge studies, was shown to significantly modify the biodistribution of the inhibitors but not the overall amount released. Vaginal fluid and tissue concentrations were significantly decreased while plasma levels increased with DP pretreatment. These observations have implications for designing macaque challenge experiments and also for ring performance during the human female menstrual cycle. PMID:22330914

Herbal Compound Songyou Yin and Moderate Swimming Suppress Growth and Metastasis of Liver Cancer by Enhancing Immune Function.

PubMed

Zhang, Quan-Bao; Meng, Xiang-Ting; Jia, Qing-An; Bu, Yang; Ren, Zheng-Gang; Zhang, Bo-Heng; Tang, Zhao-You

2016-09-01

Objective Both the Chinese herbal compound Songyou Yin (SYY) and swimming exercise have been shown to have protective effects against liver cancer in animal models. In this study, we investigated whether SYY and moderate swimming (MS) have enhanced effect on suppressing progression of liver cancer by immunomodulation. Methods C57BL/6 mice were transplanted with Hepa1-6 murine liver cancer cell lines and received treatment with SYY alone or SYY combined with MS. The green fluorescent protein (GFP)-positive metastatic foci in lungs were imaged with a stereoscopic fluorescence microscope. Flow cytometry was used to test the proportion of CD4 +, CD8 + T cells in peripheral blood and the proportions of CD4 + CD25 + Foxp3 + Treg cells in peripheral blood, spleen, and tumor tissues. Cytokine transforming growth factor (TGF)-β1 level in serum was detected by ELISA. Results SYY plus MS significantly suppressed the growth and lung metastasis of liver cancer and prolonged survival in tumor-burdened mice. SYY plus MS markedly raised the CD4 to CD8 ratio in peripheral blood and lowered the serum TGF-β1 level and the proportions of Treg cells in peripheral blood, spleen, and tumor tissue. The effects of the combined intervention were significantly superior to SYY or MS alone. Conclusion The combined application of SYY and MS exerted an enhanced effect on suppressing growth and metastasis of liver cancer by strengthening immunity. © The Author(s) 2015.

Concentrations of chlorinated organic compounds in biota and bed sediment in streams of the lower San Joaquin River drainage, California

USGS Publications Warehouse

Brown, Larry R.

1998-01-01

Samples of resident biota and bed sediments were collected in 1992 from 18 sites on or near the floor of the San Joaquin Valley, California, for analysis of 33 organochlorine compounds. The sites were divided into five groups on the basis of physiographic region and land use. Ten compounds were detected in tissue, and 16 compounds were detected in bed sediment. The most frequently detected compound in both media was p,p'-DDE. Concentrations of total DDT (sum of o,p'- and p,p'-forms of DDD, DDE, and DDT) were statistically different among groups of sites for tissue and sediment (Kruskal-Wallis, P < 0.05). Concentrations in both media were highest in streams draining the west side of the valley. Concentrations of total DDT in tissue were significantly correlated with specific conductance, pH, and total alkalinity (P < 0.05), which are indicators of the proportion of irrigation-return flows in stream discharge. Concentrations in sediment on a dry-weight basis were not correlated with these water-quality parameters, but total-organic- carbon (TOC) normalized concentrations were significantly correlated with specific conductance and pH (P < 0.05). Regressions of the concentration of total DDT in tissue as a function of total DDT in bed sediment were significant and explained as much as 76 percent of the variance in the data. The concentration of total DDT in sediment may be related to mechanisms of soil transport to surface water with bioavailability of compounds related to the concentration of TOC in sediment.

Cytoprotective dibenzoylmethane derivatives protect cells from oxidative stress-induced necrotic cell death.

PubMed

Hegedűs, Csaba; Lakatos, Petra; Kiss-Szikszai, Attila; Patonay, Tamás; Gergely, Szabolcs; Gregus, Andrea; Bai, Péter; Haskó, György; Szabó, Éva; Virág, László

2013-06-01

Screening of a small in-house library of 1863 compounds identified 29 compounds that protected Jurkat cells from hydrogen peroxide-induced cytotoxicity. From the cytoprotective compounds eleven proved to possess antioxidant activity (ABTS radical scavenger effect) and two were found to inhibit poly(ADP-ribosyl)ation (PARylation), a cytotoxic pathway operating in severely injured cells. Four cytoprotective dibenzoylmethane (DBM) derivatives were investigated in more detail as they did not scavenge hydrogen peroxide nor did they inhibit PARylation. These compounds protected cells from necrotic cell death while caspase activation, a parameter of apoptotic cell death was not affected. Hydrogen peroxide activated extracellular signal regulated kinase (ERK1/2) and p38 MAP kinases but not c-Jun N-terminal kinase (JNK). The cytoprotective DBMs suppressed the activation of Erk1/2 but not that of p38. Cytoprotection was confirmed in another cell type (A549 lung epithelial cells), indicating that the cytoprotective effect is not cell type specific. In conclusion we identified DBM analogs as a novel class of cytoprotective compounds inhibiting ERK1/2 kinase and protecting from necrotic cell death by a mechanism independent of poly(ADP-ribose) polymerase inhibition. Copyright © 2013 Elsevier Ltd. All rights reserved.

Tetracycline compounds with non-antimicrobial organ protective properties: possible mechanisms of action

PubMed Central

Griffin, Michael O.; Ceballos, Guillermo; Villarreal, Francisco

2010-01-01

Tetracyclines were developed as a result of the screening of soil samples for antibiotics. The firstt of these compounds, chlortetracycline, was introduced in 1947. Tetracyclines were found to be highly effective against various pathogens including rickettsiae, as well as both gram-positive and gram-negative bacteria, thus becoming the first class of broad spectrum antibiotics. Many other interesting properties, unrelated to their antibiotic activity, have been identified for tetracyclines which have led to widely divergent experimental and clinical uses. For example, tetracyclines are also an effective anti-malarial drug. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Another tetracycline, doxycycline is known to exert anti-protease activities. Doxycycline can inhibit matrix metalloproteinases which contribute to tissue destruction activities in diseases such as periodontitis. A large body of literature has provided additional evidence for the “beneficial” actions of tetracyclines, including their ability to act as reactive oxygen species scavengers and anti-inflammatory agents. This review provides a summary of tetracycline’s multiple mechanisms of action as a means to understand their beneficial effects. PMID:20951211

JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage.

PubMed

Becattini, Barbara; Zani, Fabio; Breasson, Ludovic; Sardi, Claudia; D'Agostino, Vito Giuseppe; Choo, Min-Kyung; Provenzani, Alessandro; Park, Jin Mo; Solinas, Giovanni

2016-09-01

Obesity and insulin resistance are associated with oxidative stress, which may be implicated in the progression of obesity-related diseases. The kinase JNK1 has emerged as a promising drug target for the treatment of obesity and type 2 diabetes. JNK1 is also a key mediator of the oxidative stress response, which can promote cell death or survival, depending on the magnitude and context of its activation. In this article, we describe a study in which the long-term effects of JNK1 inactivation on glucose homeostasis and oxidative stress in obese mice were investigated for the first time. Mice lacking JNK1 (JNK1(-/-)) were fed an obesogenic high-fat diet (HFD) for a long period. JNK1(-/-) mice fed an HFD for the long term had reduced expression of antioxidant genes in their skin, more skin oxidative damage, and increased epidermal thickness and inflammation compared with the effects in control wild-type mice. However, we also observed that the protection from obesity, adipose tissue inflammation, steatosis, and insulin resistance, conferred by JNK1 ablation, was sustained over a long period and was paralleled by decreased oxidative damage in fat and liver. We conclude that compounds targeting JNK1 activity in brain and adipose tissue, which do not accumulate in the skin, may be safer and most effective.-Becattini, B., Zani, F., Breasson, L., Sardi, C., D'Agostino, V. G., Choo, M.-K., Provenzani, A., Park, J. M., Solinas, G. JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage. © FASEB.

Identification of an unintended consequence of Nrf2-directed cytoprotection against a key tobacco carcinogen plus a counteracting chemopreventive intervention

PubMed Central

Paonessa, Joseph D.; Ding, Yi; Randall, Kristen L.; Munday, Rex; Argoti, Dayana; Vouros, Paul; Zhang, Yuesheng

2011-01-01

Nrf2 is a major cytoprotective gene and is a key chemopreventive target against cancer and other diseases. Here we show that Nrf2 faces a dilemma in defense against 4-aminobiphenyl (ABP), a major human bladder carcinogen from tobacco smoke and other environmental sources. While Nrf2 protected mouse liver against ABP (which is metabolically activated in liver), the bladder level of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP), the predominant ABP-DNA adduct formed in bladder cells and tissues, was markedly higher in Nrf2+/+ mice than in Nrf2−/− mice after ABP exposure. Notably, Nrf2 protected bladder cells against ABP in vitro. Mechanistic investigations showed that the dichotomous effects of Nrf2 could be explained at least partly by upregulation of UDP-glucuronosyltransferase (UGT). Nrf2 promoted conjugation of ABP with glucuronic acid in the liver, increasing urinary excretion of the conjugate. While glucuronidation of ABP and its metabolites is a detoxification process, these conjugates, which are excreted in urine, are known to be unstable in acidic urine, leading to delivery of the parent compounds to bladder. Hence, while higher liver UGT activity may protect the liver against ABP it increases bladder exposure to ABP. These findings raise concerns of potential bladder toxicity when Nrf2-activating chemopreventive agents are used in humans exposed to ABP, especially in smokers. We further demonstrate that 5,6-dihydrocyclopenta[c][1,2]-dithiole-3(4H)-thione (CPDT) significantly inhibits dG-C8-ABP formation in bladder cells and tissues, but does not appear to significantly modulate ABP-catalyzing UGT in liver. Thus, CPDT exemplifies a counteracting solution to the dilemma posed by Nrf2. PMID:21487034

An Antioxidant Screen Identifies Candidates for Protection of Cochlear Hair Cells from Gentamicin Toxicity

PubMed Central

Noack, Volker; Pak, Kwang; Jalota, Rahul; Kurabi, Arwa; Ryan, Allen F.

2017-01-01

Reactive oxygen species are important elements in ototoxic damage to hair cells (HCs), appearing early in the damage process. Higher levels of natural antioxidants are positively correlated with resistance to ototoxins and many studies have shown that exogenous antioxidants can protect HCs from damage. While a very wide variety of antioxidants with different characteristics and intracellular targets exist, most ototoxicity studies have focused upon one or a few well-characterized compounds. Relatively little research has attempted to determine the comparative efficacy of large variety of different antioxidants. This has been in part due to the lack of translation between cell culture and in vivo measures of efficacy. To circumvent this limitation, we used an in vitro assay based on micro-explants from the basal and middle turns of the neonatal mouse organ of Corti to screen a commercial redox library of diverse antioxidant compounds for their ability to protect mammalian HCs from a high dose of the ototoxic antibiotic gentamicin. The library included several antioxidants that have previously been studied as potential treatments for HC damage, as well as many antioxidants that have never been applied to ototoxicity. The micro-explants were treated with 200 μM gentamicin alone, gentamicin plus one of three dosages of a redox compound, the highest dosage of compound alone, or were untreated. HC counts were determined before the gentamicin insult and at 1, 2, and 3 days afterward to evaluate the HC survival. From a total of 81 antioxidant compounds, 13 exhibited significant protection of HCs. These included members of a variety of antioxidant classes with several novel antioxidants, not previously tested on HCs, appearing to alleviate the damaging gentamicin effect. Some compounds previously shown to be protective of HCs were correspondingly protective in this in vitro screen, while others were not. Finally, one of the three pro-oxidant compounds included in the library as well as six antioxidants exhibited evidence of toxicity in the absence of gentamicin. The results demonstrate the wide variability in the ability of antioxidants to protect HCs from high-dose gentamicin damage, and identify promising candidate leads for further study as potential drug targets. Highlights • A medium-throughput assay based on micro-explants of the organ of Corti was developed to screen mammalian cochlear hair cells for protection from damage by ototoxins. • Eighty one antioxidants and 3 pro-oxidants were evaluated for hair cell protection from high-dose gentamicin. • Thirteen antioxidants were significantly protective, while 6 proved to be damaging. • The use of a common assay permitted an evaluation of the relative capacity of different antioxidants for the protection of hair cells. PMID:28867994

Comparing metabolic effects of six different commercial trivalent chromium compounds.

PubMed

Preuss, Harry G; Echard, Bobby; Perricone, Nicholas V; Bagchi, Debasis; Yasmin, Taharat; Stohs, Sidney J

2008-11-01

Recent reports provide cogent evidence that the average individual becomes chromium deficient with age. Unfortunately, chromium deficiency is strongly associated with many aspects of the Metabolic Syndrome, including insulin resistance and type 2 diabetes. Since replacement of chromium, per os, often ameliorates many deleterious manifestations associated with insulin resistance and diabetes, it is not surprising that many different, commercial trivalent chromium compounds are available on the market. However, previous reports have shown that the form of trivalent chromium (negative charges) can influence effectiveness markedly. We compared various commercial forms of trivalent chromium commonly used alone or in formulations, to examine whether they are equally effective and non-toxic. In the first study, five different chromium products were examined - citrate, amino acid chelate (AAC), chelavite, polynicotinate (NBC), and nicotinate. In the second study, effects of NBC and picolinate were assessed. Results demonstrated that only chelavite and NBC improved insulin sensitivity, and only NBC decreased systolic blood pressure (SBP) significantly. In the second study, both picolinate and NBC significantly decreased SBP compared to control. NBC and picolinate decreased malonyldialdehyde concentrations (free radical formation) and DNA fragmentation in hepatic and renal tissues. No evidence of adverse effects was noted with any of the compounds tested. In conclusion, while all the trivalent chromium compounds tested seem safe, only three enhanced insulin sensitivity (NBC, chelavite, and picolinate) and only two decreased SBP significantly (NBC and picolinate). Furthermore, both NBC and picolinate were protective in lessening free radical formation and DNA damage in the liver and kidneys.

Organic Chemical Concentrations and Reproductive Biomarkers in Common Carp (Cyprinus carpio) Collected from Two Areas in Lake Mead, Nevada, May 1999-May 2000

USGS Publications Warehouse

Goodbred, Steven L.; Leiker, Thomas J.; Patiño, Reynaldo; Jenkins, Jill A.; Denslow, Nancy D.; Orsak, Erik; Rosen, Michael R.

2007-01-01

The U.S. Geological Survey, in cooperation with the U.S. Fish and Wildlife Service, National Park Service, Bureau of Reclamation, and Nevada Department of Wildlife, collected and assessed data to determine the general health and reproductive status of common carp (Cyprinus carpio) at two study areas in Lake Mead, Nevada, during May 1999-May 2000. These data will form the basis of interpretations and provide a comparison for continuing studies on the health of the ecosystem in Lake Mead. One study area, Las Vegas Bay, is in the western part of Lake Mead. Las Vegas Bay receives inflows from Las Vegas Wash, which is predominantly tertiary-treated wastewater effluent, and to a lesser extent stormwater runoff from Las Vegas, Henderson, and other nearby communities, and from ground water underlying Las Vegas Valley. The other study area, Overton Arm, is in the northern extent of Lake Mead. Overton Arm receives inflow from the Virgin and Muddy Rivers, which historically are not influenced by wastewater effluent. Both sexes of common carp were collected bimonthly for 12 months using boat-mounted electrofishing gear (a direct electric current is used to temporarily immobilize fish for capture) to determine their health and reproductive status and any relation between these factors and environmental contaminants. This report presents fish tissue chemistry, organic chemical compound concentrations, and biomarker data for 83 male common carp collected from Las Vegas Bay, similar organic chemistry results for 15 male common carp, and similar biomarker measures for 80 male common carp collected from Overton Arm. Tissue chemistry results also are presented for 16 female common carp and biomarker measures for 79 female common carp collected from Las Vegas Bay, and tissue chemistry results for 15 female common carp and biomarker measures for 81 female common carp collected from Overton Arm. Thirty-three organic chemical compounds plus total concentrations for four groups of compounds (chlordanes, polychlorinated biphenyls [PCBs], brominated diphenyl ethers [BDEs], and triclosans) were analyzed from extracts of whole-body tissue using gas chromatography/mass spectrometry in male common carp from Las Vegas Bay during May 1999 through May 2000. All 33 compounds were detected in at least one sample of whole-body tissue from male common carp collected in Las Vegas Bay. In Overton Arm, 37 organic compounds plus total concentrations of three groups of compounds (PCBs, BDEs, and triclosans) were analyzed in male common carp where 20 (54 percent) of the compounds were detected. Sixteen of the 33 compounds detected in male common carp from Las Vegas Bay and 10 compounds detected in males from Overton Arm have the potential to disrupt the endocrine system in fish in Lake Mead. During May and June 1999, the mean concentration of all organic compounds detected in male common carp was 670 micrograms per kilogram from Las Vegas Bay and 109 micrograms per kilogram from Overton Arm. Twenty-seven organic compounds plus total PCBs were analyzed from extracts of whole-body tissue in female common carp collected in Las Vegas Bay and Overton Arm during May 1999. Twenty-four (86 percent) of these compounds were detected in at least one sample of whole-body tissue from female common carp collected from Las Vegas Bay while 10 (36 percent) chemical compounds were detected in female common carp from Overton Arm during that same period. Median concentrations of all chemical compounds were higher in female common carp from Las Vegas Bay compared to those collected from Overton Arm except Dacthal (DCPA), which was similar between sites. Biomarker measures obtained for male and female common carp include gonadosomatic index (percentage of gonad weight to total body weight), plasma vitellogenin (a phospholipid protein normally produced by female common carp and other oviparous fish), and condition factor [body weight/(fork length)3]. Biomarker measures for male c

Inhibition of Phenylpropanoid Biosynthesis in Artemisia annua L.: A Novel Approach to Reduce Oxidative Browning in Plant Tissue Culture

PubMed Central

Jones, Andrew Maxwell Phineas; Saxena, Praveen Kumar

2013-01-01

Oxidative browning is a common and often severe problem in plant tissue culture systems caused by the accumulation and oxidation of phenolic compounds. The current study was conducted to investigate a novel preventative approach to address this problem by inhibiting the activity of the phenylalanine ammonia lyase enzyme (PAL), thereby reducing the biosynthesis of phenolic compounds. This was accomplished by incorporating 2-aminoindane-2-phosphonic acid (AIP), a competitive PAL inhibitor, into culture media of Artemisia annua as a model system. Addition of AIP into culture media resulted in significant reductions in visual tissue browning, a reduction in total phenol content, as well as absorbance and autoflourescence of tissue extracts. Reduced tissue browning was accompanied with a significant increase in growth on cytokinin based medium. Microscopic observations demonstrated that phenolic compounds accumulated in discrete cells and that these cells were more prevalent in brown tissue. These cells were highly plasmolyzed and often ruptured during examination, demonstrating a mechanism in which phenolics are released into media in this system. These data indicate that inhibiting phenylpropanoid biosynthesis with AIP is an effective approach to reduce tissue browning in A. annua. Additional experiments with Ulmus americana and Acer saccharum indicate this approach is effective in many species and it could have a wide application in systems where oxidative browning restricts the development of biotechnologies. PMID:24116165

Simultaneous Analysis of Anthocyanin and Non-Anthocyanin Flavonoid in Various Tissues of Different Lotus (Nelumbo) Cultivars by HPLC-DAD-ESI-MSn

PubMed Central

Chen, Sha; Xiang, Yue; Deng, Jiao; Liu, Yanling; Li, Shaohua

2013-01-01

A validated HPLC-DAD-ESI-MSn method for the analysis of non-anthocyanin flavonoids was applied to nine different tissues of twelve lotus genotypes of Nelumbo nucifera and N. lutea, together with an optimized anthocyanin extraction and separation protocol for lotus petals. A total of five anthocyanins and twenty non-anthocyanin flavonoids was identified and quantified. Flavonoid contents and compositions varied with cultivar and tissue and were used as a basis to divide tissues into three groups characterized by kaempferol and quercetin derivatives. Influences on flower petal coloration were investigated by principal components analyses. High contents of kaempferol glycosides were detected in the petals of N. nucifera while high quercetin glycoside concentrations occurred in N. lutea. Based on these results, biosynthetic pathways leading to specific compounds in lotus tissues are deduced through metabolomic analysis of different genotypes and tissues and correlations among flavonoid compounds. PMID:23646125

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tatur, I.R.; Prigul`skii, G.B.; Timokhin, I.A.

Enamel paints MS-17 and KhV-110 are used to protect drill bits during transportation and storage. But this requires the surface to be prepared carefully, which is often difficult under production conditions. Some of the promising anticorrosion agents are film-forming inhibited petroleum compounds (FIPC) - materials derived from high-temperature petroleum products blended with corrosion inhibitors and a solvent. Such compounds are used to protect unpainted and painted surfaces; this shortens the preservation process, and generally dispenses which depreservation. Further, they can be used to protect moist, wet, greasy, and rusted surfaces, and concealed inner areas where paint is difficult to apply.more » The purpose of this work was to obtain a film-forming inhibited petroleum compound that has high protective properties, can be applied on unprepared metal surfaces, and meets the following requirements: drill bit protection time during transportation and storage at least 24 months, coat adhesion to the metal at least of force 2, drop point > 90{degrees}C, the material must be applied by pneumatic spraying, in toxicity and inflammability the compound must be of class three, and coat drying time at 60{degrees}C not more than 12 min. The anticorrosion agents are described.« less

The Compound Chinese Medicine “Kang Fu Ling” Protects against High Power Microwave-Induced Myocardial Injury

PubMed Central

Zhang, Xueyan; Gao, Yabing; Dong, Ji; Wang, Shuiming; Yao, Binwei; Zhang, Jing; Hu, Shaohua; Xu, Xinping; Zuo, Hongyan; Wang, Lifeng; Zhou, Hongmei; Zhao, Li; Peng, Ruiyun

2014-01-01

Background The prevention and treatment of Microwave-caused cardiovascular injury remains elusive. This study investigated the cardiovascular protective effects of compound Chinese medicine “Kang Fu Ling” (KFL) against high power microwave (HPM)-induced myocardial injury and the role of the mitochondrial permeability transition pore (mPTP) opening in KFL protection. Methods Male Wistar rats (100) were divided into 5 equal groups: no treatment, radiation only, or radiation followed by treatment with KFL at 0.75, 1.5, or 3 g/kg/day. Electrocardiography was used to Electrophysiological examination. Histological and ultrastructural changes in heart tissue and isolated mitochondria were observed by light microscope and electron microscopy. mPTP opening and mitochondrial membrane potential were detected by confocal laser scanning microscopy and fluorescence analysis. Connexin-43 (Cx-43) and endothelial nitric oxide synthase (eNOS) were detected by immunohistochemistry. The expression of voltage-dependent anion channel (VDAC) was detected by western blotting. Results At 7 days after radiation, rats without KFL treatment showed a significantly lower heart rate (P<0.01) than untreated controls and a J point shift. Myocyte swelling and rearrangement were evident. Mitochondria exhibited rupture, and decreased fluorescence intensity, suggesting opening of mPTP and a consequent reduction in mitochondrial membrane potential. After treatment with 1.5 g/kg/day KFL for 7 d, the heart rate increased significantly (P<0.01), and the J point shift was reduced flavorfully (P<0.05) compared to untreated, irradiated rats; myocytes and mitochondria were of normal morphology. The fluorescence intensities of dye-treated mitochondria were also increased, suggesting inhibition of mPTP opening and preservation of the mitochondrial membrane potential. The microwave-induced decrease of Cx-43 and VDAC protein expression was significantly reversed. Conclusion Microwave radiation can cause electrophysiological, histological and ultrastructural changes in the heart. KFL at 1.5 g/kg/day had the greatest protective effect on these cardiovascular events. mPTP plays an important role in the protective effects of KFL against microwave-radiation-induced myocardial injury. PMID:24992449

Mycosporine and mycosporine-like amino acids: A paramount tool against ultra violet irradiation

PubMed Central

Bhatia, Saurabh; Garg, Arun; Sharma, K.; Kumar, S.; Sharma, A.; Purohit, A. P.

2011-01-01

Various facts demonstrated that UVB is harmful to organisms. Sunscreen compounds are usually used to prevent the excessive damage caused by UVB. However, certain photosynthetic organisms have evolved mechanisms to counteract the toxicity of ultraviolet radiation by synthesizing UV screening compounds such as mycosporine-like amino acids (MAAs). MAAs provide UV protection to primary and secondary consumers through food chain and to non-biological materials by photostabilizing action. Information related to the ecological consequence of MAAs and their spatial distribution from a wide range of organisms is accumulating. Hence, our studies seek a potent class of natural sun protective compounds to understand their relationship with environment and to develop a protocol for large-scale industrial production of these compounds so that they can find application as UV-protecting cosmetics. PMID:22279371

Discriminating model for diagnosis of basal cell carcinoma and melanoma in vitro based on the Raman spectra of selected biochemicals

NASA Astrophysics Data System (ADS)

Silveira, Landulfo; Silveira, Fabrício Luiz; Bodanese, Benito; Zângaro, Renato Amaro; Pacheco, Marcos Tadeu T.

2012-07-01

Raman spectroscopy has been employed to identify differences in the biochemical constitution of malignant [basal cell carcinoma (BCC) and melanoma (MEL)] cells compared to normal skin tissues, with the goal of skin cancer diagnosis. We collected Raman spectra from compounds such as proteins, lipids, and nucleic acids, which are expected to be represented in human skin spectra, and developed a linear least-squares fitting model to estimate the contributions of these compounds to the tissue spectra. We used a set of 145 spectra from biopsy fragments of normal (30 spectra), BCC (96 spectra), and MEL (19 spectra) skin tissues, collected using a near-infrared Raman spectrometer (830 nm, 50 to 200 mW, and 20 s exposure time) coupled to a Raman probe. We applied the best-fitting model to the spectra of biochemicals and tissues, hypothesizing that the relative spectral contribution of each compound to the tissue Raman spectrum changes according to the disease. We verified that actin, collagen, elastin, and triolein were the most important biochemicals representing the spectral features of skin tissues. A classification model applied to the relative contribution of collagen III, elastin, and melanin using Euclidean distance as a discriminator could differentiate normal from BCC and MEL.

Solvent Separating Secondary Metabolites Directly from Biosynthetic Tissue for Surface-Assisted Laser Desorption Ionisation Mass Spectrometry

PubMed Central

Rudd, David; Benkendorff, Kirsten; Voelcker, Nicolas H.

2015-01-01

Marine bioactive metabolites are often heterogeneously expressed in tissues both spatially and over time. Therefore, traditional solvent extraction methods benefit from an understanding of the in situ sites of biosynthesis and storage to deal with heterogeneity and maximize yield. Recently, surface-assisted mass spectrometry (MS) methods namely nanostructure-assisted laser desorption ionisation (NALDI) and desorption ionisation on porous silicon (DIOS) surfaces have been developed to enable the direct detection of low molecular weight metabolites. Since direct tissue NALDI-MS or DIOS-MS produce complex spectra due to the wide variety of other metabolites and fragments present in the low mass range, we report here the use of “on surface” solvent separation directly from mollusc tissue onto nanostructured surfaces for MS analysis, as a mechanism for simplifying data annotation and detecting possible artefacts from compound delocalization during the preparative steps. Water, ethanol, chloroform and hexane selectively extracted a range of choline esters, brominated indoles and lipids from Dicathais orbita hypobranchial tissue imprints. These compounds could be quantified on the nanostructured surfaces by comparison to standard curves generated from the pure compounds. Surface-assisted MS could have broad utility for detecting a broad range of secondary metabolites in complex marine tissue samples. PMID:25786067

Evaluation of protective effect of different dietary fibers on polyphenolic profile stability of maqui berry (Aristotelia chilensis (Molina) Stuntz) during in vitro gastrointestinal digestion.

PubMed

Viuda-Martos, Manuel; Lucas-Gonzalez, Raquel; Ballester-Costa, Carmen; Pérez-Álvarez, José A; Muñoz, Loreto A; Fernández-López, Juana

2018-01-24

The aim of this work was to determine the protective effect of different dietary fibers on (i) the recovery and bioaccessibility indexes, and (ii) the stability of polyphenolic compounds (phenolic acids, flavonoids and anthocyanins) of maqui berry powder subjected to in vitro gastrointestinal digestion (GID). The extracts obtained in each phase (oral, gastric and intestinal) of GID were used to analyze the stability of polyphenolic compounds by HPLC, and the bioaccessibility of these compounds was also determined. At the end of the GID process, the mixture of maqui berry with the different fibers increased the bioaccessibility index of the phenolic and flavonoid compounds in all cases. The results obtained suggest that the anthocyanins and phenolic acids and flavonoid compounds present in maqui are stabilized through dietary fiber interactions, which might provide sufficient levels for absorption during gastrointestinal digestion. The gums sodium carboxymethyl cellulose, xanthan gum and guar gum provided the best protective effect.

Multifactorial antimicrobial wood protectants

Treesearch

Robert D. Coleman; Carol A. Clausen

2008-01-01

It is unlikely that a single antimicrobial compound, whether synthetic or natural, will provide the ‘magic bullet’ for eliminating multiple biological agents affecting wood products. Development of synergistic combinations of selected compounds, especially those derived from natural sources, is recognized as a promising approach to improved wood protection. Recent...

MEASUREMENT OF VOLATILE ORGANIC COMPOUNDS BY THE US ENVIRONMENTAL PROTECTION AGENCY COMPENDIUM METHOD TO-17 - EVALUATION OF PERFORMANCE CRITERIA

EPA Science Inventory

An evaluation of performance criteria for US Environmental Protection Agency Compendium Method TO-17 for monitoring volatile organic compounds (VOCs) in air has been accomplished. The method is a solid adsorbent-based sampling and analytical procedure including performance crit...

Carbon limitation reveals allocation priority to defense compounds in peppermint

NASA Astrophysics Data System (ADS)

Forkelova, Lenka; Unsicker, Sybille; Forkel, Matthias; Huang, Jianbei; Trumbore, Susan; Hartmann, Henrik

2016-04-01

Studies of carbon partitioning during insect or pathogen infestation reveal high carbon investment into induced chemical defenses to deter the biotic agent (Baldwin, 1998). However, little is known how carbon investment into chemical defenses changes under abiotic stress such as drought. Drought forces plants to close their stomata to prevent water loss through transpiration while decreasing the amount of assimilated carbon. Furthermore drought hampers carbohydrates translocation due to declining plant hydration and reduced phloem functioning (McDowell, 2011; Hartmann et al., 2013; Sevanto, 2014). Hence long lasting drought can force plants into carbon starvation. The aim of our study was to disentangle carbon allocation priorities between growth, maintenance metabolism, storage and production of defense compounds under carbon limiting conditions using peppermint as our model plant. Drought is not the only method how to manipulate plant carbon metabolism and photosynthetic yield. Exposing plants to reduced [CO2] air is a promising tool simulating drought induced carbon limitation without affecting phloem functioning and so carbohydrate translocation (Hartmann et al., 2015). We exposed peppermint plants to drought (50% of the control irrigation) and to low [CO2] (progressive decrease from 350 ppm to 20 ppm) to disentangle hydraulic failure from carbon starvation effects on carbon allocation. Drought was applied as a cross-treatment yielding four treatments: watered and high [CO2] (W+CO2), drought and high [CO2] (D+CO2), water and low [CO2] (W-CO2), drought and low [CO2] (D-CO2). We analyzed the most abundant terpenoid defense compounds (α-Pinene, sabinene, myrcene, limonene, menthone, menthol and pulegone) and used continuous 13CO2 labelling to trace allocation pattern of new and old assimilated carbon in the four carbon sinks (structural biomass, water soluble sugars, starch and terpenoid defense compounds) in young expanding leaf tissue. This leaf tissue grew after the start of treatments and after the onset of the 13CO2 labelling. Under the control treatment (W+CO2) the relative proportion of new carbon in the four carbon sinks was very similar whereas under the three stress treatments (D+CO2, W-CO2, D-CO2) new carbon was preferentially invested into terpenoid defense compounds. This indicates that also under abiotic stress plants need to invest carbon into defense and so protect immature leaf tissue to secure long-term photosynthetic activity (Massad et al., 2014). Even though the concentration of water soluble sugars under both low [CO2] treatments dramatically dropped, concentration of terpenoid compounds correspondingly change only under the combination of drought and low [CO2] (D-CO2), which was the harshest treatment. Drought alone (D+CO2) caused high investment of old carbon and concentration increase of water soluble sugars as well as starch compared to other treatments. This carbohydrates increase could be explained by the use of water soluble sugars as osmoprotectants (Dichio et al.,2009) and by the fast growth decline as the main carbon sink (Muller et al., 2011).

A quantitative multiplex nuclease protection assay reveals immunotoxicity gene expression profiles in the rabbit model for vaginal drug safety evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fichorova, Raina N., E-mail: rfichorova@rics.bwh.harvard.edu; Mendonca, Kevin; Yamamoto, Hidemi S.

Any vaginal product that alters the mucosal environment and impairs the immune barrier increases the risk of sexually transmitted infections, especially HIV infection, which thrives on mucosal damage and inflammation. The FDA-recommended rabbit vaginal irritation (RVI) model serves as a first line selection tool for vaginal products; however, for decades it has been limited to histopathology scoring, insufficient to select safe anti-HIV microbicides. In this study we incorporate to the RVI model a novel quantitative nuclease protection assay (qNPA) to quantify mRNA levels of 25 genes representing leukocyte differentiation markers, toll-like receptors (TLR), cytokines, chemokines, epithelial repair, microbicidal and vascularmore » markers, by designing two multiplex arrays. Tissue sections were obtained from 36 rabbits (6 per treatment arm) after 14 daily applications of a placebo gel, saline, 4% nonoxynol-9 (N-9), and three combinations of the anti-HIV microbicides tenofovir (TFV) and UC781 in escalating concentrations (highest: 10% TFV + 2.5%UC781). Results showed that increased expression levels of toll-like receptor (TLR)-4, interleukin (IL)-1β, CXCL8, epithelial membrane protein (EMP)-1 (P < 0.05), and decreased levels of TLR2 (P < 0.05), TLR3 and bactericidal permeability increasing protein (BPI) (P < 0.001) were associated with cervicovaginal mucosal alteration (histopathology). Seven markers showed a significant linear trend predicting epithelial damage (up with CD4, IL-1β, CXCL8, CCL2, CCL21, EMP1 and down with BPI). Despite the low tissue damage RVI scores, the high-dose microbicide combination gel caused activation of HIV host cells (SLC and CD4) while N-9 caused proinflammatory gene upregulation (IL-8 and TLR4) suggesting a potential for increasing risk of HIV via different mechanisms depending on the chemical nature of the test product. - Highlights: • A transcriptome nuclease protection assay assessed microbicides for vaginal safety. • Biomarkers were correlated with histopathology in paraffin-embedded rabbit tissues. • Compounds differed by effects on putative pathways of increased risk of HIV. • Nonsoxynol-9 caused inflammatory tissue damage involving TLR4 and IL-8. • An antiretroviral combination stimulated immune cells evidenced by SLC and CD4.« less

The toxicity of vanadium on gastrointestinal, urinary and reproductive system, and its influence on fertility and fetuses malformations.

PubMed

Wilk, Aleksandra; Szypulska-Koziarska, Dagmara; Wiszniewska, Barbara

2017-09-25

Vanadium is a transition metal that has a unique and beneficial effect on both humans and animals. For many years, studies have suggested that vanadium is an essential trace element. Its biological properties are of interest due to its therapeutic potential, including in the treatment of diabetes mellitus. Vanadium deficiencies can lead to a range of pathologies. However, excessive concentration of this metal can cause irreversible damage to various tissues and organs. Vanadium toxicity mainly manifests in gastrointestinal symptoms, including diarrhea, vomiting, and weight reduction. Vanadium also exhibits hepatotoxic and nephrotoxic properties, including glomerulonephritis and pyelonephritis. Vanadium compounds may also lead to partial degeneration of the seminiferous epithelium of the seminiferous tubules in the testes and can affect male fertility. This paper describes the harmful effects of vanadium on the morphology and physiology of both animal and human tissues, including the digestive system, the urinary tract, and the reproductive system. What is more, the following study includes data concerning the correlation between the above-mentioned metal and its influence on fertility and fetus malformations. Additionally, this research identifies the doses of vanadium which lead to pathological alterations becoming visible within tissues. Moreover, this study includes information about the protective efficacy of some substances in view of the toxicity of vanadium.

Chondro-Protective and Antiarthritic Effects of Sulfonamido-Based Gallate-ZXHA-TC in Vitro and in Vivo.

PubMed

Lu, Zhenhui; Wu, Huayu; Lin, Xiao; Liu, Buming; Lin, Cuiwu; Zheng, Li; Zhao, Jinmin

2016-06-17

The effects of gallic acid (GA) on arthritis are limited by weak antioxidant effects and inferior biological properties of GA. We recently described a new series of synthesized GA derivatives by coupling with sulfonamides. Among these analogs, a novel compound synthesized from GA and sulfadimoxine (SDM) named ZXHA-TC exhibited the most robust anti-inflammatory potential. In this current study, the chondro-protective and antiarthritic effects of ZXHA-TC were investigated both in vitro and in vivo. In the in vitro study, ZXHA-TC exerted chondro-protective effects as evidenced by promoting cell proliferation and the maintaining of the phenotype of articular chondrocytes treated with interleukin-1-beta (IL-1β). The potential of ZXHA-TC to slow the progress of osteoarthritis (OA) was suggested by a reduction in matrix metalloproteinases (MMPs) and the up-regulation of the tissue inhibitor of metalloproteinase-1 (TIMP-1). In a rabbit anterior cruciate ligament transaction (ACLT) model of OA, ZXHA-TC exerted a protective effect on arthritis as assessed by macroscopic scores, histological, qRT-PCR, and immunohistochemical analyses. The effects of ZXHA-TC on inhibiting the production of inflammatory mediators in OA may be mediated partly by the suppression of the PI3K/AKT pathway or MAPK cascades, leading to NF-κB inactivation. Thus, this study indicates that ZXHA-TC may be developed as a potential therapeutic agent for OA.

Djulis (Chenopodium formosanum Koidz.) Water Extract and Its Bioactive Components Ameliorate Dermal Damage in UVB-Irradiated Skin Models

PubMed Central

Huang, Ya-Ling; Liu, Yao-Cheng; Tsai, Pi-Jen

2016-01-01

Dermal photoaging is a condition of skin suffering inappropriate ultraviolet (UV) exposure and exerts inflammation, tissue alterations, redness, swelling, and uncomfortable feelings. Djulis (Chenopodium formosanum Koidz.) is a cereal food and its antioxidant and pigment constituents may provide skin protection from photoaging, but it still lacks proved experiments. In this study, protective effects of djulis extract (CFE) on UVB-irradiated skin were explored. The results showed that HaCaT cells with 150 μg/mL CFE treatment had higher survival and less production of interleukin- (IL-) 6, matrix metalloprotease- (MMP-) 1, and reactive oxygen species (ROS) in UVB-irradiated conditions. Subsequently, in animal studies, mice supplemented with CFE (100 mg/kg BW) were under UVB irradiation and had thinner epidermis and lower IL-6 levels in skin layer. These data demonstrate that bioactive compounds possessing the potency of antiphotoaging exist in CFE. Following that, we found rutin and chlorogenic acid (10–100 μM) could significantly increase cell viability and decrease the production of IL-6 in UVB models. Additionally, djulis pigment-betanin has no effect of increasing cell viability in this study. Our findings suggest CFE can protect skin against UV-induced damage and this protection is mainly from contributions of rutin and chlorogenic acid. PMID:27847821

Selective Shielding of Bone Marrow: An Approach to Protecting Humans from External Gamma Radiation.

PubMed

Waterman, Gideon; Kase, Kenneth; Orion, Itzhak; Broisman, Andrey; Milstein, Oren

2017-09-01

The current feasibility of protecting emergency responders through bone marrow selective shielding is highlighted in the recent OECD/NEA report on severe accident management. Until recently, there was no effective personal protection from externally penetrating gamma radiation. In Chernobyl, first-responders wore makeshift lead sheeting, whereas in Fukushima protective equipment from gamma radiation was not available. Older protective solutions that use thin layers of shielding over large body surfaces are ineffective for energetic gamma radiation. Acute exposures may result in Acute Radiation Syndrome where the survival-limiting factor up to 10 Gy uniform, homogeneous exposure is irreversible bone marrow damage. Protracted, lower exposures may result in malignancies of which bone marrow is especially susceptible, being compounded by leukemia's short latency time. This highlights the importance of shielding bone marrow for preventing both deterministic and stochastic effects. Due to the extraordinary regenerative potential of hematopoietic stem cells, to effectively prevent the deterministic effects of bone marrow exposure, it is sufficient to protect only a small fraction of this tissue. This biological principle allows for a new class of equipment providing unprecedented attenuation of radiation to select marrow-rich regions, deferring the hematopoietic sub-syndrome of Acute Radiation Syndrome to much higher doses. As approximately half of the body's active bone marrow resides within the pelvis region, shielding this area holds great promise for preventing the deterministic effects of bone marrow exposure and concomitantly reducing stochastic effects. The efficacy of a device that selectively shields this region and other radiosensitive organs in the abdominal area is shown here.

Hydroxamic acid content and toxicity of rye at selected growth stages.

PubMed

Rice, Clifford P; Park, Yong Bong; Adam, Frédérick; Abdul-Baki, Aref A; Teasdale, John R

2005-08-01

Rye (Secale cereale L.) is an important cover crop that provides many benefits to cropping systems including weed and pest suppression resulting from allelopathic substances. Hydroxamic acids have been identified as allelopathic compounds in rye. This research was conducted to improve the methodology for quantifying hydroxamic acids and to determine the relationship between hydroxamic acid content and phytotoxicity of extracts of rye root and shoot tissue harvested at selected growth stages. Detection limits for an LC/MS-MS method for analysis of hydroxamic acids from crude aqueous extracts were better than have been reported previously. (2R)-2-beta-D-Glucopyranosyloxy-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one (DIBOA-G), 2,4-dihydroxy-(2H)-1,4-benzoxazin-3(4H)-one (DIBOA), benzoxazolin-2(3H)-one (BOA), and the methoxy-substituted form of these compounds, (2R)-2-beta-D-glucopyranosyloxy-4-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA glucose), 2,4-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA), and 6-methoxy-benzoxazolin-2(3H)-one (MBOA), were all detected in rye tissue. DIBOA and BOA were prevalent in shoot tissue, whereas the methoxy-substituted compounds, DIMBOA glucose and MBOA, were prevalent in root tissue. Total hydroxamic acid concentration in rye tissue generally declined with age. Aqueous crude extracts of rye shoot tissue were more toxic than extracts of root tissue to lettuce (Lactuca sativa L.) and tomato (Lycopersicon esculentum Mill.) root length. Extracts of rye seedlings (Feekes growth stage 2) were most phytotoxic, but there was no pattern to the phytotoxicity of extracts of rye sampled at growth stages 4 to 10.5.4, and no correlation of hydroxamic acid content and phytotoxicity (I50 values). Analysis of dose-response model slope coefficients indicated a lack of parallelism among models for rye extracts from different growth stages, suggesting that phytotoxicity may be attributed to compounds with different modes of action at different stages. Hydroxamic acids may account for the phytoxicity of extracts derived from rye at early growth stages, but other compounds are probably responsible in later growth stages.

Method for sampling and analysis of volatile biomarkers in process gas from aerobic digestion of poultry carcasses using time-weighted average SPME and GC-MS.

PubMed

Koziel, Jacek A; Nguyen, Lam T; Glanville, Thomas D; Ahn, Heekwon; Frana, Timothy S; Hans van Leeuwen, J

2017-10-01

A passive sampling method, using retracted solid-phase microextraction (SPME) - gas chromatography-mass spectrometry and time-weighted averaging, was developed and validated for tracking marker volatile organic compounds (VOCs) emitted during aerobic digestion of biohazardous animal tissue. The retracted SPME configuration protects the fragile fiber from buffeting by the process gas stream, and it requires less equipment and is potentially more biosecure than conventional active sampling methods. VOC concentrations predicted via a model based on Fick's first law of diffusion were within 6.6-12.3% of experimentally controlled values after accounting for VOC adsorption to the SPME fiber housing. Method detection limits for five marker VOCs ranged from 0.70 to 8.44ppbv and were statistically equivalent (p>0.05) to those for active sorbent-tube-based sampling. The sampling time of 30min and fiber retraction of 5mm were found to be optimal for the tissue digestion process. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of different products of peach (Prunus persica L. Batsch) from a variety developed in southern Brazil on oxidative stress and inflammatory parameters in vitro and ex vivo

PubMed Central

Gasparotto, Juciano; Somensi, Nauana; Bortolin, Rafael Calixto; Moresco, Karla Suzana; Girardi, Carolina Saibro; Klafke, Karina; Rabelo, Thallita Kelly; Morrone, Maurilio Da Silva; Vizzotto, Márcia; Raseira, Maria do Carmo Bassols; Moreira, José Claudio Fonseca; Gelain, Daniel Pens

2014-01-01

Antioxidant, anti-glycation and anti-inflammatory activities of fresh and conserved peach fruits (Prunus persica L. Batsch) were compared. Fresh peach pulps, peels, preserve peach pulps and the preserve syrup were prepared at equal concentrations. Rat liver, kidney and brain cortex tissue slices were pre-incubated with peach samples, subjected to oxidative stress with FeSO4 and hydrogen peroxide. Fresh peach pulps and peel conferred higher protection against cytotoxicity and oxidative stress than preserve peach pulps in most tissues. Release of tumor necrosis factor-α and interleukin-1β was also significantly decreased by Fresh peach pulps and peel, followed by preserve peach pulps. Total phenolic determination and HPLC analysis of carotenoids showed that the content of secondary metabolites in Fresh peach pulps and peel is significantly higher than in preserve peach pulps, while the syrup had only small or trace amounts of these compounds. Fresh peach pulps and Peel demonstrated high antioxidant and anti-inflammatory effects preventing against induced damage. PMID:25320458

Direct effects of manganese compounds on dopamine and its metabolite Dopac: an in vitro study

PubMed Central

Sistrunk, Shannon C.; Ross, Matthew K.; Filipov, Nikolay M.

2007-01-01

Following combustion of fuel containing the additive methylcyclopentadienyl-manganese-tricarbonyl (MMT), manganese phosphate (MnPO4) and manganese sulfate (MnSO4) are emitted in the atmosphere. Manganese chloride (MnCl2), another Mn2+ species, is widely used experimentally. Using rat striatal slices, we found that MnPO4 decreased tissue and media dopamine (DA) and media Dopac (a DA metabolite) levels substantially more than either MnCl2 or MnSO4; antioxidants were partially protective. Also, both MnCl2 and MnPO4 (more potently) oxidized DA and Dopac even in the absence of tissue in the media, suggesting a direct interaction between Mn and DA/Dopac. Because aminochrome is a major oxidation product of DA, we next determined whether MnPO4 will be more potent in forming aminochrome than MnCl2 or MnSO4 which, indeed, was the case. Thus, a potential additional mechanism for the neurotoxic effects of environmentally-relevant forms of Mn, MnPO4 in particular, is the generation of reactive DA intermediates. PMID:18449324

Thyroid status modulates glycoxidative and lipoxidative modification of tissue proteins.

PubMed

Pamplona, R; Portero-Otín, M; Ruiz, C; Bellmunt, M J; Requena, J R; Thorpe, S R; Baynes, J W; Romero, M; López-Torres, M; Barja, G

1999-10-01

Steady state protein modification by carbonyl compounds is related to the rate of carbonyl adduct formation and the half-life of the protein. Thyroid hormones are physiologic modulators of both tissue oxidative stress and protein degradation. The levels of the glycation product N(epsilon)-fructoselysine (FL) and those of the oxidation products, N(epsilon)-(carboxymethyl)lysine (CML) and malondialdehyde-lysine (MDA-lys), identified by GC/MS in liver proteins, decreased significantly in hyperthyroid rats, as well as (less acutely) in hypothyroid animals. Immunoblotting of liver proteins for advanced glycation end-products (AGE) is in agreement with the results obtained by GC/MS. Cytosolic proteolytic activity against carboxymethylated foreign proteins measured in vitro was significantly increased in hypo- and hyperthyroidism. Oxidative damage to DNA, estimated as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodG), did not show significant differences between groups. The results suggests that the steady state levels of these markers depend on the levels of thyroid hormones, presumably through their combined effects on the rates of protein degradation and oxidative stress, whereas DNA is more protected from oxidative damage.

Signs of antimetastatic activity of palladium complexes of methylenediphosphonic acid in IR spectra

NASA Astrophysics Data System (ADS)

Tolstorozhev, G. B.; Skornyakov, I. V.; Pekhnio, V. I.; Kozachkova, A. N.; Sharykina, N. I.

2012-07-01

We have used Fourier transform IR spectroscopy methods to study normal mouse lung tissue and also after subcutaneous transplantation of a B-16 melanoma tumor in the tissue. We also studied tissues with B-16 melanoma after they were treated with coordination compounds based on palladium complexes of methylenediphosphonic acid. The IR spectra of the lung tissues with metastases in the region of the C = O stretching vibrations are different from the IR spectra of normal tissue. We identified spectroscopic signs of the presence of metastases in the lung. We show that when a cancerous tumor is treated with a preparation of palladium complexes of methylenediphosphonic acid, the spectroscopic signs of the presence of metastases in the lung are missing. After treatment with the optimal dose of this drug, the IR spectrum of the lung tissue in which multiple metastases were present before treatment corresponds to the spectrum of normal tissue. We have determined the efficacy of the antitumor activity of coordination compounds based on palladium complexes of methylenediphosphonic acid.

Environmental Chemicals Modulate Polar Bear (Ursus maritimus) Peroxisome Proliferator-Activated Receptor Gamma (PPARG) and Adipogenesis in Vitro.

PubMed

Routti, Heli; Lille-Langøy, Roger; Berg, Mari K; Fink, Trine; Harju, Mikael; Kristiansen, Kurt; Rostkowski, Pawel; Rusten, Marte; Sylte, Ingebrigt; Øygarden, Lene; Goksøyr, Anders

2016-10-04

We studied interactions between polar bear peroxisome proliferator-activated receptor gamma (pbPPARG) and selected compounds using a luciferase reporter assay and predictions through molecular docking. Furthermore, we studied adipogenesis by liver and adipose tissue extracts from a polar bear and three synthetic mixtures of contaminants in murine 3T3-L1 preadipocytes and polar bear adipose tissue-derived stem cells (pbASCs). PCB153 and p,p'-DDE antagonized pbPPARG, although their predicted receptor-ligand affinity was weak. PBDEs, tetrabromobisphenol A, and PCB170 had a weak agonistic effect on pbPPARG, while hexabromocyclododecane, bisphenol A, oxychlordane, and endosulfan were weak antagonists. pbPPARG-mediated luciferase activity was suppressed by synthetic contaminant mixtures reflecting levels measured in polar bear adipose tissue, as were transcript levels of PPARG and the PPARG target gene fatty acid binding protein 4 (FABP4) in pbASCs. Contaminant extracts from polar bear tissues enhanced triglyceride accumulation in murine 3T3-L1 cells and pbASCs, whereas triglyceride accumulation was not affected by the synthetic mixtures. Chemical characterization of extracts using nontarget methods revealed presence of exogenous compounds that have previously been reported to induce adipogenesis. These compounds included phthalates, tonalide, and nonylphenol. In conclusion, major legacy contaminants in polar bear adipose tissue exert antagonistic effects on PPARG, but adipogenesis by a mixture containing emerging compounds may be enhanced through PPARG or other pathways.

Characterization and inhibition studies of tissue nonspecific alkaline phosphatase by aminoalkanol derivatives of 1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5,10-trione, new competitive and non-competitive inhibitors, by capillary electrophoresis.

PubMed

Grodner, Błażej; Napiórkowska, Mariola

2017-09-05

The article describes the inhibitory effect of two new aminoalkanol derivatives on the enzymatic kinetic of tissue non-specific alkaline phosphatase with use of capillary zone electrophoresis to evaluate the inhibitory effect. This technique allows to investigate of the enzymatic kinetic by the measure of the amounts of the substrate and product in the presence of compound (I) or (II) in the reaction mixture. The separation process was conducted using an eCAP fused-silica capillary. The detector was set at 200nm. The best parameters for the analysis were: 25mM sodium dihydrogen phosphate adjusted to pH=2.5, temperature 25°C, and voltage -15kV. Lineweaver-Burk plots were constructed and determined by comparison of the Km, of alkaline phosphatase in the presence of inhibitor (I) or (II) with the Km in a solution without inhibitor. The influence of replacement the propylamine group by the dimethylamine group on tissue non-specific alkaline phosphatase inhibition activity of new derivatives (I) and (II) was investigated. The tested compounds (I) and (II) were found to be tissue non-specific alkaline phosphatase inhibitors. Detailed kinetic studies indicated a competitive mode of inhibition against tissue non-specific alkaline phosphatase for compound (I) and non-competitive mode of inhibition for compound (II). Copyright © 2017 Elsevier B.V. All rights reserved.

A descriptive study to provide evidence of the teratogenic and cellular effects of sibutramine and ephedrine on cardiac- and liver-tissue of chick embryos.

PubMed

Oberholzer, Hester Magdalena; Van Der Schoor, Ciska; Taute, Helena; Bester, Megan Jean

2015-08-01

Exposure to drugs during pregnancy is a major concern, as some teratogenic compounds can influence normal foetal development. Although the use of drugs during pregnancy should generally be avoided, exposure of the developing foetus to teratogens may occur unknowingly since these compounds may be hidden in products that are being marketed as "all natural." The aim of the current study was to investigate the possible teratogenic and cellular effects of sibutramine-a serotonin-norepinephrine reuptake inhibitor used in the treatment of obesity-on the heart and liver tissue of chick embryos. Ephedrine was used as a positive control. The chick embryo model was chosen because it has been used in studying developmental and experimental biology and teratology with great success. The embryos were exposed to three different concentrations of sibutramine and ephedrine respectively. The results obtained revealed that both compounds exhibited embryotoxicity when compared to the control groups. Liver and heart tissue of the exposed embryos was severely affected by these compounds in a dose-related manner. Morphology similar to that of muscle dystrophy was observed in the heart, where the muscle tissue was infiltrated by adipose and connective tissue. Severe liver steatosis was also noted. A more in-depth investigation into the molecular pathways involved might provide more information on the exact mechanism of toxicity of these products influencing embryonic development. © 2015 Wiley Periodicals, Inc.

Lacrimal drainage-associated lymphoid tissue (LDALT): a part of the human mucosal immune system.

PubMed

Knop, E; Knop, N

2001-03-01

Mucosa-associated lymphoid tissue (MALT) specifically protects mucosal surfaces. In a previous study of the human conjunctiva, evidence was also found for the presence of MALT in the lacrimal sac. The present study, therefore, aims to investigate its morphology and topographical distribution in the human lacrimal drainage system. Lacrimal drainage systems (n = 51) obtained from human cadavers were investigated by clearing flat wholemounts or by serial sections of tissue embedded in paraffin, OCT compound, or epoxy resin. These were further analyzed by histology, immunohistochemistry, and electron microscopy. All specimens showed the presence of lymphocytes and plasma cells as a diffuse lymphoid tissue in the lamina propria, together with intraepithelial lymphocytes and occasional high endothelial venules (HEV). It formed a narrow layer along the canaliculi that became thicker in the cavernous parts. The majority of lymphocytes were T cells, whereas B cells were interspersed individually or formed follicular centers. T cells were positive for CD8 and the human mucosa lymphocyte antigen (HML-1). Most plasma cells were positive for IgA and the overlying epithelium expressed its transporter molecule secretory component (SC). Basal mucous glands were present in the lacrimal canaliculi and in the other parts accompanied by alveolar and acinar glands, all producing IgA-rich secretions. Primary and secondary lymphoid follicles possessing HEV were present in about half of the specimens. The term lacrimal drainage-associated lymphoid tissue (LDALT) is proposed here to describe the lymphoid tissue that is regularly present and belongs to the common mucosal immune system and to the secretory immune system. It is suggested that it may form a functional unit together with the lacrimal gland and conjunctiva, connected by tear flow, lymphocyte recirculation, and probably the neural reflex arc, and play a major role in preserving ocular surface integrity.

Comparison of several oximes on reactivation of soman-inhibited blood, brain and tissue cholinesterase activity in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shih, T.M.

1993-12-31

The ability of three oximes, HI-6, MMB-4 and ICD-467, to reactivate cholinesterase (ChE) inhibited by the organophosphorus compound soman was compared in blood (plasma and erythrocytes), brain regions (including spinal cord) and peripheral tissues of rats. Animals were intoxicated with soman (100 ttg/kg. SC; equivalent to 0.9 x LDs0 dose) and treated 1 min later with one of these oximes (100 or 200 ttmo1/kg, IM). Toxic sign scores and total tissue ChE activities were determined 30 min later. Soman markedly inhibited ChE activity in blood (93 - 96%), brain regions (ranging from 78% to 95%), and all peripheral tissues (rangingmore » from 48.9% to 99.8%) except liver (11.9%). In blood, treatment with HI-6 or ICD-467 resulted in significant reactivation of soman-inhibited ChE. in contrast, MMB-4 was completely ineffective. HI-6 and ICD-467 were equally effective at the high dose. At the low dose ICD-467 treatment resulted in significantly higher plasma ChE than Hl-6 treatment, whereas HI-6 treatment resulted in higher erythrocyte ChE than ICD-467 treatment. However, none of these three oximesreactivated or protected soman-inhibited ChE in the brain. In all peripheral tissues (except liver) studied, MMB-4 was not effective. 111-6 reactivated soman-inhibited ChE in all tis- sues except lung, heart, and skeletal muscle. ICD-467 was highly effective in reactivating ChE in all tissues and afforded a complete recovery of ChE to control levels in Intercostal muscle and salivary gland. Oxime treatments did not modify the toxic scores produced by soman.« less

Menthone aryl acid hydrazones: a new class of anticonvulsants.

PubMed

Jain, Jainendra; Kumar, Y; Sinha, Reema; Kumar, Rajeev; Stables, James

2011-01-01

A series of ten compounds (Compounds J(1)-J(10)) of (±) 3-menthone aryl acid hydrazone was synthesized and characterized by thin layer chromatography and spectral analysis. Synthesized compounds were evaluated for anticonvulsant activity after intraperitoneal (i.p) administration to mice by maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure method and minimal clonic seizure test. Minimal motor impairment was also determined for these compounds. Results obtained showed that four compounds out of ten afforded significant protection in the minimal clonic seizure screen at 6 Hz. Compound J(6), 4-Chloro-N-(2-isopropyl-5-methylcyclohexylidene) benzohydrazide was found to be the most active compound with MES ED(50) of 16.1 mg/kg and protective index (pI) of greater than 20, indicating that (±) 3-menthone aryl acid hydrazone possesses better and safer anticonvulsant properties than other reported menthone derivatives viz. menthone Schiff bases, menthone semicarbazides and thiosemicarbazides.

Cable Feedthrough Between Liquid Oxygen And Ambient

NASA Technical Reports Server (NTRS)

Myers, Don A.

1992-01-01

Encapsulant and back pressure provide double protection. Cable-feedthrough tube between ambient air and interior of vessel containing liquid oxygen protects external instrumentation and cable from oxygen. Cable in tube surrounded by potting compound. Provides flow of gaseous nitrogen to dilute oxidant and makes it harmless in case of leakage through crack in potting compound.

21 CFR 500.86 - Marker residue and target tissue.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Regulation of Carcinogenic Compounds Used in Food-Producing Animals § 500.86 Marker residue and target tissue. (a) For each edible tissue, the sponsor shall... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Marker residue and target tissue. 500.86 Section...

21 CFR 500.86 - Marker residue and target tissue.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Regulation of Carcinogenic Compounds Used in Food-Producing Animals § 500.86 Marker residue and target tissue. (a) For each edible tissue, the sponsor shall... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Marker residue and target tissue. 500.86 Section...

21 CFR 500.86 - Marker residue and target tissue.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Regulation of Carcinogenic Compounds Used in Food-Producing Animals § 500.86 Marker residue and target tissue. (a) For each edible tissue, the sponsor shall... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Marker residue and target tissue. 500.86 Section...

Equilibrium Passive Sampling of POP in Lipid-Rich and Lean Fish Tissue: Quality Control Using Performance Reference Compounds.

PubMed

Rusina, Tatsiana P; Carlsson, Pernilla; Vrana, Branislav; Smedes, Foppe

2017-10-03

Passive sampling is widely used to measure levels of contaminants in various environmental matrices, including fish tissue. Equilibrium passive sampling (EPS) of persistent organic pollutants (POP) in fish tissue has been hitherto limited to application in lipid-rich tissue. We tested several exposure methods to extend EPS applicability to lean tissue. Thin-film polydimethylsiloxane (PDMS) passive samplers were exposed statically to intact fillet and fish homogenate and dynamically by rolling with cut fillet cubes. The release of performance reference compounds (PRC) dosed to passive samplers prior to exposure was used to monitor the exchange process. The sampler-tissue exchange was isotropic, and PRC were shown to be good indicators of sampler-tissue equilibration status. The dynamic exposures demonstrated equilibrium attainment in less than 2 days for all three tested fish species, including lean fish containing 1% lipid. Lipid-based concentrations derived from EPS were in good agreement with lipid-normalized concentrations obtained using conventional solvent extraction. The developed in-tissue EPS method is robust and has potential for application in chemical monitoring of biota and bioaccumulation studies.

Plants and their bioactive compounds with the potential to enhance mechanisms of inherited cardiac regeneration.

PubMed

Zhou, Zhen; Li, Dianbin; Zhou, Hua; Lin, Xiaoli; Li, Censing; Tang, Mingfeng; Feng, Zhou; Li, Ming

2015-06-01

This article reviews the current progress and research indications in the application of natural plant compounds with the potential for the treatment of cardiovascular diseases. Our understanding of how to apply natural plant compounds to enhance mechanisms of inherited cardiac regeneration, which is physiologically pertinent to myocyte turnover or minor cardiac repair, for substantial cardiac regeneration to repair pathological heart injuries is discussed. Although significant progress has been made in the application of natural plant compounds for therapy of heart diseases, the understanding or the application of these compounds specifically for enhancing mechanisms of inherited cardiac regeneration for the treatment of cardiovascular diseases is little. Recent recognition of some natural plant compounds that can repair damaged myocardial tissues through enhancing mechanisms of inherited cardiac regeneration has offered an alternative for clinical translation. Application of natural plant compounds, which show the activity of manipulating gene expressions in such a way to enhance mechanisms of inherited cardiac regeneration for cardiac repair, may provide a promising strategy for the reconstruction of damaged cardiac tissues due to cardiovascular diseases. Georg Thieme Verlag KG Stuttgart · New York.

Compounds with species and cell type specific toxicity identified in a 2000 compound drug screen of neural stem cells and rat mixed cortical neurons.

PubMed

Malik, Nasir; Efthymiou, Anastasia G; Mather, Karly; Chester, Nathaniel; Wang, Xiantao; Nath, Avindra; Rao, Mahendra S; Steiner, Joseph P

2014-12-01

Human primary neural tissue is a vital component for the quick and simple determination of chemical compound neurotoxicity in vitro. In particular, such tissue would be ideal for high-throughput screens that can be used to identify novel neurotoxic or neurotherapeutic compounds. We have previously established a high-throughput screening platform using human induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) and neurons. In this study, we conducted a 2000 compound screen with human NSCs and rat cortical cells to identify compounds that are selectively toxic to each group. Approximately 100 of the tested compounds showed specific toxicity to human NSCs. A secondary screen of a small subset of compounds from the primary screen on human iPSCs, NSC-derived neurons, and fetal astrocytes validated the results from >80% of these compounds with some showing cell specific toxicity. Amongst those compounds were several cardiac glycosides, all of which were selectively toxic to the human cells. As the screen was able to reliably identify neurotoxicants, many with species and cell-type specificity, this study demonstrates the feasibility of this NSC-driven platform for higher-throughput neurotoxicity screens. Published by Elsevier B.V.

A generic biokinetic model for carbon-14 labelled compounds

NASA Astrophysics Data System (ADS)

Manger, Ryan Paul

Carbon-14, a radioactive nuclide, is used in many industrial applications. Due to its wide range of uses in industry, many workers are at risk of accidental internal exposure to 14C. Being a low energy beta emitter, 14C is not a significant external radiation hazard, but the internal consequences posed by 14C are important, especially because of its long half life of 5730 years [46]. The current biokinetic model recommended by the International Commission on Radiological Protection (ICRP) is a conservative estimate of how radiocarbon is treated by the human body. The ICRP generic radiocarbon model consists of a single compartment representing the entire human body. This compartment has a biological half life of 40 days yielding an effective dose coefficient of 5.8x10-10 Sv B q-1 [44, 45, 49, 53, 54]. This overestimates the dose of all radiocarbon compounds that have been studied [96]. An improved model has been developed that includes and alimentary tract, a urinary bladder, CO2 model, and an "Other" compartment used to model systemic tissues. The model can be adapted to replicate any excretion curve and excretion pattern. In addition, the effective dose coefficient produced by the updated model is near the mean effective dose coefficient of carbon compounds that have been considered in this research. The major areas of improvement are: more anatomically significant, a less conservative dose coefficient, and the ability to manipulate the model for known excretion data. Due to the wide variety of carbon compounds, it is suggested that specific biokinetic models be implemented for known radiocarbon substances. If the source of radiocarbon is dietary, then the physiologically based model proposed by Whillans [102] that splits all ingested radiocarbon compounds into carbohydrates, fats, and proteins should be used.

Short-term Effects of Date Palm Extract (Phoenix dactylifera) on Ischemia/Reperfusion Injury Induced by Testicular Torsion/Detorsion in Rats.

PubMed

Jahromi, Alireza Raayat; Rasooli, Rokhsana; Kamali, Younes; Ahmadi, Nasrollah; Sattari, Ehsan

2017-01-01

Antioxidants are potent scavengers of free radicals and have beneficial effects on human health. The aim of this study was to investigate the potential protective antioxidant activity of the edible portion of date fruit extract in an experimental testicular torsion/detorsion (T/D) model in rats. To investigate the potential protective effects of date palm (DP), 30 male Spraque-Dawley rats were divided into three groups: sham-operated, T/D, and T/D + DP-treated (500 mg/kg, PO) groups. Testicular ischemia was induced via keeping the left testis under 720° clockwise torsion for 2 h (h), afterward, detorsion was performed. All rats were sacrificed 4 h after detorsion. Serum malondialdehyde (MDA) concentration, total oxidative status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and histopathological damage score were evaluated. Serum MDA, TOS, and OSI levels rose significantly in the T/D group. These values were lower in the T/D + DP group. TAS values decreased significantly in T/D group and rose in T/D + DP group. Severe injury was seen in the twisted testes of T/D group. In contrast, ipsilateral-twisted testicular tissue in the DP-treated group showed moderate-to-mild changes. Contralateral testicular tissue in the T/D group had a mild-to-moderate tissue injury; meanwhile, treated group revealed normal-to-mild changes. Spermatogenesis was significantly improved in DP-treated group when compared with the T/D group. The findings suggest a possible protective effect of DP against testicular oxidative damage induced by T/D; however, more detailed studies are warranted. Given the presence of several phenolic compounds possessing high antioxidant activity in DP, it could potentially be used to reduce testis ischemia/reperfusion-induced damage. Abbreviations Used : TAS: Total antioxidant status,TOS: Total oxidative status; OSI: Oxidative stress index; MDA: Malondialdehyde; C: Congestion; H: Hemorrhage, E: Edema; SG: Sloughed germinal cells; SA: Spermatogenesis arrest; STD: Seminiferous tubules disorganization; STA: Seminiferous tubules atrophy; G: Giant cells; T/D: Torsion/detorsion; DP: Date palm.

Optical probe with light fluctuation protection

DOEpatents

Da Silva, Luiz B.; Chase, Charles L.

2003-11-11

An optical probe for tissue identification includes an elongated body. Optical fibers are located within the elongated body for transmitting light to and from the tissue. Light fluctuation protection is associated with the optical fibers. In one embodiment the light fluctuation protection includes a reflective coating on the optical fibers to reduce stray light. In another embodiment the light fluctuation protection includes a filler with very high absorption located within the elongated body between the optical fibers.

Reversal of Trimethyltin-Induced Learning and Memory Deficits by 3,5-Dicaffeoylquinic Acid.

PubMed

Kang, Jin Yong; Park, Seon Kyeong; Guo, Tian Jiao; Ha, Jeong Su; Lee, Du Sang; Kim, Jong Min; Lee, Uk; Kim, Dae Ok; Heo, Ho Jin

2016-01-01

The antiamnesic effect of 3,5-dicaffeoylquinic acid (3,5-diCQA) as the main phenolic compound in Artemisia argyi H. extract on cognitive dysfunction induced by trimethyltin (TMT) (7.1  μ g/kg of body weight; intraperitoneal injection) was investigated in order to assess its ameliorating function in mice. In several behavioral tests, namely, the Y-maze, passive avoidance, and Morris water maze (MWM) test, 3,5-diCQA significantly ameliorated learning and memory deficits. After the behavioral tests, brain tissues from the mice were analyzed to characterize the basis of the neuroprotective effect. Acetylcholine (ACh) levels increased, whereas the activity of acetylcholinesterase (AChE) decreased upon administration of 3,5-diCQA. In addition, 3,5-diCQA effectively protected against an increase in malondialdehyde (MDA) content, an increase in the oxidized glutathione (GSH) ratio, and a decline of total superoxide dismutase (SOD) level. 3,5-diCQA may prevent neuronal apoptosis through the protection of mitochondrial activities and the repression of apoptotic signaling molecules such as p-Akt, BAX, and p-tau (Ser 404).

Reversal of Trimethyltin-Induced Learning and Memory Deficits by 3,5-Dicaffeoylquinic Acid

PubMed Central

Kang, Jin Yong; Park, Seon Kyeong; Guo, Tian Jiao; Ha, Jeong Su; Lee, Du Sang; Kim, Jong Min; Lee, Uk; Kim, Dae Ok

2016-01-01

The antiamnesic effect of 3,5-dicaffeoylquinic acid (3,5-diCQA) as the main phenolic compound in Artemisia argyi H. extract on cognitive dysfunction induced by trimethyltin (TMT) (7.1 μg/kg of body weight; intraperitoneal injection) was investigated in order to assess its ameliorating function in mice. In several behavioral tests, namely, the Y-maze, passive avoidance, and Morris water maze (MWM) test, 3,5-diCQA significantly ameliorated learning and memory deficits. After the behavioral tests, brain tissues from the mice were analyzed to characterize the basis of the neuroprotective effect. Acetylcholine (ACh) levels increased, whereas the activity of acetylcholinesterase (AChE) decreased upon administration of 3,5-diCQA. In addition, 3,5-diCQA effectively protected against an increase in malondialdehyde (MDA) content, an increase in the oxidized glutathione (GSH) ratio, and a decline of total superoxide dismutase (SOD) level. 3,5-diCQA may prevent neuronal apoptosis through the protection of mitochondrial activities and the repression of apoptotic signaling molecules such as p-Akt, BAX, and p-tau (Ser 404). PMID:28105250

Tissue distribution comparison between healthy and fatty liver rats after oral administration of hawthorn leaf extract.

PubMed

Yin, Jingjing; Qu, Jianguo; Zhang, Wenjie; Lu, Dongrui; Gao, Yucong; Ying, Xixiang; Kang, Tingguo

2014-05-01

Hawthorn leaves, a well-known traditional Chinese medicine, have been widely used for treating cardiovascular and fatty liver diseases. The present study aimed to investigate the therapeutic basis treating fatty liver disease by comparing the tissue distribution of six compounds of hawthorn leaf extract (HLE) in fatty liver rats and healthy rats after oral administration at first day, half month and one month, separately. Therefore, a sensitive and specific HPLC method with internal standard was developed and validated to determine chlorogenic acid, vitexin-4''-O-glucoside, vitexin-2''-O-rhamnoside, vitexin, rutin and hyperoside in the tissues including heart, liver, spleen, kidney, stomach and intestine. The results indicated that the six compounds in HLE presented some bioactivity in treating rat fatty liver as the concentrations of the six compounds varied significantly in inter- and intragroup comparisons (healthy and/or fatty liver group). Copyright © 2013 John Wiley & Sons, Ltd.

Estrogenic alkylphenols in fish tissues, sediments, and waters from the U.K. Tyne and Tees estuaries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lye, C.M.; Frid, C.L.J.; Gill, M.E.

1999-04-01

Nonylphenols and related compounds are common products of biodegradation of a large group of nonionic surfactants, the nonylphenol polyethoxylates. Many of these compounds are known to be environmentally persistent and to elicit estrogenic response in both mammals and fish. In this study, nonylphenol (NP), nonylphenol monoethoxylate (NP1EO), and octylphenol (OP) were found in tissues of mature male flounder, Platichthys flesus, and in tissues of juvenile flounder. These fish also showed detectable levels of the yolk protein vitellogenin in their plasma, indicative of estrogenic exposure. The compounds were also found in discharges from a major sewage treatment works and in sedimentsmore » from two estuaries in north-east England; the highest levels from the highly industrialized Tees and lower levels from the industrialized/urbanized Tyne estuary. The implications of these findings for fish populations are discussed.« less

Organohalogen concentrations in blood and adipose tissue of Southern Beaufort Sea polar bears.

PubMed

Bentzen, T W; Muir, D C G; Amstrup, S C; O'Hara, T M

2008-11-15

We analyzed 151 organohalogen chemicals (OHCs) in whole blood and subcutaneous fat of 57 polar bears sampled along the Alaskan Beaufort Sea coast in spring, 2003. All major organochlorine pesticides, PCBs, PBDEs and their congeners were assessed. Concentrations of most OHCs continue to be lower among Southern Beaufort Sea polar bears than reported for other populations. Additionally, toxaphenes and related compounds were assessed in adipose tissue, and 8 perflourinated compounds (PFCs) were examined in blood. Perfluorooctane sulfonate (PFOS) concentrations exceeded those of any other contaminant measured in blood. SigmaChlordane concentrations were higher in females, and both SigmaPCBs and SigmaChlordane concentrations in adipose tissue decreased significantly with age. The rank order of OHC mean concentrations; SigmaPCB>Sigma10PCB>PCB153>SigmaChlordane>Oxychlordane>PCB180>SigmaHCH>beta-HCH>SigmaDDT>p,p-DDE>SigmaPBDE>HCB>Toxaphene was similar for compounds above detection limits in both fat and blood. Although correlation between OHC concentrations in blood and adipose tissue was examined, the predictability of concentrations in one matrix for the other was limited.

Organohalogen concentrations in blood and adipose tissue of Southern Beaufort Sea polar bears

USGS Publications Warehouse

Bentzen, T.W.; Muir, D.C.G.; Amstrup, Steven C.; O'Hara, T. M.

2008-01-01

We analyzed 151 organohalogen chemicals (OHCs) in whole blood and subcutaneous fat of 57 polar bears sampled along the Alaskan Beaufort Sea coast in spring, 2003. All major organochlorine pesticides, PCBs, PBDEs and their congeners were assessed. Concentrations of most OHCs continue to be lower among Southern Beaufort Sea polar bears than reported for other populations. Additionally, toxaphenes and related compounds were assessed in adipose tissue, and 8 perflourinated compounds (PFCs) were examined in blood. Perfluorooctane sulfonate (PFOS) concentrations exceeded those of any other contaminant measured in blood. ??Chlordane concentrations were higher in females, and both ??PCBs and ??Chlordane concentrations in adipose tissue decreased significantly with age. The rank order of OHC mean concentrations; ??PCB > ??10PCB > PCB153 > ??Chlordane > Oxychlordane > PCB180 > ??HCH > ??-HCH > ??DDT > p,p-DDE > ??PBDE > HCB > Toxaphene was similar for compounds above detection limits in both fat and blood. Although correlation between OHC concentrations in blood and adipose tissue was examined, the predictability of concentrations in one matrix for the other was limited. ?? 2008 Elsevier B.V.

Sulfur compounds in therapy: Radiation-protective agents, amphetamines, and mucopolysaccharide sulfation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foye, W.O.

1992-09-01

Sulfur-containing compounds have been used in the search for whole-body radiation-protective compounds, in the design of amphetamine derivatives that retain appetite-suppressive effects but lack most behavioral effects characteristic of amphetamines, and in the search for the cause of kidney stone formation in recurrently stoneforming patients. Organic synthetic procedures were used to prepare radiation-protective compounds having a variety of sulfur-containing functional groups, and to prepare amphetamine derivatives having electron-attracting sulfur functions. In the case of the kidney stone causation research, isolation of urinary mucopolysaccharides (MPS) from recurrently stoneforming patients was carried out and the extent of sulfation of the MPS wasmore » determined by electrophoresis. Whole-body radiation-protective agents with a high degree of protection against lethal doses of gamma-radiation in mice were found in a series of quinolinium and pyridinium bis(methylthio) and methylthio amino derivatives. Mechanism studies showed that the copper complexes of these agents mimicked the beneficial action of superoxide dismutase. Electron-attracting sulfur-containing functions on amphetamine nitrogen, as well as 4'-amino nitrogen provided amphetamine derivatives with good appetite-suppressant effects and few or no adverse behavioral effects. Higher than normal levels of sulfation of the urinary MPS of stone formers suggested a cause for recurrent kidney stone formation. A sulfation inhibitor was found to prevent recurrence of stone formation and inhibit growth of existing stones. The inclusion of various sulfur-containing functions in organic molecules yielded compounds having whole-body radiation protection from lethal doses of gamma-radiation in animals. The presence of electron-attracting sulfur functions in amphetamine gave derivatives that retained appetite-suppressant effects and eliminated most adverse behavioral effects.« less

Attenuation of CCl4-Induced Oxidative Stress and Hepatonephrotoxicity by Saudi Sidr Honey in Rats.

PubMed

Al-Yahya, Mohammed; Mothana, Ramzi; Al-Said, Mansour; Al-Dosari, Mohammed; Al-Musayeib, Nawal; Al-Sohaibani, Mohammed; Parvez, Mohammad Khalid; Rafatullah, Syed

2013-01-01

The present study was undertaken to investigate the possible protective effect of Saudi Sidr honey (SSH) on carbon tetrachloride (CCl4) induced oxidative stress and liver and kidney damage in rat. Moreover, the antioxidant activity and the phenolic and flavonoidal contents were determined. The hepatorenal protective activity of the SSH was determined by assessing biochemical, hematological, and histological parameters. Serum transaminases, ALP, GGT, creatinine, bilirubin urea, uric acid, and MDA level in liver and kidney tissues were significantly elevated, and the antioxidant status of nonprotein sulfhydryls, albumin, and total protein levels in liver and kidney were declined significantly in CCl4 alone treated animals. Pretreatment with SSH and silymarin prior to the administration of CCl4 significantly prevented the increase of the serum levels of enzyme markers and reduced oxidative stress. SSH also exhibited a significant lipid-lowering effect and caused an HDL-C enhanced level in serum. The histopathological evaluation of the liver and kidney also revealed that honey protected incidence of both liver and kidney lesions. Moreover, SSH showed a strong antioxidant activity in DPPH and β -carotene-linoleic acid assays. SSH was found to contain phenolic compounds. Additionally, the SSH supplementation restored the hepatocytes viability against 2',7'-dichlorofluorescein (DCF) toxicity in ex vivo test.

Attenuation of CCl4-Induced Oxidative Stress and Hepatonephrotoxicity by Saudi Sidr Honey in Rats

PubMed Central

Al-Yahya, Mohammed; Mothana, Ramzi; Al-Said, Mansour; Al-Dosari, Mohammed; Al-Musayeib, Nawal; Al-Sohaibani, Mohammed; Parvez, Mohammad Khalid; Rafatullah, Syed

2013-01-01

The present study was undertaken to investigate the possible protective effect of Saudi Sidr honey (SSH) on carbon tetrachloride (CCl4) induced oxidative stress and liver and kidney damage in rat. Moreover, the antioxidant activity and the phenolic and flavonoidal contents were determined. The hepatorenal protective activity of the SSH was determined by assessing biochemical, hematological, and histological parameters. Serum transaminases, ALP, GGT, creatinine, bilirubin urea, uric acid, and MDA level in liver and kidney tissues were significantly elevated, and the antioxidant status of nonprotein sulfhydryls, albumin, and total protein levels in liver and kidney were declined significantly in CCl4 alone treated animals. Pretreatment with SSH and silymarin prior to the administration of CCl4 significantly prevented the increase of the serum levels of enzyme markers and reduced oxidative stress. SSH also exhibited a significant lipid-lowering effect and caused an HDL-C enhanced level in serum. The histopathological evaluation of the liver and kidney also revealed that honey protected incidence of both liver and kidney lesions. Moreover, SSH showed a strong antioxidant activity in DPPH and β-carotene-linoleic acid assays. SSH was found to contain phenolic compounds. Additionally, the SSH supplementation restored the hepatocytes viability against 2′,7′-dichlorofluorescein (DCF) toxicity in ex vivo test. PMID:23533498

Heme oxygenase/carbon monoxide signaling pathways: regulation and functional significance.

PubMed

Ryter, Stefan W; Otterbein, Leo E; Morse, Danielle; Choi, Augustine M K

2002-01-01

Carbon monoxide (CO), a gaseous second messenger, arises in biological systems during the oxidative catabolism of heme by the heme oxygenase (HO) enzymes. HO exists as constitutive (HO-2, HO-3) and inducible isoforms (HO-1), the latter which responds to regulation by multiple stress-stimuli. HO-1 confers protection in vitro and in vivo against oxidative cellular stress. Although the redox active compounds that are generated from HO activity (i.e. iron, biliverdin-IXalpha, and bilirubin-IXa) potentially modulate oxidative stress resistance, increasing evidence points to cytoprotective roles for CO. Though not reactive, CO regulates vascular processes such as vessel tone, smooth muscle proliferation, and platelet aggregation, and possibly functions as a neurotransmitter. The latter effects of CO depend on the activation of guanylate cyclase activity by direct binding to the heme moiety of the enzyme, stimulating the production of cyclic 3':5'-guanosine monophosphate. CO potentially interacts with other intracellular hemoprotein targets, though little is known about the functional significance of such interactions. Recent progress indicates that CO exerts novel anti-inflammatory and anti-apoptotic effects dependent on the modulation of the p38 mitogen activated protein kinase (MAPK)-signaling pathway. By virtue of these effects, CO confers protection in oxidative lung injury models, and likely plays a role in HO-1 mediated tissue protection.

Gastroprotective Effects of Lion's Mane Mushroom Hericium erinaceus (Bull.:Fr.) Pers. (Aphyllophoromycetideae) Extract against Ethanol-Induced Ulcer in Rats

PubMed Central

Wong, Jing-Yang; Raman, Jegadeesh; Kuppusamy, Umah Rani; Sabaratnam, Vikineswary

2013-01-01

Hericium erinaceus is a famous tonic in oriental medicine. The gastroprotective effects of aqueous extract of H. erinaceus against ethanol-induced ulcers in Sprague Dawley rats were investigated. The possible involvements of lipid peroxidation, superoxide dismutase, and catalase were also investigated. Acute toxicity study was performed. The effects of aqueous extract of H. erinaceus on the ulcer areas, ulcer inhibition, gastric wall mucus, gross and histological gastric lesions, antioxidant levels, and malondialdehyde (MDA) contents were evaluated in ethanol-induced ulcer in vivo. In acute toxicity study, a high dose of 5 g/kg did not manifest any toxicological signs in rats. The extract promoted ulcer protection as ascertained by a significant reduction of the ulcer area. Furthermore, it exhibited a significant protection activity against gastric mucosal injury by preventing the depletion of antioxidant enzymes. The level of MDA was also limited in rat stomach tissues when compared with the ulcer control group. Immunohistochemistry showed upregulation of HSP70 protein and downregulation of BAX protein in rats pretreated with the extract. The aqueous extract of H. erinaceus protected gastric mucosa in our in vivo model. It is speculated that the bioactive compounds present in the extract may play a major role in gastroprotective activity. PMID:24302966

Process for the preparation of protected 3-amino-1,2-dihydroxypropane acetal and derivatives thereof

DOEpatents

Hollingsworth, Rawle I.; Wang, Guijun

2000-01-01

A process for producing protected 3-amino-1,2-dihydroxypropane acetal, particularly in chiral forms, for use as an intermediate in the preparation of various 3-carbon compounds which are chiral. In particular, the present invention relates to the process for preparation of 3-amino-1,2-dihydroxypropane isopropylidene acetal. The protected 3-amino-1,2-dihydroxypropane acetal is a key intermediate to the preparation of chiral 3-carbon compounds which in turn are intermediates to various pharmaceuticals.

OBO-Protected Pyruvates as Reagents for the Synthesis of Functionalized Heteroaromatic Compounds.

PubMed

Alves Esteves, C Henrique; Koyioni, Maria; Christensen, Kirsten E; Smith, Peter D; Donohoe, Timothy J

2018-06-15

Pd-catalyzed α-arylation of methyl-OBO-ketone (OBO = 4-methyl-2,6,7-trioxabicyclo[2.2.2]octan-1-yl) gives rise to arylated OBO-protected pyruvates. By appropriate prefunctionalization of the aryl ring or by subsequent functionalization at the α-carbonyl position of the arylated OBO-ketones, useful diketo OBO-protected carboxylates can be generated. Cyclization, aromatization, and OBO deprotection of these intermediates, using two distinct routes, gives access to valuable α-acyl heteroaromatic compounds.

Noise Protection

NASA Technical Reports Server (NTRS)

1980-01-01

Environmental Health Systems puts forth an increasing effort in the U.S. to develop ways of controlling noise, particularly in industrial environments due to Federal and State laws, labor union insistence and new findings relative to noise pollution impact on human health. NASA's Apollo guidance control system aided in the development of a noise protection product, SMART. The basis of all SMART products is SMART compound a liquid plastic mixture with exceptional energy/sound absorbing qualities. The basic compound was later refined for noise protection use.

Influence of methionine and vitamin E on fluoride concentration in bones and teeth of rats exposed to sodium fluoride in drinking water.

PubMed

Błaszczyk, Iwona; Birkner, Ewa; Gutowska, Izabela; Romuk, Ewa; Chlubek, Dariusz

2012-06-01

Increased exposure to fluorine-containing compounds leads to accumulation of fluorides in hard tissues of bones and teeth, which may result in numerous skeletal and dental disorders. This study evaluates the influence of methionine and vitamin E on fluoride concentration in bones and teeth of rats subjected to long-term exposure to sodium fluoride in drinking water. The study was conducted in 30 3-month-old female Wistar FL rats. The animals were divided into five groups, six rats per group. The control group consisted of rats receiving only distilled water as drinking water. All other groups received NaF in the amount of 10 mg/kg of body mass/day in their drinking water. In addition, respective animal groups received: NaF + Met group--10 mg of methionine/kg of body mass/day, NaF + Met + E group--10 mg of methionine/kg of body mass/day and 3 mg of vitamin E (tocopheroli acetas)/rat/day and NaF + E group--3 mg of vitamin E/rat/day. Femoral bones and incisor teeth were collected for the study, and the fluoride concentration was determined using a fluoride ion-selective electrode. Fluoride concentration in both bones and teeth was found to be higher in the NaF and NaF + Met groups compared to the control group. In groups NaF + Met + E and NaF + E, the study material contained much lower fluoride concentration compared to the NaF group, while the effect was more prominent in the NaF + E group. The results of the studies indicate that methionine and vitamin E have opposite effects on accumulation of fluorides in hard tissue in rats. By stimulating fluoride accumulation, methionine reduces the adverse effect of fluorides on soft tissue, while vitamin E, which prevents excessive accumulation of fluorides in bones and teeth, protects these tissues from fluorosis. Therefore, it seems that combined application of both compounds would be optimal for the prevention of the adverse effects of chronic fluoride intoxication.

Yellow-Cedar, Callitropsis (Chamaecyparis) nootkatensis, Secondary Metabolites, Biological Activities, and Chemical Ecology.

PubMed

Karchesy, Joseph J; Kelsey, Rick G; González-Hernández, M P

2018-05-01

Yellow-cedar, Callitropsis nootkatensis, is prevalent in coastal forests of southeast Alaska, western Canada, and inland forests along the Cascades to northern California, USA. These trees have few microbial or animal pests, attributable in part to the distinct groups of biologically active secondary metabolites their tissues store for chemical defense. Here we summarize the new yellow-cedar compounds identified and their biological activities, plus new or expanded activities for tissues, extracts, essential oils and previously known compounds since the last review more than 40 years ago. Monoterpene hydrocarbons are the most abundant compounds in foliage, while heartwood contains substantial quantities of oxygenated monoterpenes and oxygenated sesquiterpenes, with one or more tropolones. Diterpenes occur in foliage and bark, whereas condensed tannins have been isolated from inner bark. Biological activities expressed by one or more compounds in these groups include fungicide, bactericide, sporicide, acaricide, insecticide, general cytotoxicity, antioxidant and human anticancer. The diversity of organisms impacted by whole tissues, essential oils, extracts, or individual compounds now encompasses ticks, fleas, termites, ants, mosquitoes, bacteria, a water mold, fungi and browsing animals. Nootkatone, is a heartwood component with sufficient activity against arthropods to warrant research focused toward potential development as a commercial repellent and biopesticide for ticks, mosquitoes and possibly other arthropods that vector human and animal pathogens.

Recent Applications of Coaxial and Emulsion Electrospinning Methods in the Field of Tissue Engineering

PubMed Central

McClellan, Phillip; Landis, William J.

2016-01-01

Abstract Electrospinning has emerged as an effective method of producing nanoscale fibers for use in multiple fields of study. One area of significant interest is nanofiber utilization for tissue engineering because the nanofibrous mats can mimic the native extracellular matrix of biological tissues. A logical next step is the inclusion of certain molecules and compounds to accelerate or increase the efficacy of tissue regeneration. Two methods are under scrutiny for their capability to encapsulate therapeutic compounds within electrospun nanofibers: emulsion and coaxial electrospinning. Both have advantages and disadvantages, which need to be taken into careful consideration when deciding to use them in a specific application. Several examples are provided here to highlight the vast potential of multilayered nanofibers as well as the emergence of new techniques to produce three-dimensional scaffolds of nanofibers for use in the field of tissue engineering. PMID:27610268

Compound parabolic concentrator probe for efficient light collection in spectroscopy of biological tissue

NASA Astrophysics Data System (ADS)

Tanaka, Kazunori; Pacheco, Marcos T. T.; Brennan, James F., III; Itzkan, Irving; Berger, Andrew J.; Dasari, Ramachandra R.; Feld, Michael S.

1996-02-01

We describe a compound parabolic concentrator (CPC)-based probe for enhanced signal collection in the spectroscopy of biological tissues. Theoretical considerations governing signal enhancement compared with conventional collection methods are given. A ray-tracing program was used to analyze the throughput of CPC's with shape deviations and surface imperfections. A modified CPC shape with 99% throughput was discovered. A 4.4-mm-long CPC was manufactured and incorporated into an optical fiber-based near-infrared Raman spectrometer system. For human tissue samples, light collection was enhanced by a factor of 7 compared with collection with 0.29-NA optical fibers.

Methods of analysis by the U.S. Geological Survey National Water Quality Laboratory; determination of chlorinated pesticides in aquatic tissue by capillary-column gas chromatography with electron-capture detection

USGS Publications Warehouse

Leiker, Thomas J.; Madsen, J.E.; Deacon, J.R.; Foreman, W.T.

1995-01-01

A method for the determination of chlorinated organic compounds in aquatic tissue by dual capillary-column gas chromatography with electron-capture detection is described. Whole-body-fish or corbicula tissue is homogenized, Soxhlet extracted, lipid removed by gel permeation chromatography, and fractionated using alumina/silica adsorption chromatography. The extracts are analyzed by dissimilar capillary-column gas chromatography with electron-capture detection. The method reporting limits are 5 micrograms per kilogram (μg/kg) for chlorinated compounds, 50 μg/kg for polychlorinated biphenyls, and 200 μg/kg for toxaphene.

40 CFR 721.3100 - Oligomeric silicic acid ester compound with a hy-droxyl-al-kyla-mine.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Oligomeric silicic acid ester compound with a hy-droxyl-al-kyla-mine. 721.3100 Section 721.3100 Protection of Environment ENVIRONMENTAL... hy-droxyl-al-kyla-mine. (a) Chemical substance and significant new uses subject to reporting. (1) The...

40 CFR 721.3100 - Oligomeric silicic acid ester compound with a hy-droxyl-al-kyla-mine.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Oligomeric silicic acid ester compound with a hy-droxyl-al-kyla-mine. 721.3100 Section 721.3100 Protection of Environment ENVIRONMENTAL... hy-droxyl-al-kyla-mine. (a) Chemical substance and significant new uses subject to reporting. (1) The...

40 CFR 721.3100 - Oligomeric silicic acid ester compound with a hy-droxyl-al-kyla-mine.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Oligomeric silicic acid ester compound with a hy-droxyl-al-kyla-mine. 721.3100 Section 721.3100 Protection of Environment ENVIRONMENTAL... hy-droxyl-al-kyla-mine. (a) Chemical substance and significant new uses subject to reporting. (1) The...

40 CFR 721.3100 - Oligomeric silicic acid ester compound with a hy-droxyl-al-kyla-mine.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Oligomeric silicic acid ester compound with a hy-droxyl-al-kyla-mine. 721.3100 Section 721.3100 Protection of Environment ENVIRONMENTAL... hy-droxyl-al-kyla-mine. (a) Chemical substance and significant new uses subject to reporting. (1) The...

40 CFR 721.3100 - Oligomeric silicic acid ester compound with a hy-droxyl-al-kyla-mine.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Oligomeric silicic acid ester compound with a hy-droxyl-al-kyla-mine. 721.3100 Section 721.3100 Protection of Environment ENVIRONMENTAL... hy-droxyl-al-kyla-mine. (a) Chemical substance and significant new uses subject to reporting. (1) The...

A validated UPLC-MS/MS method for the analysis of linezolid and a novel oxazolidinone derivative (PH027) in plasma and its application to tissue distribution study in rabbits.

PubMed

Hedaya, Mohsen A; Thomas, Vidhya; Abdel-Hamid, Mohamed E; Kehinde, Elijah O; Phillips, Oludotun A

2017-01-01

Linezolid is the first approved oxazolidinone antibacterial agent, whereas PH027 is a novel compound of the same class that exhibits good in vitro antibacterial activity. The objective of this study was to develop an UPLC-MS/MS assay for the analysis of linezolid and PH027 in plasma and to apply the method for comparative pharmacokinetic and tissue distribution studies of both compounds. Plasma samples and calibrators were extracted with diethyl ether after addition of the internal standard solution. After evaporation of the ether layer, the residue was reconstituted in mobile phase and injected into UPLC-MS/MS. The mobile phase consisted of 2mM ammonium acetate buffer solution and acetonitrile (70:30) at a flow rate of 0.2ml/min. Separation was achieved using UPLC BEH C 18 column, and quantitative determination of the analytes was performed using multiple-reaction monitoring (MRM) scanning mode. The method was validated by analyzing quality control tissue homogenate samples, and was applied to analyze tissue homogenate samples obtained following IV injections of linezolid and PH027 in rabbits. The developed UPLC-MS/MS method was linear in the concentration range of 50-5000ng/ml. Validation of the method proved that the method's precision, selectivity and stability were all within the acceptable limits. Linezolid and PH027 concentrations were accurately determined in the quality control tissue homogenate samples, and analysis of samples obtained following IV administration of the two compounds showed that the tissue to plasma concentration ratio of PH027 was higher than that of linezolid probably due to its higher lipophilicity. The developed UPLC-MS/MS method for the analysis of linezolid and PH027 in rabbit's plasma can accurately determine the concentrations of these compounds in different tissues. Copyright © 2016 Elsevier B.V. All rights reserved.

Protective effects of sweet orange (Citrus sinensis) peel and their bioactive compounds on oxidative stress.

PubMed

Chen, Zong-Tsi; Chu, Heuy-Ling; Chyau, Charng-Cherng; Chu, Chin-Chen; Duh, Pin-Der

2012-12-15

Protective effects of sweet orange (Citrus sinensis) peel and their bioactive compounds on oxidative stress were investigated. According to HPLC-DAD and HPLC-MS/MS analysis, hesperidin (HD), hesperetin (HT), nobiletin (NT), and tangeretin (TT) were present in water extracts of sweet orange peel (WESP). The cytotoxic effect in 0.2mM t-BHP-induced HepG2 cells was inhibited by WESP and their bioactive compounds. The protective effect of WESP and their bioactive compounds in 0.2mM t-BHP-induced HepG2 cells may be associated with positive regulation of GSH levels and antioxidant enzymes, decrease in ROS formation and TBARS generation, increase in the mitochondria membrane potential and Bcl-2/Bax ratio, as well as decrease in caspase-3 activation. Overall, WESP displayed a significant cytoprotective effect against oxidative stress, which may be most likely because of the phenolics-related bioactive compounds in WESP, leading to maintenance of the normal redox status of cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Modeling of Complex Mixtures: JP-8 Toxicokinetics

DTIC Science & Technology

2008-10-01

generic tissue compartments in which we have combined diffusion limitation and deep tissue (global tissue model). We also applied a QSAR approach for...SUBJECT TERMS jet fuel, JP-8, PBPK modeling, complex mixtures, nonane, decane, naphthalene, QSAR , alternative fuels 16. SECURITY CLASSIFICATION OF...necessary, to apply to the interaction of specific compounds with specific tissues. We have also applied a QSAR approach for estimating blood and tissue

Water-quality assessment of the Potomac River Basin: analysis of available pesticide data, 1972-1990

USGS Publications Warehouse

Zappia, Humbert; Fisher, Gary T.

1997-01-01

A study of available data for the period from 1972 to 1990 was conducted to characterize the occurrence and distribution of pesticides in sur-face water, bottom material, ground water, and fish tissue in the Potomac River Basin. The study was conducted by the Potomac River study unit of the U.S. Geological Survey?s National Water-Quality Assessment (NAWQA) program. Exist-ing data coverage was evaluated to guide future data-collection activities. Data from computer data bases and from published and unpublished reports were obtained from local, State, and Fed-eral agencies in the four Potomac River Basin states and the District of Columbia. Data are available for all environmental media, but geo-graphic and temporal coverage are limited. Clusters of data occur in the north-central parts of the basin, with numerous samples at discrete loca-tions in the Shenandoah and Monocacy River Basins, along the mainstem Potomac River, in the Washington, D.C., area, and in streams along the Potomac Estuary. Much of the available surface-water and bottom-material data are from the ear-lier years of the period of interest, the ground-water data are from the middle years, and the fish-tissue data are distributed over much of the period. Overall, temporal coverage is not sufficient for analysis of trends. Comparisons between different sample media are possible in some areas of the Potomac River Basin, particularly in the northern end of the Great Valley. Residual concentrations of some pesticides have been found in surface water, bottom mate-rial, ground water, and fish tissue. Samples have been analyzed for a total of at least 69 pesticides and related compounds in surface water, bottom material, ground water, and fish tissue. Most con-centrations of the pesticides analyzed during the period from 1972 to 1990 were less than or equal to reporting limits. For surface-water samples, 13 out of 41 pes-ticides and related compounds analyzed had concentrations equal to or greater than the report-ing limits. Compounds reported in surface water included 2,4-D, atrazine, aldrin, chlordane, DDT and related compounds, dieldrin, endrin, lindane, prometone, prometryne, and simazine. For bottom material samples, 19 of 31 pesticides and related compounds analyzed had concentrations equal to or greater than the reporting limits. Compounds reported in bottom material included aldrin, chlor-dane, DDT and related compounds, diazinon, dieldrin, endosulfan, endrin, ethion, heptachlor, heptachlor epoxide, lindane, parathion, and tox-aphene. In ground-water samples, 14 of 39 pesticides and related compounds analyzed had concentrations equal to or greater than the report-ing limits. Compounds reported in ground water included 2,4-D, atrazine, chlordane, cyanazine, DDT and related compounds, diazinon, dieldrin, endosulfan, endrin, heptachlor epoxide, malathion, methyl parathion, simazine. For fish- tissue sam-ples, 30 of the 37 pesticides and related compounds analyzed had concentrations equal to or greater than the reporting limits. Compounds reported included aldrin, chlorpyrifos, dacthal, dieldrin, endrin, HCB, heptachlor, heptachlor epoxide, methoxychlor, mirex, PCA, toxaphene, and those compounds related to chlordane, DDT, and lindane.

Suppression of AMF/PGI-mediated tumorigenic activities by ursolic acid in cultured hepatoma cells and in a mouse model.

PubMed

Shih, Wen-Ling; Yu, Feng-Ling; Chang, Ching-Dong; Liao, Ming-Huei; Wu, Hung-Yi; Lin, Ping-Yuan

2013-10-01

Our previous studies demonstrated that autocrine motility factor/phosphoglucose isomerase (AMF/PGI) possesses tumorigenic activities through the modulation of intracellular signaling. We then investigated the effects of ursolic acid (UA), oleanolic acid (OA), tangeretin, and nobiletin against AMF/PGI-mediated oncogenesis in cultured stable Huh7 and Hep3B cells expressing wild-type or mutated AMF/PGI and in a mouse model in this study. The working concentrations of the tested compounds were lower than their IC10 , which was determined by Brdu incorporation and colony formation assay. Only UA efficiently suppressed the AMF/PGI-induced Huh7 cell migration and MMP-3 secretion. Additionally, UA inhibited the AMF/PGI-mediated protection against TGF-β-induced apoptosis in Hep3B cells, whereas OA, tangeretin, and nobiletin had no effect. In Huh7 cells and tumor tissues, UA disrupted the Src/RhoA/PI 3-kinase signaling and complex formation induced by AMF/PGI. In the Hep3B system, UA dramatically suppressed AMF/PGI-induced anti-apoptotic signaling transmission, including Akt, p85, Bad, and Stat3 phosphorylation. AMF/PGI enhances tumor growth, angiogenesis, and pulmonary metastasis in mice, which is correlated with its enzymatic activity, and critically, UA intraperitoneal injection reduces the tumorigenesis in vivo, enhances apoptosis in tumor tissues and also prolongs mouse survival. Combination of sub-optimal dose of UA and cisplatin, a synergistic tumor cell-killing effects was found. Thus, UA modulates intracellular signaling and might serve as a functional natural compound for preventing or alleviating hepatocellular carcinoma. © 2012 Wiley Periodicals, Inc.

Environmental monitoring of brominated flame retardants

NASA Astrophysics Data System (ADS)

Vagula, Mary C.; Kubeldis, Nathan; Nelatury, Charles F.

2011-06-01

Brominated flame retardants (BFRs) are synthetic organobromide compounds which inhibit ignition and combustion processes. Because of their immense ability to retard fire and save life and property, they have been extensively used in many products such as TVs, computers, foam, plastics etc. The five major classes of BFRs are tetrabromobisphenol-A (TBBPA), hexabromocyclododecane (HBCD), pentabromodiphenyl ether, octabromodiphenyl ether, and decabromodiphenyl ether. The last three are also commonly called PBDEs. BDE-85 and BDE-209 are the two prominent congeners of PBDEs and this study reports the adverse effects of these congeners in rodents. Exposure of rat sciatic nerves to 5 μg/mL and 20 μg/mL of BDE-85 and BDE-209 respectively lead to significant, concentration dependent reduction in nerve conduction function. Glucose absorption in the rat intestinal segments exposed to 5 μg/mL of BDE-85 and BDE-209 was significantly reduced for both the compounds tested. Lastly, mice when exposed to 0.25 mg/kg body weight for four days showed a disruption in oxidant and antioxidant equilibrium. The tissues namely liver and brain have shown increase in the levels of lipid hydroperoxides indicating oxidative stress. Moreover, all the protective enzymes namely superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, and glutathione S transferase (GST) have shown tissue specific alterations indicating the induction of damaging oxidative stress and setting in of lipid peroxidation in exposed animals. The results indicate monitoring of PBDEs in the environment is essential because levels as low as 5 μg/mL and 0.25 mg/kg body weight were able to cause damage to the functions of rodents.

Potent Phototoxicity of Marine Bunker Oil to Translucent Herring Embryos after Prolonged Weathering

PubMed Central

Incardona, John P.; Vines, Carol A.; Linbo, Tiffany L.; Myers, Mark S.; Sloan, Catherine A.; Anulacion, Bernadita F.; Boyd, Daryle; Collier, Tracy K.; Morgan, Steven; Cherr, Gary N.; Scholz, Nathaniel L.

2012-01-01

Pacific herring embryos (Clupea pallasi) spawned three months following the Cosco Busan bunker oil spill in San Francisco Bay showed high rates of late embryonic mortality in the intertidal zone at oiled sites. Dead embryos developed to the hatching stage (e.g. fully pigmented eyes) before suffering extensive tissue deterioration. In contrast, embryos incubated subtidally at oiled sites showed evidence of sublethal oil exposure (petroleum-induced cardiac toxicity) with very low rates of mortality. These field findings suggested an enhancement of oil toxicity through an interaction between oil and another environmental stressor in the intertidal zone, such as higher levels of sunlight-derived ultraviolet (UV) radiation. We tested this hypothesis by exposing herring embryos to both trace levels of weathered Cosco Busan bunker oil and sunlight, with and without protection from UV radiation. Cosco Busan oil and UV co-exposure were both necessary and sufficient to induce an acutely lethal necrotic syndrome in hatching stage embryos that closely mimicked the condition of dead embryos sampled from oiled sites. Tissue levels of known phototoxic polycyclic aromatic compounds were too low to explain the observed degree of phototoxicity, indicating the presence of other unidentified or unmeasured phototoxic compounds derived from bunker oil. These findings provide a parsimonious explanation for the unexpectedly high losses of intertidal herring spawn following the Cosco Busan spill. The chemical composition and associated toxicity of bunker oils should be more thoroughly evaluated to better understand and anticipate the ecological impacts of vessel-derived spills associated with an expanding global transportation network. PMID:22312421

Red wine alcohol promotes quercetin absorption and directs its metabolism towards isorhamnetin and tamarixetin in rat intestine in vitro.

PubMed

Dragoni, Stefania; Gee, Jennifer; Bennett, Richard; Valoti, Massimo; Sgaragli, Giampietro

2006-04-01

Moderate consumption of red wine has been associated with beneficial effects on human health, and this has been attributed to the flavonoid content. Factors that influence the bioavailability of this group of polyphenolic compounds are therefore important. Using the rat cannulated everted jejunal sac technique, we have investigated the effect of alcohol on the intestinal absorption of quercetin and its 3-O-glucoside from red wine. Tissue preparations were incubated in whole or dealcoholised red wine, diluted 1 : 1 with Krebs buffer for 20 min at 37 degrees C, after which the mucosa was removed and processed for HPLC analysis. Tissues exposed to red wine had significantly higher amounts of both quercetin (x 3; P < 0.001) and quercetin-3-O-glucoside (x 1.5; P < 0.01) associated with them, compared with sacs incubated in the dealcoholised equivalent. In addition, both tamarixetin (T) and isorhamnetin (I), in the mucosal tissue from sacs exposed to the whole wine, were significantly elevated approximately two fold (P < 0.05; P < 0.01, respectively). Similar results were obtained when sacs were incubated in Krebs buffer containing a mixture of pure quercetin and quercetin-3-O-glucoside with or without alcohol, and, although effects on the apparent absorption of Q and Q-3-G were not so marked, concentrations of the metabolites quercetin-3-O-glucuronide and I were significantly increased by the presence of alcohol (P < 0.01 and P < 0.001, respectively). It is therefore plausible that the moderate alcohol content of red wine contributes to its beneficial health effects in humans by both increasing the absorption of quercetin and quercetin-3-O-glucoside and by channelling their metabolism towards O-methylation to yield compounds (T and I), which have potential protective effects against cancer and cardiovascular diseases.

Red wine alcohol promotes quercetin absorption and directs its metabolism towards isorhamnetin and tamarixetin in rat intestine in vitro

PubMed Central

Dragoni, Stefania; Gee, Jennifer; Bennett, Richard; Valoti, Massimo; Sgaragli, Giampietro

2006-01-01

Moderate consumption of red wine has been associated with beneficial effects on human health, and this has been attributed to the flavonoid content. Factors that influence the bioavailability of this group of polyphenolic compounds are therefore important. Using the rat cannulated everted jejunal sac technique, we have investigated the effect of alcohol on the intestinal absorption of quercetin and its 3-O-glucoside from red wine. Tissue preparations were incubated in whole or dealcoholised red wine, diluted 1 : 1 with Krebs buffer for 20 min at 37°C, after which the mucosa was removed and processed for HPLC analysis. Tissues exposed to red wine had significantly higher amounts of both quercetin (× 3; P<0.001) and quercetin-3-O-glucoside (× 1.5; P<0.01) associated with them, compared with sacs incubated in the dealcoholised equivalent. In addition, both tamarixetin (T) and isorhamnetin (I), in the mucosal tissue from sacs exposed to the whole wine, were significantly elevated approximately two fold (P<0.05; P<0.01, respectively). Similar results were obtained when sacs were incubated in Krebs buffer containing a mixture of pure quercetin and quercetin-3-O-glucoside with or without alcohol, and, although effects on the apparent absorption of Q and Q-3-G were not so marked, concentrations of the metabolites quercetin-3-O-glucuronide and I were significantly increased by the presence of alcohol (P<0.01 and P<0.001, respectively). It is therefore plausible that the moderate alcohol content of red wine contributes to its beneficial health effects in humans by both increasing the absorption of quercetin and quercetin-3-O-glucoside and by channelling their metabolism towards O-methylation to yield compounds (T and I), which have potential protective effects against cancer and cardiovascular diseases. PMID:16444288

Structural and metabolic changes in rhizophores of the Cerrado species Chrysolaena obovata (Less.) Dematt. as influenced by drought and re-watering

PubMed Central

Garcia, Paola M. A.; Hayashi, Adriana H.; Silva, Emerson A.; Figueiredo-Ribeiro, Rita de Cássia L.; Carvalho, Maria A. M.

2015-01-01

The high fructan contents in underground organs of Cerrado species, high water solubility, and fast metabolism of these compounds highlight their role as carbon storage and as an adaptive feature in plants under drought. In this study, we showed that anatomical structure, in association with soluble compounds and metabolism of inulin-type fructans were modified in rhizophores of Crysolaena obovata submitted to water suppression and recovery after re-watering. Plants were subjected to daily watering (control), suppression of watering for 22 days (water suppression) and suppression of watering followed by re-watering after 10 days (re-watered). Plants were collected at time 0 and after 3, 7, 10, 12, 17, and 22 days of treatment. In addition to changes in fructan metabolism, high proline content was detected in drought stressed plants, contributing to osmoregulation and recovery after water status reestablishment. Under water suppression, total inulin was reduced from approx. 60 to 40%, mainly due to exohydrolase activity. Concurrently, the activity of fructosyltransferases promoted the production of short chain inulin, which could contribute to the increase in osmotic potential. After re-watering, most parameters analyzed were similar to those of control plants, indicating the resumption of regular metabolism, after water absorption. Inulin sphero-crystals accumulated in parenchymatic cells of the cortex, vascular tissues and pith were reduced under drought and accompanied anatomical changes, starting from day 10. At 22 days of drought, the cortical and vascular tissues were collapsed, and inulin sphero-crystals and inulin content were reduced. The localization of inulin sphero-crystals in vascular tissues of C. obovata, as well as the decrease of total inulin and the increase in oligo:polysaccharide ratio in water stressed plants is consistent with the role of fructans in protecting plants against drought. PMID:26442035

In vitro and in vivo studies on antitumor effects of gossypol on human stomach adenocarcinoma (AGS) cell line and MNNG induced experimental gastric cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gunassekaran, G.R., E-mail: gunassekaran@yahoo.co.in; Kalpana Deepa Priya, D.; Gayathri, R.

2011-08-12

Highlights: {yields} Gossypol is a well known polyphenolic compound used for anticancer studies but we are the first to report that gossypol has antitumor effect on MNNG induced gastric cancer in experimental animal models. {yields} Our study shows that gossypol inhibits the proliferation of AGS (human gastric adenocarcinoma) cell line. {yields} In animal models, gossypol extends the survival of cancer bearing animals and also protects the cells from carcinogenic effect. {yields} So we suggest that gossypol would be a potential chemotherapeutic and chemopreventive agent for gastric cancer. -- Abstract: The present study has evaluated the chemopreventive effects of gossypol onmore » N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis and on human gastric adenocarcinoma (AGS) cell line. Gossypol, C{sub 30}H{sub 30}O{sub 8}, is a polyphenolic compound that has anti proliferative effect and induces apoptosis in various cancer cells. The aim of this work was to delineate in vivo and in vitro anti-initiating mechanisms of orally administered gossypol in target (stomach) tissues and in human gastric adenocarcinoma (AGS) cell line. In vitro results prove that gossypol has potent cytotoxic effect and inhibit the proliferation of adenocarcinoma (AGS) cell line. In vivo results prove gossypol to be successful in prolonging the survival of MNNG induced cancer bearing animals and in delaying the onset of tumor in animals administrated with gossypol and MNNG simultaneously. Examination of the target (stomach) tissues in sacrificed experimental animals shows that administration of gossypol significantly reduces the level of tumor marker enzyme (carcino embryonic antigen) and pepsin. The level of Nucleic acid contents (DNA and RNA) significantly reduces, and the membrane damage of glycoprotein subsides, in the target tissues of cancer bearing animals, with the administration of gossypol. These data suggest that gossypol may create a beneficial effect in patients with gastric cancer.« less

A comparative study of three tissue-cultured Dendrobium species and their wild correspondences by headspace gas chromatography-mass spectrometry combined with chemometric methods.

PubMed

Chen, Nai-Dong; You, Tao; Li, Jun; Bai, Li-Tao; Hao, Jing-Wen; Xu, Xiao-Yuan

2016-10-01

Plant tissue culture technique is widely used in the conservation and utilization of rare and endangered medicinal plants and it is crucial for tissue culture stocks to obtain the ability to produce similar bioactive components as their wild correspondences. In this paper, a headspace gas chromatography-mass spectrometry method combined with chemometric methods was applied to analyze and evaluate the volatile compounds in tissue-cultured and wild Dendrobium huoshanense Cheng and Tang, Dendrobium officinale Kimura et Migo and Dendrobium moniliforme (Linn.) Sw. In total, 63 volatile compounds were separated, with 53 being identified from the three Dendrobium spp. Different provenances of Dendrobiums had characteristic chemicals and showed remarkable quantity discrepancy of common compositions. The similarity evaluation disclosed that the accumulation of volatile compounds in Dendrobium samples might be affected by their provenance. Principal component analysis showed that the first three components explained 85.9% of data variance, demonstrating a good discrimination between samples. Gas chromatography-mass spectrometry techniques, combined with chemometrics, might be an effective strategy for identifying the species and their provenance, especially in the assessment of tissue-cultured Dendrobium quality for use in raw herbal medicines. Copyright © 2016. Published by Elsevier B.V.

40 CFR 721.775 - Brominated aromatic com-pound (generic name).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Brominated aromatic com-pound (generic... Specific Chemical Substances § 721.775 Brominated aromatic com-pound (generic name). (a) Chemical... as a brominated aromatic compound (PMN P-84-824) is subject to reporting under this section for the...

40 CFR 721.9668 - Organotin lithium compound.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Organotin lithium compound. 721.9668... Substances § 721.9668 Organotin lithium compound. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as an organotin lithium compound (PMN P-93-1119...

40 CFR 721.9668 - Organotin lithium compound.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Organotin lithium compound. 721.9668... Substances § 721.9668 Organotin lithium compound. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as an organotin lithium compound (PMN P-93-1119...

40 CFR 721.9668 - Organotin lithium compound.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Organotin lithium compound. 721.9668... Substances § 721.9668 Organotin lithium compound. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as an organotin lithium compound (PMN P-93-1119...

40 CFR 721.9668 - Organotin lithium compound.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Organotin lithium compound. 721.9668... Substances § 721.9668 Organotin lithium compound. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as an organotin lithium compound (PMN P-93-1119...

40 CFR 721.9668 - Organotin lithium compound.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Organotin lithium compound. 721.9668... Substances § 721.9668 Organotin lithium compound. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance generically identified as an organotin lithium compound (PMN P-93-1119...

IL-33 induces protective effects in adipose tissue inflammation during obesity in mice

PubMed Central

Miller, Ashley M.; Asquith, Darren L.; Hueber, Axel J.; Anderson, Lesley A.; Holmes, William M.; McKenzie, Andrew N.; Xu, Damo; Sattar, Naveed; McInnes, Iain B.; Liew, Foo Y.

2014-01-01

Rationale Chronic low-grade inflammation involving adipose tissue likely contributes to the metabolic consequences of obesity. The cytokine IL-33 and its receptor ST2 are expressed in adipose tissue but their role in adipose tissue inflammation during obesity is unclear. Objective To examine the functional role of IL-33 in adipose tissues, and investigate the effects on adipose tissue inflammation and obesity in vivo. Methods and Results We demonstrate that treatment of adipose tissue cultures in vitro with IL-33 induced production of Th2 cytokines (IL-5, IL-13, IL-10), and reduced expression of adipogenic and metabolic genes. Administration of recombinant IL-33 to genetically obese diabetic (ob/ob) mice led to reduced adiposity, reduced fasting glucose and improved glucose and insulin tolerance. IL-33 also induced accumulation of Th2 cells in adipose tissue and polarization of adipose tissue macrophages towards an M2 alternatively activated phenotype (CD206+), a lineage associated with protection against obesity-related metabolic events. Furthermore, mice lacking endogenous ST2 fed HFD had increased body weight and fat mass, impaired insulin secretion and glucose regulation compared to WT controls fed HFD. Conclusions In conclusion, IL-33 may play a protective role in the development of adipose tissue inflammation during obesity. PMID:20634488

Enhancing glutamate transport: mechanism of action of Parawixin1, a neuroprotective compound from Parawixia bistriata spider venom.

PubMed

Fontana, Andréia Cristina Karklin; de Oliveira Beleboni, Renê; Wojewodzic, Marcin Wlodzimierz; Ferreira Dos Santos, Wagner; Coutinho-Netto, Joaquim; Grutle, Nina Julie; Watts, Spencer D; Danbolt, Niels Christian; Amara, Susan G

2007-11-01

Previous studies have shown that a compound purified from the spider Parawixia bistriata venom stimulates the activity of glial glutamate transporters and can protect retinal tissue from ischemic damage. To understand the mechanism by which this compound enhances transport, we examined its effects on the functional properties of glutamate transporters after solubilization and reconstitution in liposomes and in transfected COS-7 cells. Here, we demonstrate in both systems that Parawixin1 promotes a direct and selective enhancement of glutamate influx by the EAAT2 transporter subtype through a mechanism that does not alter the apparent affinities for the cosubstrates glutamate or sodium. In liposomes, we observed maximal enhancement by Parawixin1 when extracellular sodium and intracellular potassium concentrations are within physiological ranges. Moreover, the compound does not enhance the reverse transport of glutamate under ionic conditions that favor efflux, when extracellular potassium is elevated and the sodium gradient is reduced, nor does it alter the exchange of glutamate in the absence of internal potassium. These observations suggest that Parawixin1 facilitates the reorientation of the potassium-bound transporter, the rate-limiting step in the transport cycle, a conclusion further supported by experiments showing that Parawixin1 does not stimulate uptake by an EAAT2 transport mutant (E405D) defective in the potassium-dependent reorientation step. Thus, Parawixin1 enhances transport through a novel mechanism targeting a step in the transport cycle distinct from substrate influx or efflux and provides a basis for the design of new drugs that act allosterically on transporters to increase glutamate clearance.

Permeability of the hard tissue bridge formed after pulpotomy with calcium hydroxide: a histologic study.

PubMed

Holland, R; de Souza, V; de Mello, W; Nery, M J; Bernabé, P F; Otoboni Filho, J A

1979-09-01

Analysis of these results shows that complete hard tissue bridges, aside from occurring with great frequency, produce a satisfactory protection to the pulp. In a case in which the barrier is incomplete, some future clinical problems may result as an incomplete barrier does not offer adequate protection as shown by the chronic inflammatory reaction in the remaining pulp tissue.

PROTECTION OF THE EMBRYO AGAINST THE CONGENITAL AND LETHAL EFFECTS OF X- IRRADIATION. PART I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rugh, R.; Grupp, E.

1960-04-01

The effects of 15 agents, some given before and some after x irradiation to 200 r, have been studied for their effectiveness in protecting the 8.5-day mouse embryo against embryonic or fetal death and the development of the severe cephalic congenital anomaly known as exencephalia (or brain hernia). Some 4979 fetuses were examined. Of the agents studied, only cysteinamine, cystamine, and anoxia proved to be statistically "protective" at all. Cysteinamine and cystamine (both -SH compounds) given I.P. before x irradiation to 200 r allowed 73 to 80% of the 8.5-day embryos to survive to term while the untreated but irradiatedmore » control litters had a survival of only 41%. Funther, there was considerable reduction in bcth uterine death and the congenital anomaly of exencephalia. Anoxia (6% O/sub 2/ + 94% N/sub 2/) aIlowed 71% to come through as ""apparently normal," an increase of 30% over the unprotected irradiated controls. Whether there is long-term damage to the 8.5day embryo from the temporary anoxia alone has not been determined, although the anoxic controls showed 96% " apparently nornnal." Distilled water given I.P. before irradiation, making the milieu of the embryos hypotonic, appeared to be deleterious, causing 2% exencephalia even without x irradiation. When combined with x rays, distilled water reduced the "apparentiy normals" to 31%, or 10% lower than with irradiation alone. Saline in various concentrations was not protective. None of the tissue homogenates (spleen, marrow, liver, or brain of a homologous newborn source) proved to be of any protective value. It is suggested that the protective element in such tissue homogenates may be cellular since the placenta acts as the most efficient filter to allow only the dialyzable substances through to the embryo. However, the fact that the 8.5-day mouse embryo has not yet developed its hematopoietic syatem may explain the failure of homogenates which seem to protect through hematopoietic regeneration. Hypoxia from hypoglycemia following insulin injection was not protective. Insulin or dextrose or the two in combination were -not panticularly harraful to the 8.5-day mouse embryo but when combined with x irradiation were very damaging. "Protection" as used in this study is statistical and relates to the percentage changes in ""apparently normal" fetuses, resorptions, deaths, and congenital anomalies. It does not imply that the surviving mice are without irradiation sequelae. In fact many of the "apparently normals" have eye defects and this might well reveal other and more subtle C. N. 8. damage. On the basis of survival, however, cysteinamine, cystamine, and anoxia did afford some protection. (auth)« less

Renal targeting potential of a polymeric drug carrier, poly-l-glutamic acid, in normal and diabetic rats.

PubMed

Chai, Hann-Juang; Kiew, Lik-Voon; Chin, Yunni; Norazit, Anwar; Mohd Noor, Suzita; Lo, Yoke-Lin; Looi, Chung-Yeng; Lau, Yeh-Siang; Lim, Tuck-Meng; Wong, Won-Fen; Abdullah, Nor Azizan; Abdul Sattar, Munavvar Zubaid; Johns, Edward J; Chik, Zamri; Chung, Lip-Yong

2017-01-01

Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier. 3 H-deoxycytidine-labeled PGs (17 or 41 kDa) and 3 H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido) fluorescein (fluoresceinyl glycine amide)-labeled PG (PG-AF). To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF). In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr) presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal accumulation than the free radiolabel after 24 h post injection. The accumulation of PG-AF was primarily found in the renal tubular tissues at 2 and 6 h after an intravenous administration. In the diabetic (oxidative stress-induced) kidneys, 41 kDa PG-Tr showed the greatest renal accumulation of 8-fold higher than the free compound 24 h post dose. Meanwhile, the synthesized PG-AEBSF was found to inhibit intracellular nicotinamide adenine dinucleotide phosphate oxidase (a reactive oxygen species generator) at an efficiency that is comparable to that of free AEBSF. This indicates the preservation of the anti-oxidative stress properties of AEBSF in the conjugated state. The favorable accumulation property of 41 kDa PG in normal and oxidative stress-induced kidneys, along with its capabilities in conserving the pharmacological properties of the conjugated renal protective drugs, supports its role as a potential renal targeting drug carrier.

Renal targeting potential of a polymeric drug carrier, poly-l-glutamic acid, in normal and diabetic rats

PubMed Central

Chai, Hann-Juang; Kiew, Lik-Voon; Chin, Yunni; Norazit, Anwar; Mohd Noor, Suzita; Lo, Yoke-Lin; Looi, Chung-Yeng; Lau, Yeh-Siang; Lim, Tuck-Meng; Wong, Won-Fen; Abdullah, Nor Azizan; Abdul Sattar, Munavvar Zubaid; Johns, Edward J; Chik, Zamri; Chung, Lip-Yong

2017-01-01

Background and purpose Poly-l-glutamic acid (PG) has been used widely as a carrier to deliver anticancer chemotherapeutics. This study evaluates PG as a selective renal drug carrier. Experimental approach 3H-deoxycytidine-labeled PGs (17 or 41 kDa) and 3H-deoxycytidine were administered intravenously to normal rats and streptozotocin-induced diabetic rats. The biodistribution of these compounds was determined over 24 h. Accumulation of PG in normal kidneys was also tracked using 5-(aminoacetamido) fluorescein (fluoresceinyl glycine amide)-labeled PG (PG-AF). To evaluate the potential of PGs in ferrying renal protective anti-oxidative stress compounds, the model drug 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) was conjugated to 41 kDa PG to form PG-AEBSF. PG-AEBSF was then characterized and evaluated for intracellular anti-oxidative stress efficacy (relative to free AEBSF). Results In the normal rat kidneys, 17 kDa radiolabeled PG (PG-Tr) presents a 7-fold higher, while 41 kDa PG-Tr shows a 15-fold higher renal accumulation than the free radiolabel after 24 h post injection. The accumulation of PG-AF was primarily found in the renal tubular tissues at 2 and 6 h after an intravenous administration. In the diabetic (oxidative stress-induced) kidneys, 41 kDa PG-Tr showed the greatest renal accumulation of 8-fold higher than the free compound 24 h post dose. Meanwhile, the synthesized PG-AEBSF was found to inhibit intracellular nicotinamide adenine dinucleotide phosphate oxidase (a reactive oxygen species generator) at an efficiency that is comparable to that of free AEBSF. This indicates the preservation of the anti-oxidative stress properties of AEBSF in the conjugated state. Conclusion/Implications The favorable accumulation property of 41 kDa PG in normal and oxidative stress-induced kidneys, along with its capabilities in conserving the pharmacological properties of the conjugated renal protective drugs, supports its role as a potential renal targeting drug carrier. PMID:28144140

Factors Affecting the Extraction of Intact Ribonucleic Acid from Plant Tissues Containing Interfering Phenolic Compounds

PubMed Central

Newbury, H. John; Possingham, John V.

1977-01-01

Using conventional methods it is impossible to extract RNA as uncomplexed intact molecules from the leaves of grapevines (Vitis vinifera L.) and from a number of woody perennial species that contain high levels of reactive phenolic compounds. A procedure involving the use of high concentrations of the chaotropic agent sodium perchlorate prevents the binding of phenolic compounds to RNA during extraction. Analyses of the phenolics present in plant tissues used in these experiments indicate that there is a poor correlation between the total phenolic content and the complexing of RNA. However, qualitative analyses suggest that proanthocyanidins are involved in the tanning of RNA during conventional extractions. PMID:16660134

New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models.

PubMed

Schur, Rebecca M; Gao, Songqi; Yu, Guanping; Chen, Yu; Maeda, Akiko; Palczewski, Krzysztof; Lu, Zheng-Rong

2018-01-24

No clinically approved therapies are currently available that prevent the onset of photoreceptor death in retinal degeneration. Signaling between retinal neurons is regulated by the release and uptake of neurotransmitters, wherein GABA is the main inhibitory neurotransmitter. In this work, novel 3-chloropropiophenone derivatives and the clinical anticonvulsants tiagabine and vigabatrin were tested to modulate GABA signaling and protect against light-induced retinal degeneration. Abca4 -/- Rdh8 -/- mice, an accelerated model of retinal degeneration, were exposed to intense light after prophylactic injections of one of these compounds. Imaging and functional assessments of the retina indicated that these compounds successfully protected photoreceptor cells from degeneration to maintain a full-visual-field response. Furthermore, these compounds demonstrated a strong safety profile in wild-type mice and did not compromise visual function or damage the retina, despite repeated administration. These results indicate that modulating inhibitory GABA signaling can offer prophylactic protection against light-induced retinal degeneration.-Schur, R. M., Gao, S., Yu, G., Chen, Y., Maeda, A., Palczewski, K., Lu, Z.-R. New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models.

Compound 9a, a novel synthetic histone deacetylase inhibitor, protects against septic injury in mice by suppressing MAPK signalling

PubMed Central

Kim, So‐Jin; Baek, Ki Seon; Park, Hyun‐Ju; Jung, Young Hoon

2016-01-01

Background and Purpose Sepsis is a life‐threatening clinical condition characterized by uncontrolled inflammatory responses and is a major cause of death in intensive care units. Histone deacetylase (HDAC) inhibitors have recently exhibited anti‐inflammatory properties. MAPK phosphatase (MKP) suppresses MAPK signalling, which plays an important role in inflammatory responses. The purpose of this study was to investigate the protective mechanisms of Compound 9a, a newly synthetized HDAC inhibitor, against septic injury. Experimental Approach The anti‐inflammatory properties of Compound 9a were assayed in LPS‐stimulated RAW264.7 cells. In vivo, polymicrobial sepsis was induced in C57BL/6 mice by caecal ligation and puncture (CLP). The mice were treated with Compound 9a (i.p., 10 mg∙kg−1) 2 h before and immediately after CLP. Key Results Compound 9a inhibited the increased production of TNF‐α, IL‐6 and NO in LPS‐stimulated RAW264.7 cells. In mice with CLP, Compound 9a improved survival rate, attenuated organ injuries and decreased serum TNF‐α and IL‐6 levels. CLP increased expression of toll‐like receptor 4, phosphorylated (p)‐p38, p‐JNK and p‐ERK proteins, which was attenuated by Compound 9a. Compound 9a decreased MKP‐1 association with HDAC1 and enhanced MKP‐1 acetylation and enhanced MKP‐1 association with p‐p38 and p‐ERK. Moreover, the inhibitory effects of Compound 9a on serum cytokine levels and phosphorylation of MAPK were abolished by MKP‐1 siRNA. Conclusions and Implications Our findings suggest that Compound 9a protected against septic injury by suppressing MAPK‐mediated inflammatory signalling. PMID:26689981

Iron from nanocompounds containing iron and zinc is highly bioavailable in rats without tissue accumulation

NASA Astrophysics Data System (ADS)

Hilty, Florentine M.; Arnold, Myrtha; Hilbe, Monika; Teleki, Alexandra; Knijnenburg, Jesper T. N.; Ehrensperger, Felix; Hurrell, Richard F.; Pratsinis, Sotiris E.; Langhans, Wolfgang; Zimmermann, Michael B.

2010-05-01

Effective iron fortification of foods is difficult, because water-soluble compounds that are well absorbed, such as ferrous sulphate (FeSO4), often cause unacceptable changes in the colour or taste of foods. Poorly water-soluble compounds, on the other hand, cause fewer sensory changes, but are not well absorbed. Here, we show that poorly water-soluble nanosized Fe and Fe/Zn compounds (specific surface area ~190 m2 g-1) made by scalable flame aerosol technology have in vivo iron bioavailability in rats comparable to FeSO4 and cause less colour change in reactive food matrices than conventional iron fortificants. The addition of Zn to FePO4 and Mg to Fe/Zn oxide increases Fe absorption from the compounds, and doping with Mg also improves their colour. After feeding rats with nanostructured iron-containing compounds, no stainable Fe was detected in their gut wall, gut-associated lymphatics or other tissues, suggesting no adverse effects. Nanosizing of poorly water-soluble Fe compounds sharply increases their absorption and nutritional value.

Synthesis and Anticancer Activity of 3-(Substituted Aroyl)-4-(3,4,5-trimethoxyphenyl)-1H-pyrrole Derivatives.

PubMed

Zhan, Xiao-Ping; Lan, Lan; Wang, Shuai; Zhao, Kai; Xin, Yu-Xuan; Qi, Qi; Wang, Yao-Lin; Mao, Zhen-Min

2017-02-01

A series of 3-(substituted aroyl)-4-(3,4,5-trimethoxyphenyl)-1H-pyrrole derivatives were synthesized and determined for their anticancer activity against eleven cancer cell lines and two normal tissue cell lines using MTT assay. Among the synthesized compounds, compound 3f was the most potent compound against A375, CT-26, HeLa, MGC80-3, NCI-H460 and SGC-7901 cells (IC 50  = 8.2 - 31.7 μm); 3g, 3n and 3a were the most potent compounds against CHO (IC 50  = 8.2 μm), HCT-15 (IC 50  = 21 μm) and MCF-7 cells (IC 50  = 18.7 μm), respectively. Importantly, all the target compounds showed no cytotoxicity towards the normal tissue cell (IC 50  > 100 μm). Thus, these compounds with the potent anticancer activity and low toxicity have potential for the development of new anticancer chemotherapy agents. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Iron from nanocompounds containing iron and zinc is highly bioavailable in rats without tissue accumulation.

PubMed

Hilty, Florentine M; Arnold, Myrtha; Hilbe, Monika; Teleki, Alexandra; Knijnenburg, Jesper T N; Ehrensperger, Felix; Hurrell, Richard F; Pratsinis, Sotiris E; Langhans, Wolfgang; Zimmermann, Michael B

2010-05-01

Effective iron fortification of foods is difficult, because water-soluble compounds that are well absorbed, such as ferrous sulphate (FeSO(4)), often cause unacceptable changes in the colour or taste of foods. Poorly water-soluble compounds, on the other hand, cause fewer sensory changes, but are not well absorbed. Here, we show that poorly water-soluble nanosized Fe and Fe/Zn compounds (specific surface area approximately 190 m(2) g(-1)) made by scalable flame aerosol technology have in vivo iron bioavailability in rats comparable to FeSO(4) and cause less colour change in reactive food matrices than conventional iron fortificants. The addition of Zn to FePO(4) and Mg to Fe/Zn oxide increases Fe absorption from the compounds, and doping with Mg also improves their colour. After feeding rats with nanostructured iron-containing compounds, no stainable Fe was detected in their gut wall, gut-associated lymphatics or other tissues, suggesting no adverse effects. Nanosizing of poorly water-soluble Fe compounds sharply increases their absorption and nutritional value.

Coniferyl Aldehyde Reduces Radiation Damage Through Increased Protein Stability of Heat Shock Transcriptional Factor 1 by Phosphorylation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Seo-Young; Lee, Hae-June; Nam, Joo-Won

Purpose: We previously screened natural compounds and found that coniferyl aldehyde (CA) was identified as an inducer of HSF1. In this study, we further examined the protective effects of CA against ionizing radiation (IR) in normal cell system. Methods and Materials: Western blotting and reverse transcription-polymerase chain reaction tests were performed to evaluate expression of HSF1, HSP27, and HSP70 in response to CA. Cell death and cleavage of PARP and caspase-3 were analyzed to determine the protective effects of CA in the presence of IR or taxol. The protective effects of CA were also evaluated using animal models. Results: CAmore » increased stability of the HSF1 protein by phosphorylation at Ser326, which was accompanied by increased expression of HSP27 and HSP70. HSF1 phosphorylation at Ser326 by CA was mediated by EKR1/2 activation. Cotreatment of CA with IR or taxol in normal cells induced protective effects with phosphorylation- dependent patterns at Ser326 of HSF1. The decrease in bone marrow (BM) cellularity and increase of terminal deoxynucleotidyl transferase dUTP nick end labeling–positive BM cells by IR were also significantly inhibited by CA in mice (30.6% and 56.0%, respectively). A549 lung orthotopic lung tumor model indicated that CA did not affect the IR-mediated reduction of lung tumor nodules, whereas CA protected normal lung tissues from the therapeutic irradiation. Conclusions: These results suggest that CA may be useful for inducing HSF1 to protect against normal cell damage after IR or chemotherapeutic agents.« less

Authentication of meat products: determination of animal feeding by parallel GC-MS analysis of three adipose tissues.

PubMed

Sivadier, Guilhem; Ratel, Jérémy; Bouvier, Frédéric; Engel, Erwan

2008-11-12

Authentication of farm animal rearing conditions, especially the type of feeding, is a key issue in certification of meat quality and meat products. The purpose of this article was to analyze in parallel the volatile fraction of three adipose tissues excised from 16 lambs in order to authenticate two animal diets: pasture (n = 8) and concentrate (n = 8). On the basis of growth rate and anatomical location, three different lamb adipose tissues were analyzed: perirenal fat (PRF), caudal subcutaneous fat (CSCF), and heart fat (HF). An initial experiment was used to optimize the extraction of volatile compounds from the adipose tissues. Using a lipid liquid phase extraction, heating the ground tissue to 70 degrees C, was shown to be the best sample preparation mode before dynamic headspace-gas chromatography-mass spectrometry (DH-GC-MS) analysis to achieve a good representation of the starting material, while getting a good extraction and reproducibility. Next, the application of an instrumental drifts correction procedure to DH-GC-MS data enabled the identification of 130 volatile compounds that discriminate the two diets in one or several of the three tissues: 104 were found in PRF, 75 in CSCF, and 70 in HF. Forty-eight of these diet tracers, including 2,3-octanedione, toluene, terpenes, alkanes, alkenes, and ketones, had previously been identified as ruminant pasture-diet tracers and can be considered generic of this type of animal feeding. Moreover, 49 of the 130 compounds could identify diets in only one tissue, suggesting that complementary analysis of several tissues is superior for diet identification. Finally, multivariate discriminant analyses confirmed that the discrimination was improved when PRF, CSCF, and HF were considered simultaneously, even if HF contributed minimal information.

Evaluating a switch from meconium to umbilical cord tissue for newborn drug testing: A retrospective study at an academic medical center.

PubMed

Palmer, Kendra L; Wood, Kelly E; Krasowski, Matthew D

2017-04-01

The objective of this study was to compare detection rates of newborn drug exposure at an academic medical center transitioning from meconium to umbilical cord tissue toxicology testing. We performed an Institutional Review Board-approved retrospective chart review on all newborns (n=2072) for whom newborn drug testing was ordered at our academic medical center between June 2012 and August 2015 (in August 2013, umbilical cord tissue became the preferred specimen). Meconium toxicology testing was positive for at least one compound in 221 cases (21.3% of 1037 total specimens), with non-medical drug use identified in 85 cases (8.2%). Umbilical cord tissue toxicology testing was positive for at least one compound in 302 cases (29.2%), with non-medical drug use identified in 107 cases (10.3%). Of the cases involving non-medical drug use, the most common compounds detected were tetrahydrocannabinol and amphetamines. Non-medical drug use did not differ significantly between meconium and umbilical cord tissue, either as a total or for classes of drugs such as amphetamines, cannabinoids, and opiates. Maternal non-medical use of tramadol (not tested for in meconium) was identified in 5 cases (0.4%). There were significant differences in rate of detection of iatrogenic medications. Specifically, morphine, lorazepam, phenobarbital, and codeine were more commonly detected in meconium, while oxycodone was more commonly detected in umbilical cord tissue. Umbilical cord tissue toxicology testing yielded a similar detection rate compared to meconium testing. The use of umbilical cord tissue avoids detection of medications given to the neonate prior to meconium collection. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Biological Activities of Oleanolic Acid Derivatives from Calendula officinalis Seeds.

PubMed

Zaki, Ahmed; Ashour, Ahmed; Mira, Amira; Kishikawa, Asuka; Nakagawa, Toshinori; Zhu, Qinchang; Shimizu, Kuniyoshi

2016-05-01

Phytochemical examination of butanol fraction of Calendula officinalis seeds led to the isolation of two compounds identified as 28-O-β-D-glucopyranosyl-oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS1) and oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS2). Biological evaluation was carried out for these two compounds such as melanin biosynthesis inhibitory, hyaluronic acid production activities, anti obesity using lipase inhibition and adipocyte differentiation as well as evaluation of the protective effect against hydrogen peroxide induced neurotoxicity in neuro-2A cells. The results showed that, compound CS2 has a melanin biosynthesis stimulatory activity; however, compound CS1 has a potent stimulatory effect for the production of hyaluronic acid on normal human dermal fibroblast from adult (NHDF-Ad). Both compounds did not show any inhibitory effect on both lipase and adipocyte differentiation. Compound CS2 could protect neuro-2A cells and increased cell viability against H2 O2 . These activities (melanin biosynthesis stimulatory and protective effect against H2 O2 of CS2 and hyaluronic acid productive activities of these triterpene derivatives) have been reported for the first time. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Parthenolide Selectively Sensitizes Prostate Tumor Tissue to Radiotherapy while Protecting Healthy Tissues In Vivo.

PubMed

Morel, Katherine L; Ormsby, Rebecca J; Bezak, Eva; Sweeney, Christopher J; Sykes, Pamela J

2017-05-01

Radiotherapy is widely used in cancer treatment, however the benefits can be limited by radiation-induced damage to neighboring normal tissues. Parthenolide (PTL) exhibits anti-inflammatory and anti-tumor properties and selectively induces radiosensitivity in prostate cancer cell lines, while protecting primary prostate epithelial cell lines from radiation-induced damage. Low doses of radiation have also been shown to protect from subsequent high-dose-radiation-induced apoptosis as well as DNA damage. These properties of PTL and low-dose radiation could be used to improve radiotherapy by killing more tumor cells and less normal cells. Sixteen-week-old male Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) and C57BL/6J mice were treated with PTL (40 mg/kg), dimethylaminoparthenolide (DMAPT, a PTL analogue with increased bioavailability) (100 mg/kg), or vehicle control three times over one week prior to combinations of low (10 mGy) and high (6 Gy) doses of whole-body X-irradiation. Tissues were analyzed for apoptosis at a range of time points up to 72 h postirradiation. Both PTL and DMAPT protected normal tissues, but not prostate tumor tissues, from a significant proportion of high-dose-radiation-induced apoptosis. DMAPT provided superior protection compared to PTL in normal dorsolateral prostate (71.7% reduction, P = 0.026), spleen (48.2% reduction, P = 0.0001) and colorectal tissue (38.0% reduction, P = 0.0002), and doubled radiation-induced apoptosis in TRAMP prostate tumor tissue (101.3% increase, P = 0.039). Both drugs induced the greatest radiosensitivity in TRAMP prostate tissue in areas with higher grade prostatic intraepithelial neoplasia (PIN) lesions. A 10 mGy dose delivered 3 h prior to a 6 Gy dose induced a radioadaptive apoptosis response in normal C57Bl/6J prostate (28.4% reduction, P = 0.045) and normal TRAMP spleen (13.6% reduction, P = 0.047), however the low-dose-adaptive radioprotection did not significantly add to the PTL/DMAPT-induced protection in normal tissues, nor did it affect tumor kill. These results support the use of the more bioavailable DMAPT and low-dose radiation, alone or in combination as useful radioprotectors of normal tissues to alleviate radiotherapy-induced side-effects in patients. The enhanced radiosensitisation in prostate tissues displaying high-grade PIN suggests that DMAPT also holds promise for targeted therapy of advanced prostate cancer, which may go on to become metastatic. The redox mechanisms involved in the differential radioprotection observed here suggest that increased radiotherapy efficacy by DMAPT is more broadly applicable to a range of cancer types.

PREDICTING THE RISKS OF NEUROTOXIC VOLATILE ORGANIC COMPOUNDS BASED ON TARGET TISSUE DOSE.

EPA Science Inventory

Quantitative exposure-dose-response models relate the external exposure of a substance to the dose in the target tissue, and then relate the target tissue dose to production of adverse outcomes. We developed exposure-dose-response models to describe the affects of acute exposure...

Tylosin depletion in edible tissues of turkeys.

PubMed

Montesissa, C; De Liguoro, M; Santi, A; Capolongo, F; Biancotto, G

1999-10-01

The depletion of tylosin residues in edible turkey tissues was followed after 3 days of administration of tylosin tartrate at 500 mg l-1 in drinking water, to 30 turkeys. Immediately after the end of the treatment (day 0) and at day 1, 3, 5 and 10 of withdrawal, six turkeys (three males and three females) per time were sacrificed and samples of edible tissues were collected. Tissue homogenates were extracted, purified and analysed by HPLC according to a method previously published for the analysis of tylosin residues in pig tissues. In all tissues, tylosin residues were already below the detection limits of 50 micrograms kg-1 at time zero. However, in several samples of tissues (skin + fat, liver, kidney, muscle), from the six turkeys sacrificed at that time, one peak corresponding to an unknown tylosin equivalent was detected at measurable concentrations. The identification of this unknown compound was performed by LC-MS/MS analysis of the extracts from incurred samples. The mass fragmentation of the compound was consistent with the structure of tylosin D (the alcoholic derivative of tylosin A), the major metabolite of tylosin previously recovered and identified in tissues and/or excreta from treated chickens, cattle and pigs.

STUDIES ON THE DISTRIBUTION AND PHOSPHATE TURNOVER OF THE ACID-SOLUBLE PHOSPHORUS COMPOUNDS IN VARIOUS NORMAL AND NEOPLASTIC TISSUES OF RATS. II. COMPARISON OF THE CHROMATOGRAMS OBTAINED WITH VARIOUS TISSUES INCLUDING TUMOURS (ENGLISH TEXT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horie, S.

Using a modified semi-micro gradient elution method of chromatography, the distribution of the acid-soluble nucleotides in various normal and neoplastic tissues of rats was compared and the variations of the distribution are described. The distribution and phosphate turnover of the acid-soluble phosphorus compounds were also studied by intraperitoneal injection of P/sup 32/ followed by the chromatographic analysis. The distribution patterns of nucleotides and radioactivity in liver, muscle, heart, lung, thymus, spleen, testicles, brain, fetal liver, and experimental hepatomas are illustrated and the differences between these tissues were pointed out. The characteristics of the experimental hepatoma tissue as compared with themore » normal liver tissue are as follows: The concentration of oxidized DPN was low; the incorporation of P/sup 32/ inorganic phosphate into glucose 6-phosphate and L- alpha -glycerophosphate was absent or, if any, very low; radioactivity of inorganic phosphate in the total acid-soluble radioactivity was extraordinarily high as compared with other tissues besides the liver tissue. (Abstr. Japan Med., 1: No. 9, 1961)« less

Protective effect of Spirulina platensis enriched in phenolic compounds against hepatotoxicity induced by CCl4.

PubMed

Kepekçi, Remziye Aysun; Polat, Sait; Çelik, Ahmet; Bayat, Nuray; Saygideger, Saadet Demirörs

2013-12-01

Phenolic compounds make up the major secondary metabolites with high pharmaceutical potential. Microalgae were reported to contain low amounts of phenolic compounds. The present study aimed to investigate the hepatoprotective potential of biomass of Spirulina platensis enriched in phenolic compounds. The protective effects of the biomass of S. platensis with low amounts of phenolics (SP1) and with high amounts of phenolics (SP2) against CCl4-induced acute hepatotoxicity were evaluated in rats. The increased levels of ALT, AST and MDA along with decreased activities of SOD and CAT were significantly (p<0.01) ameliorated by SP2. Histological examinations revealed that SP2 was more potent than SP1 in protecting the liver from toxic injury of CCl4 and preserving the hepatocyte ultrastructure. The lesions including necrosis, lymphocyte infiltration, ballooning degeneration and hepatocyte injury as irregular lamellar organisation, dilations in endoplasmic reticulums and the presence of great number of cytoplasmic vacuolization were healed by SP2. Copyright © 2013 Elsevier Ltd. All rights reserved.

Protective effects of levamisole, acetylsalicylic acid, and α-tocopherol against dioxin toxicity measured as the expression of AhR and COX-2 in a chicken embryo model.

PubMed

Gostomska-Pampuch, Kinga; Ostrowska, Alicja; Kuropka, Piotr; Dobrzyński, Maciej; Ziółkowski, Piotr; Kowalczyk, Artur; Łukaszewicz, Ewa; Gamian, Andrzej; Całkosiński, Ireneusz

2017-04-01

Polychlorinated dibenzo-p-dioxins and dibenzofurans (dioxins) are classed as persistent organic pollutants and have adverse effects on multiple functions within the body. Dioxins are known carcinogens, immunotoxins, and teratogens. Dioxins are transformed in vivo, and interactions between the products and the aryl hydrocarbon receptor (AhR) lead to the formation of proinflammatory and toxic metabolites. The aim of this study was to determine whether α-tocopherol (vitamin E), acetylsalicylic acid (ASA), and levamisole can decrease the amount of damage caused by dioxins. Fertile Hubbard Flex commercial line chicken eggs were injected with solutions containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or containing TCDD and the test compounds. The chicken embryos and organs were analyzed after 7 and 13 days. The levels at which AhR and cyclooxygenase-2 (COX-2) proteins (which are induced during inflammation) were expressed were evaluated by performing immunohistochemical analyses on embryos treated with TCDD alone or with TCDD and the test compounds. TCDD caused developmental disorders and increased AhR and COX-2 expression in the chicken embryo tissues. Vitamin E, levamisole, ASA, and ASA plus vitamin E inhibited AhR and COX-2 expression in embryos after 7 days and decreased AhR and COX-2 expression in embryos after 13 days. ASA, levamisole, and ASA plus vitamin E weakened the immune response and prevented multiple organ changes. Vitamin E was not fully protective against developmental changes in the embryos.

Utilization of cytogenetic biomarkers as a tool for assessment of radiation injury and evaluation of radiomodulatory effects of various medicinal plants – a review

PubMed Central

Samarth, Ravindra M; Samarth, Meenakshi; Matsumoto, Yoshihisa

2015-01-01

Systematic biological measurement of “cytogenetic endpoints” has helped phenomenally in assessment of risks associated with radiation exposure. There has been a surge in recent times for the usage of radioactive materials in health care, agriculture, industrial, and nuclear power sectors. The likelihood of radiation exposure from accidental or occupational means is always higher in an overburdened ecosystem that is continuously challenged to meet the population demands. Risks associated with radiation exposure in this era of modern industrial growth are minimal as international regulations for maintaining the safety standards are stringent and strictly adhered to, however, a recent disaster like “Fukushima” impels us to think beyond. The major objective of radiobiology is the development of an orally effective radio-modifier that provides protection from radiation exposure. Once available for mass usage, these compounds will not only be useful for providing selective protection against accidental and occupational radiation exposure but also help to permit use of higher doses of radiation during treatment of various malignancies curtailing unwarranted adverse effects imposed on normal tissues. Bio-active compounds isolated from natural sources enriched with antioxidants possess unique immune-modulating properties, thus providing a double edged benefit over synthetic radioprotectors. We aim to provide here a comprehensive overview of the various agents originating from plant sources that portrayed promising radioprotection in various experimental models with special emphasis on studies that used cytogenetic biomarkers. The agents will include crude extracts of various medicinal plants, purified fractions, and herbal preparations. PMID:26451089

Utilization of cytogenetic biomarkers as a tool for assessment of radiation injury and evaluation of radiomodulatory effects of various medicinal plants - a review.

PubMed

Samarth, Ravindra M; Samarth, Meenakshi; Matsumoto, Yoshihisa

2015-01-01

Systematic biological measurement of "cytogenetic endpoints" has helped phenomenally in assessment of risks associated with radiation exposure. There has been a surge in recent times for the usage of radioactive materials in health care, agriculture, industrial, and nuclear power sectors. The likelihood of radiation exposure from accidental or occupational means is always higher in an overburdened ecosystem that is continuously challenged to meet the population demands. Risks associated with radiation exposure in this era of modern industrial growth are minimal as international regulations for maintaining the safety standards are stringent and strictly adhered to, however, a recent disaster like "Fukushima" impels us to think beyond. The major objective of radiobiology is the development of an orally effective radio-modifier that provides protection from radiation exposure. Once available for mass usage, these compounds will not only be useful for providing selective protection against accidental and occupational radiation exposure but also help to permit use of higher doses of radiation during treatment of various malignancies curtailing unwarranted adverse effects imposed on normal tissues. Bio-active compounds isolated from natural sources enriched with antioxidants possess unique immune-modulating properties, thus providing a double edged benefit over synthetic radioprotectors. We aim to provide here a comprehensive overview of the various agents originating from plant sources that portrayed promising radioprotection in various experimental models with special emphasis on studies that used cytogenetic biomarkers. The agents will include crude extracts of various medicinal plants, purified fractions, and herbal preparations.

Genetic and phenological variation of tocochromanol (vitamin E) content in wild (Daucus carota L. var. carota) and domesticated carrot (D. carota L. var. sativa)

PubMed Central

Luby, Claire H; Maeda, Hiroshi A; Goldman, Irwin L

2014-01-01

Carrot roots (Daucus carota L. var. sativa) produce tocochromanol compounds, collectively known as vitamin E. However, little is known about their types and amounts. Here we determined the range and variation in types and amounts of tocochromanols in a variety of cultivated carrot accessions throughout carrot postharvest storage and reproductive stages and in wild-type roots (Daucus carota L. var. carota). Of eight possible tocochromanol compounds, we detected and quantified α-, and the combined peak for β- and γ- forms of tocopherols and tocotrienols. Significant variation in amounts of tocochromanol compounds was observed across accessions and over time. Large increases in α-tocopherol were noted during both reproductive growth and the postharvest stages. The variation of tocochromanols in carrot root tissue provides useful information for future research seeking to understand the role of these compounds in carrot root tissue or to breed varieties with increased levels of these compounds. PMID:26504534

Synthesis of methylene- and difluoromethylenephosphonate analogues of uridine-4-phosphate and 3-deazauridine-4-phosphate.

PubMed

Taylor, Scott D; Mirzaei, Farzad; Sharifi, Ali; Bearne, Stephen L

2006-12-08

Cytidine triphosphate synthetase (CTPS) catalyzes the formation of cytidine triphosphate from glutamine, uridine-5'-triphosphate (UTP), and adenosine-5'-triphosphate. Inhibitors of CTPS are of interest because of their potential as therapeutic agents. One approach to potent enzyme inhibitors is to use analogues of high energy intermediates formed during the reaction. The CTPS reaction proceeds via the high energy intermediate UTP-4-phosphate (UTP-4-P). Four novel analogues of uridine-4-phosphate (U-4-P) and 3-deazauridine-4-phosphate (3-deazaU-4-P) were synthesized in which the labile phosphate ester oxygen was replaced with a methylene and difluoromethylene group. The methylene analogue of U-4-P, compound 1, was prepared by a reaction of the sodium salt of tert-butyl diethylphosphonoacetate with protected, 4-O-activated uridine followed by acetate deprotection and decarboxylation. It was found that this compound undergoes relatively facile dephosphonylation presumably via a metaphosphate intermediate. The difluoromethylene derivative, compound 2, was prepared by electrophilic fluorination of protected 1. This compound was stable and did not undergo dephosphonylation. Synthesis of the methylene analogue of 3-deazaU-4-P, compound 3, was achieved by ribosylation of protected 4-(phosphonomethyl)-2-hydroxypyridine. Electrophilic fluorination was also employed in the preparation of protected 4-(phosphonodifluoromethyl)-2-hydroxypyridine which was used as the key building block in the synthesis of difluoro derivative 4. These compounds represent the first examples of a nucleoside in which the base has been chemically modified with a methylene or difluormethylenephosphonate group.

DNA damage protection against free radicals of two antioxidant neolignan glucosides from sugarcane molasses.

PubMed

Asikin, Yonathan; Takahashi, Makoto; Mizu, Masami; Takara, Kensaku; Oku, Hirosuke; Wada, Koji

2016-03-15

Sugarcane molasses is a potential by-product of the sugarcane manufacturing industry that is rich in antioxidant materials. The present study aimed to obtain antioxidative compounds from sugarcane molasses and to evaluate their ability to protect DNA from oxidative damage. Two neolignan glucosides were isolated from sugarcane molasses using bioassay and UV spectra monitoring-guided fractionation. The compounds were elucidated as (7R,8S)-dehydrodiconiferyl alcohol-4-O-β-d-glucoside (1) and (7S,8R)-simulanol-9'-O-β-d-glucoside (2). Neolignan glucoside 2 protected against DNA damage caused by free radicals more effectively than did neolignan glucoside 1 (13.62 and 9.08 µmol L(-1) for peroxyl and hydroxyl radicals, respectively, compared to 48.07 and 14.42 µmol L(-1) ). Additionally, neolignan glucoside 2 exhibited superior DNA protection against free radicals compared with various known antioxidative compounds, including p-coumaric acid, ferulic acid, vanillic acid and epigallocatechin gallate. The isolated neolignan glucosides from sugarcane molasses are able to protect DNA from oxidative damage caused by free radicals. This is the first identification of these two compounds in sugarcane molasses. The sugarcane molasses can therefore be used as potential nutraceutical preventative agents, and the findings may foster the utilization of this by-product as a bioresource-based product. © 2015 Society of Chemical Industry. Copyright © 2015 Society of Chemical Industry.

Protecting the Health and Safety of Cell and Tissue Donors.

PubMed

Stroncek, David F; England, Lee

2015-04-01

Centers involved with collecting the starting material for cell and tissue therapies are obligated to protect the recipient's and donor's health and safety. All donors face risks during and after the collection which can be minimized by prescreening donors and excluding those that the collection would place at increased risk of physical harm. Another important part of protecting donors is the use of appropriate collection facilities. Donor risk can also be reduced by using specially designed collection devices and ancillary equipment, using only trained collection staff and limiting the volume or quantity of biologic material collected. Donors should be monitored during and after the collection for adverse events, and should adverse events occur, they should be promptly and appropriately treated. Protecting the safety of cell, gene and tissue donors is particularly difficult because of the wide variety in the types of donors and material collected. Biological material used to manufacture cell and tissue therapies is collected from healthy volunteers, matched-related, matched-unrelated and autologous donors. Precautions should be taken to ensure that the team of medical professionals evaluating related donors is not the same as the team caring for the transplant recipient in order to be sure that the donor evaluation is not biased and the donor is not coerced into donating. In conclusion, protecting cell and tissue donors requires the use of the practices developed to protect blood donors and the implementation of many other measures.

Protecting the Health and Safety of Cell and Tissue Donors

PubMed Central

Stroncek, David F.; England, Lee

2014-01-01

Centers involved with collecting the starting material for cell and tissue therapies are obligated to protect the recipient’s and donor’s health and safety. All donors face risks during and after the collection which can be minimized by prescreening donors and excluding those that the collection would place at increased risk of physical harm. Another important part of protecting donors is the use of appropriate collection facilities. Donor risk can also be reduced by using specially designed collection devices and ancillary equipment, using only trained collection staff and limiting the volume or quantity of biologic material collected. Donors should be monitored during and after the collection for adverse events, and should adverse events occur, they should be promptly and appropriately treated. Protecting the safety of cell, gene and tissue donors is particularly difficult because of the wide variety in the types of donors and material collected. Biological material used to manufacture cell and tissue therapies is collected from healthy volunteers, matched-related, matched-unrelated and autologous donors. Precautions should be taken to ensure that the team of medical professionals evaluating related donors is not the same as the team caring for the transplant recipient in order to be sure that the donor evaluation is not biased and the donor is not coerced into donating. In conclusion, protecting cell and tissue donors requires the use of the practices developed to protect blood donors and the implementation of many other measures. PMID:25937830

40 CFR 721.9970 - o-Xylene compound (generic name).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false o-Xylene compound (generic name). 721... Substances § 721.9970 o-Xylene compound (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as an o-xylene compound (PMN P-95...

Anti-inflammatory effects of polyphenols in arthritis.

PubMed

Oliviero, Francesca; Scanu, Anna; Zamudio-Cuevas, Yessica; Punzi, Leonardo; Spinella, Paolo

2018-03-01

Polyphenols have been extensively investigated with regard to their antioxidant, anti-inflammatory, and immunomodulant properties in many inflammatory chronic conditions. The aim of this review is to summarise how these compounds can modulate the inflammatory pathways which characterise the most prevalent arthropathies including osteoarthritis, rheumatoid arthritis and crystal-induced arthritis. Among polyphenols, epigallocatechin gallate, carnosol, hydroxytyrosol, curcumin, resveratrol, kaempferol and genistein have been the most widely investigated in arthritis. The most important results of the studies outlined in this article show how polyphenolic compounds are able to inhibit the expression and the release of a number of pro-inflammatory mediators and proteolytic enzymes, the activity of different transcriptional factors and the production of reactive oxygen species in vitro. Studies on animal models of rheumatoid arthritis, osteoarthritis and gout show interesting results in terms of reduced tissue damage, restored cartilage homeostasis, and decreased levels of uric acid, respectively. Despite the multiple protective effects of polyphenols, there are no dietary recommendations for patients affected by rheumatic diseases. Future studies, including intervention trials, should be conducted to determine the relevance of polyphenols consumption or supplementation in arthritis. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Development and validation of a physiology-based model for the prediction of pharmacokinetics/toxicokinetics in rabbits

PubMed Central

Hermes, Helen E.; Teutonico, Donato; Preuss, Thomas G.; Schneckener, Sebastian

2018-01-01

The environmental fates of pharmaceuticals and the effects of crop protection products on non-target species are subjects that are undergoing intense review. Since measuring the concentrations and effects of xenobiotics on all affected species under all conceivable scenarios is not feasible, standard laboratory animals such as rabbits are tested, and the observed adverse effects are translated to focal species for environmental risk assessments. In that respect, mathematical modelling is becoming increasingly important for evaluating the consequences of pesticides in untested scenarios. In particular, physiologically based pharmacokinetic/toxicokinetic (PBPK/TK) modelling is a well-established methodology used to predict tissue concentrations based on the absorption, distribution, metabolism and excretion of drugs and toxicants. In the present work, a rabbit PBPK/TK model is developed and evaluated with data available from the literature. The model predictions include scenarios of both intravenous (i.v.) and oral (p.o.) administration of small and large compounds. The presented rabbit PBPK/TK model predicts the pharmacokinetics (Cmax, AUC) of the tested compounds with an average 1.7-fold error. This result indicates a good predictive capacity of the model, which enables its use for risk assessment modelling and simulations. PMID:29561908

Fermented non-digestible fraction from combined nixtamalized corn (Zea mays L.)/cooked common bean (Phaseolus vulgaris L.) chips modulate anti-inflammatory markers on RAW 264.7 macrophages.

PubMed

Luzardo-Ocampo, I; Campos-Vega, R; Cuellar-Nuñez, M L; Vázquez-Landaverde, P A; Mojica, L; Acosta-Gallegos, J A; Loarca-Piña, G

2018-09-01

Chronic non-communicable diseases (NCDs) are low-level inflammation processes affected by several factors including diet. It has been reported that mixed whole grain and legume consumption, e.g. corn and common bean, might be a beneficial combination due to its content of bioactive compounds. A considerable amount would be retained in the non-digestible fraction (NDF), reaching the colon, where microbiota produce short-chain fatty acids (SCFAs) and phenolic compounds (PC) with known anti-inflammatory effect. The aim of this study was to estimate the anti-inflammatory potential of fermented-NDF of corn-bean chips (FNDFC) in RAW 264.7 macrophages. After 24 h, FNDFC produced SCFAs (0.156-0.222 mmol/l), inhibited nitric oxide production > 80% and H 2 O 2  > 30%, up-regulated anti-inflammatory cytokines (I-TAC, TIMP-1) > 2-fold, and produced angiostatic and protective factors against vascular/tissue damage, and amelioration of tumor necrosis factor signalling and inflammatory bowel disease. These results confirm the anti-inflammatory potential derived from healthy corn-bean chips. Copyright © 2018. Published by Elsevier Ltd.

Chinese medicines and bioactive compounds for treatment of stroke.

PubMed

Jayakumar, Thanasekaran; Elizebeth, Antoinet Ramola; Yen, Ting-lin; Sheu, Joen-rong

2015-02-01

Stroke is an important cause of mortality and morbidity worldwide but effective therapeutic strategy for the prevention of brain injury in patients with cerebral ischemia is lacking. Although tissue plasminogen activator has been used to treat stroke patients, this therapeutic strategy is confronted with ill side effects and is limited to patients within 3 h of a stroke. Due to the complexity of the events and the disappointing results from single agent trials, the combination of thrombolytic therapy and effective neural protection therapy may be an alternative strategy for patients with cerebral ischemia. Chinese medicine (CM) is the most widely practiced form of herbalism worldwide, as it is a sophisticated system of medical theory and practice that is specifically different from Western medicine. Most traditional therapeutic formulations consist of a combination of several drugs. The combination of multiple drugs is thought to maximize therapeutic efficacy by facilitating synergistic actions and preventing possible adverse effects while at the same time marking at multiple targets. CM has been labeled in ancient medicine systems as a treatment for various diseases associated with stroke. This review summarizes various CMs, bioactive compounds and their effects on cerebral ischemia.

Injuries to the vascular endothelium: vascular wall and endothelial dysfunction.

PubMed

Fisher, Mark

2008-01-01

Vascular endothelial injury has multiple elements, and this article focuses on ischemia-related processes that have particular relevance to ischemic stroke. Distinctions between necrotic and apoptotic cell death provide a basic science context in which to better understand the significance of classical core and penumbra concepts of acute stroke, with apoptotic processes particularly prominent in the penumbra. The mitochondria are understood to serve as a reservoir of proteins that mediate apoptosis. Oxidative stress pathways generating reactive oxygen species (ROS) are prominent in endothelial injury, both ischemic and nonischemic, with prominent roles of enzyme- and nonenzymemediated pathways; mitochondria once again have a critical role, particularly in the nonenzymatic pathways generating ROS. Inflammation also contributes to vascular endothelial injury, and endothelial cells have the capacity to rapidly increase expression of inflammatory mediators following ischemic challenge; this leads to enhanced leukocyte-endothelial interactions mediated by selectins and adhesion molecules. Preconditioning consists of a minor version of an injurious event, which in turn may protect vascular endothelium from injury following a more substantial event. Presence of the blood-brain barrier creates unique responses to endothelial injury, with permeability changes due to impairment of endothelial-matrix interactions compounding altered vasomotor tone and tissue perfusion mediated by nitric oxide. Pharmacological protection against vascular endothelial injury can be provided by several of the phosphodiesterases (cilostazol and dipyridamole), along with statins. Optimal clinical responses for protection of brain vascular endothelium may use preconditioning as a model, and will likely require combined protection against apoptosis, ROS, and inflammation.

Fermilab Today

Science.gov Websites

certain compound is retained by an animal's tissue, usually the fat tissue. For example, mercury builds up inside salmon fat, and over time, the salmon has a much higher concentration of mercury than does the

The present and future of pharmacotherapy of Alzheimer's disease: A comprehensive review.

PubMed

Anand, Abhinav; Patience, Albert Anosi; Sharma, Neha; Khurana, Navneet

2017-11-15

Alzheimer's disease (AD) is a generalized term used for the loss in memory and other intellectual abilities on levels serious enough to interfere with daily life. It accounts for 60-80% of dementia cases. The characteristic features include aggregation of Amyloid-Beta (Aβ) plaques and Tau Protein Tangles in the nervous tissue of brain. Another important aspect associated with development of AD is the decrease in levels of Acetylcholine (ACh) in brain. The conventional pharmacotherapy of AD employs the use of compounds that inhibit the enzyme acetylcholinesterase (e.g. donepezil, rivastigmine) thereby elevating the levels of Acetylcholine in nervous tissue of brain. Lately, another drug has come into picture for treatment of AD i.e.memantine. It is a Glutamatergic antagonist that protects the nervous tissue against glutamate mediated excitotoxicity. However, both these classes of drugs provide only the symptomatic relief. There has been a desperate need arising since the past few decades for evolution of a drug that could treat the underlying causes of AD and thereby halt its development in susceptible individuals. There are several plants and derived products which have been employed for their benefits against the symptoms and complications of AD. Some novel drugs having the potential to moderate AD are under clinical trials. This review presents a comprehensive overview of the existing and the upcoming potential treatments for AD. Copyright © 2017 Elsevier B.V. All rights reserved.

Lotus japonicus flowers are defended by a cyanogenic β-glucosidase with highly restricted expression to essential reproductive organs.

PubMed

Lai, Daniela; Pičmanová, Martina; Abou Hachem, Maher; Motawia, Mohammed Saddik; Olsen, Carl Erik; Møller, Birger Lindberg; Rook, Fred; Takos, Adam M

2015-09-01

Flowers and leaves of Lotus japonicus contain α-, β-, and γ-hydroxynitrile glucoside (HNG) defense compounds, which are bioactivated by β-glucosidase enzymes (BGDs). The α-HNGs are referred to as cyanogenic glucosides because their hydrolysis upon tissue disruption leads to release of toxic hydrogen cyanide gas, which can deter herbivore feeding. BGD2 and BGD4 are HNG metabolizing BGD enzymes expressed in leaves. Only BGD2 is able to hydrolyse the α-HNGs. Loss of function mutants of BGD2 are acyanogenic in leaves but fully retain cyanogenesis in flowers pointing to the existence of an alternative cyanogenic BGD in flowers. This enzyme, named BGD3, is identified and characterized in this study. Whereas all floral tissues contain α-HNGs, only those tissues in which BGD3 is expressed, the keel and the enclosed reproductive organs, are cyanogenic. Biochemical analysis, active site architecture molecular modelling, and the observation that L. japonicus accessions lacking cyanogenic flowers contain a non-functional BGD3 gene, all support the key role of BGD3 in floral cyanogenesis. The nectar of L. japonicus flowers was also found to contain HNGs and additionally their diglycosides. The observed specialisation in HNG based defence in L. japonicus flowers is discussed in the context of balancing the attraction of pollinators with the protection of reproductive structures against herbivores.

Hepatoprotective effect of chrysin on prooxidant-antioxidant status during ethanol-induced toxicity in female albino rats.

PubMed

Sathiavelu, Jayanthi; Senapathy, Giftson Jebakkan; Devaraj, Rajkumar; Namasivayam, Nalini

2009-06-01

To evaluate the effect of chrysin, a natural, biologically active compound extracted from many plants, honey and propolis, on the tissue and circulatory antioxidant status, and lipid peroxidation in ethanol-induced hepatotoxicity in rats. Rats were divided into four groups. Groups 1 and 2 received isocaloric glucose. Groups 3 and 4 received 20% ethanol, equivalent to 5 g/kg bodyweight every day. Groups 2 and 4 received chrysin (20 mg/kg bodyweight) dissolved in 0.5% dimethylsulfoxide. The results showed significantly elevated levels of tissue and circulatory thiobarbituric acid reactive substances, conjugated dienes and lipid hydroperoxides, and significantly lowered enzymic and non-enzymic antioxidant activity of superoxide dismutase, catalase and glutathione-related enzymes such as glutathione peroxidase, glutathione reductase, glutathione-S-transferase, reduced glutathione, vitamin C and vitamin E in ethanol-treated rats compared with the control. Chrysin administration to rats with ethanol-induced liver injury significantly decreased the levels of thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes, and significantly elevated the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and the levels of reduced glutathione, vitamin C and vitamin E in the tissues and circulation compared with those of the unsupplemented ethanol-treated rats. The histological changes observed in the liver and kidney correlated with the biochemical findings. Chrysin offers protection against free radical-mediated oxidative stress in rats with ethanol-induced liver injury.

High-Throughput Phenotypic Screening of Human Astrocytes to Identify Compounds That Protect Against Oxidative Stress.

PubMed

Thorne, Natasha; Malik, Nasir; Shah, Sonia; Zhao, Jean; Class, Bradley; Aguisanda, Francis; Southall, Noel; Xia, Menghang; McKew, John C; Rao, Mahendra; Zheng, Wei

2016-05-01

Astrocytes are the predominant cell type in the nervous system and play a significant role in maintaining neuronal health and homeostasis. Recently, astrocyte dysfunction has been implicated in the pathogenesis of many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Astrocytes are thus an attractive new target for drug discovery for neurological disorders. Using astrocytes differentiated from human embryonic stem cells, we have developed an assay to identify compounds that protect against oxidative stress, a condition associated with many neurodegenerative diseases. This phenotypic oxidative stress assay has been optimized for high-throughput screening in a 1,536-well plate format. From a screen of approximately 4,100 bioactive tool compounds and approved drugs, we identified a set of 22 that acutely protect human astrocytes from the consequences of hydrogen peroxide-induced oxidative stress. Nine of these compounds were also found to be protective of induced pluripotent stem cell-differentiated astrocytes in a related assay. These compounds are thought to confer protection through hormesis, activating stress-response pathways and preconditioning astrocytes to handle subsequent exposure to hydrogen peroxide. In fact, four of these compounds were found to activate the antioxidant response element/nuclear factor-E2-related factor 2 pathway, a protective pathway induced by toxic insults. Our results demonstrate the relevancy and utility of using astrocytes differentiated from human stem cells as a disease model for drug discovery and development. Astrocytes play a key role in neurological diseases. Drug discovery efforts that target astrocytes can identify novel therapeutics. Human astrocytes are difficult to obtain and thus are challenging to use for high-throughput screening, which requires large numbers of cells. Using human embryonic stem cell-derived astrocytes and an optimized astrocyte differentiation protocol, it was possible to screen approximately 4,100 compounds in titration to identify 22 that are cytoprotective of astrocytes. This study is the largest-scale high-throughput screen conducted using human astrocytes, with a total of 17,536 data points collected in the primary screen. The results demonstrate the relevancy and utility of using astrocytes differentiated from human stem cells as a disease model for drug discovery and development. ©AlphaMed Press.

Protection of Lotus Seedpod Proanthocyanidins on Organs and Tissues under High-intensity Excercise

PubMed Central

Mengyan, Zhang

2015-01-01

Lotus seedpod proanthocyanidins (LSPC) as a kind of polyphenols is widely used in medicines, cosmetics, health products. High-intensity exercise can cause damage to the body's organs and tissues. Different doses of LSPC is given to mice to check the function of protect effect to the body's organs and tissues under high-intensity exercise. The hemoglobin (HB) content, red blood cell (RBC) number and white blood cell (WBC) number were tested for mice after exercise. The activity of superoxide dismutase (SOD) and the contents of glutathione (GSH) and malondialdehyde (MDA) in muscle and viscera were evaluated. The result showed that LSPC can effectively reduce inflammation reaction in the body of mice with high intensity exercise, alleviate oxidative stress-induced injury of tissues and organs, and execute protective function on skeletal muscle and cardiac muscle. And the LSPC could enhance myocardial anti-oxygen and enzymatic activity which suggests the protective effects of resveratrol against exercise-induced myocardial damage in mice. PMID:26998176

Dose effect on the uptake and accumulation of hydroxytyrosol and its metabolites in target tissues in rats.

PubMed

López de las Hazas, Maria-Carmen; Rubió, Laura; Kotronoulas, Aristotelis; de la Torre, Rafael; Solà, Rosa; Motilva, Maria-José

2015-07-01

Hydroxytyrosol (HT) is the most prominent phenolic compound of virgin olive oil and due to its scientifically validated biological activities it is entering to the market as a potentially useful supplement for cardiovascular disease prevention. The aim of the present study was to investigate the relationship between the HT dose intake and its tissue uptake in rats, and thus, providing complementary information in relation to the target-dose relationship. Rats were given a refined olive oil enriched with HT at different doses (1, 10, and 100 mg/kg) and they were sacrificed after 5 h to ensure the cell tissue uptake of HT and its metabolites. Plasma samples and different organs as liver, kidney, heart and brain were obtained, and HT metabolites were analyzed by UPLC-MS/MS. The results showed that HT and its metabolites could be accumulated in a dose-dependent manner basically in the liver, kidney, and brain and were detected in these tissues even at nutritionally relevant human doses. The detection of free HT in liver and kidney was noteworthy. To date, this appears to be the only biologically active form, and thus, it provides relevant information for optimizing the potential applications of HT to prevent certain hepatic and renal diseases. In recent years, HT and its derivatives have led to a great interest from the virgin olive oil producers and manufacturers of nutraceutical supplements. The increasing interest in HT is mainly due to the European Food Safety Agency (EFSA) Panel on Dietetic Products, Nutrition, and Allergies (NDA) scientific opinion that established a cause-and-effect relationship between the consumption of olive oil polyphenols and protection of LDL particles from oxidative damage . Based on this positive opinion, the health claim "Olive oil polyphenols contribute to the protection of blood lipids from oxidative stress" was included in the list of health claims , being the only authorized health claim in the European Union regarding polyphenols and health. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Steroid production and estrogen binding in flowers of Gladiolus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adler, J.H.; Wolfe, G.R.; Janik, J.R.

1987-04-01

The bioconversion of /sup 3/H-cholesterol to steroids was examined in excised tissue from the pistils and bracts of Gladiolus. Ovary-ovule and stigma-style tissues produce a compound with chromatographic properties on reverse phase HPLC similar to 17..beta..-estradiol (E/sub 2/). The stigma-style fraction also produced a compound that chromatographed similarly to progesterone. Bracts and the oxidation controls produced no radiolabeled compounds which were chromatographically similar to E/sub 2/. An endogenous E/sub 2/ binding protein was partially characterized from the ovules. The protein binds E/sub 2/, estriol, and diethylstilbesterol whereas testosterone and progesterone do not bind. The total specific binding capacities in themore » cytosolic and nuclear fractions are 1.6 and 2.2 femtomoles of estradiol per mg of tissue. The dissociation constant is 1.1 x 10/sup -9/ M/sup -1/ for both subcellular fractions. The protein-estradiol complex has a sedimentation coefficient of 4.7 +/- 0.1S. The tissue specific biosynthesis of estrogens and the presence of a steroid binding protein similar to a Type 1 estrogen receptor found in mammals is suggestive of a role for steroids in pistil ontogeny.« less

Uptake, tissue distribution, and metabolism of malachite green in the channel catfish (Ictalurus punctatus)

USGS Publications Warehouse

Plakas, S.M.; El Said, K. R.; Stehly, G.R.; Gingerich, W.H.; Allen, J.L.

1996-01-01

The disposition of malachite green was determined in channel catfish (Ictalurus punctatus) after intravascular dosing (0.8 mg . Kg-1) or waterborne exposure (0.8 mg . L-1 for 1 h). After intravascular dosing, mean plasma concentrations of the parent compound exhibited a triphasic decline with a terminal elimination half-life of 6.2 h. Malachite green was rapidly absorbed and concentrated in the tissues during waterborne exposure. The rate of accumulation was directly related to pH of the exposure water. After waterborne exposure, elimination of the parent compound from plasma also was triphasic with a terminal half-life of 4.7 h. In muscle, the half-life of the parent compound was approximately 67 h. Malachite green and its metabolites were widely distributed in all tissues. In fish exposed to C-14-labeled malachite green, total drug equivalent concentrations were highest in abdominal fat and lowest in plasma. Malachite green was rapidly and extensively metabolized to its reduced form, leucomalachite green, which was slowly eliminated from the tissues. Leucomalachite green is an appropriate target analyte for monitoring exposure of channel catfish to this drug.

Poisoning of wild birds from exposure to anticholinesterase compounds and lead: diagnostic methods and selected cases

USGS Publications Warehouse

Franson, J. Christian; Smith, Milton R.

1999-01-01

Organophosphorus and carbamate compounds have largely replaced chlorinated hydrocarbons for pesticidal use in the United States, and many cases of poisoning resulting from exposure to these anticholinesterase agents have occurred in free-living birds. Although lead shot has been prohibited for waterfowl hunting throughout the United States since 1991, lead poisoning from the ingestion of spent lead shot is still occasionally seen in wild birds, and lead poisoning from the ingestion of fishing sinkers is an emerging issue of concern. A thorough history, a complete necropsy evaluation, and appropriate laboratory analysis of tissues are required to diagnose toxicoses in wild birds, including those caused by anticholinesterase compounds and lead. The interpretation of brain cholinesterase (ChE) activity results depends on the methods of analysis and comparison with expected normal enzyme activities in brain tissue from the same species. Although lead residues in tissues vary among species, many lead poisoned birds have tissue residues that are much higher than the lower threshold commonly accepted for a diagnosis of lead poisoning. We review histories, necropsy findings, and analytical methodologies and results for selected anticholinesterase and lead poisoning cases diagnosed in wild raptors, waterfowl, and loons.

Contaminants of emerging concern in a large temperate estuary.

PubMed

Meador, James P; Yeh, Andrew; Young, Graham; Gallagher, Evan P

2016-06-01

This study was designed to assess the occurrence and concentrations of a broad range of contaminants of emerging concern (CECs) from three local estuaries within a large estuarine ecosystem. In addition to effluent from two wastewater treatment plants (WWTP), we sampled water and whole-body juvenile Chinook salmon (Oncorhynchus tshawytscha) and Pacific staghorn sculpin (Leptocottus armatus) in estuaries receiving effluent. We analyzed these matrices for 150 compounds, which included pharmaceuticals, personal care products (PPCPs), and several industrial compounds. Collectively, we detected 81 analytes in effluent, 25 analytes in estuary water, and 42 analytes in fish tissue. A number of compounds, including sertraline, triclosan, estrone, fluoxetine, metformin, and nonylphenol were detected in water and tissue at concentrations that may cause adverse effects in fish. Interestingly, 29 CEC analytes were detected in effluent and fish tissue, but not in estuarine waters, indicating a high potential for bioaccumulation for these compounds. Although concentrations of most detected analytes were present at relatively low concentrations, our analysis revealed that overall CEC inputs to each estuary amount to several kilograms of these compounds per day. This study is unique because we report on CEC concentrations in estuarine waters and whole-body fish, which are both uncommon in the literature. A noteworthy finding was the preferential bioaccumulation of CECs in free-ranging juvenile Chinook salmon relative to staghorn sculpin, a benthic species with relatively high site fidelity. Published by Elsevier Ltd.

Preventive Effect of Dihydromyricetin against Cisplatin-Induced Nephrotoxicity In Vitro and In Vivo

PubMed Central

2016-01-01

Nephrotoxicity is a frequent severe side effect of cisplatin chemotherapy, limiting its clinical use despite being one of the most potent chemotherapy drugs. Dihydromyricetin is a highly abundant compound purified from the leaves of Ampelopsis grossedentata. Previous studies have demonstrated the anti-inflammatory and antioxidative effects of Dihydromyricetin both in vitro and in vivo, but little is known about the effects of Dihydromyricetin on cisplatin-induced nephrotoxicity and its underlying mechanisms. In the present study, we investigated its potential renoprotective effect and found that Dihydromyricetin ameliorated the renal functional impairment and structural damage caused by cisplatin. Moreover, Dihydromyricetin markedly attenuated cisplatin-induced oxidative stress, as well as protecting against cisplatin-induced inflammation and apoptotic cell death in mouse kidney tissues. These results collectively highlight the potential of DMY as a rational renoprotective agent against cisplatin. PMID:27642358

A novel vaccine targeting Fusobacterium nucleatum against abscesses and halitosis

PubMed Central

Liu, Pei-Feng; Haake, Susan Kinder; Gallo, Richard L.; Huang, Chun-Ming

2011-01-01

An abscess in a gum pocket, resulting from bacterial infection, is a common source of chronic halitosis. Although antibiotics are generally prescribed for abscesses, they require multiple treatments with risks of creating resistant bacterial strains. Here we develop a novel vaccine using ultraviolet-inactivated Fusobacterium nucleatum (F. nucleatum), a representative oral bacterium for halitosis. A gum pocket model, established by continuous inoculation of F. nucleatum, was employed to validate the vaccine potency. Mice immunized with inactivated F. nucleatum effectively minimized the progression of abscesses, measured by swollen tissues of gum pockets. Most notably, the immunized mice were capable of eliciting neutralizing antibodies against the production of volatile sulfur compounds of F. nucleatum. The novel vaccine inducing protective immunity provides an alternative option to conventional antibiotic treatments for chronic halitosis associated with abscesses. PMID:19162109

[Free radicals of oxygen and superoxide dismutase. Biological and medical aspects].

PubMed

Monte, M; Sacerdote de Lustig, E

1994-01-01

Oxygen free radicals (OFR) are very reactive and unstable metabolites capable of altering important biomolecules including proteins, lipids and nucleic acids. OFR are regulated by enzymes such as superoxide dismutases (SOD), catalase, glutation peroxidase and by molecules such as vitamins E, A, C, and K, selenio, cystein and other compounds. Increased OFR levels due to an overproduction of these metabolites or to a failure in the control system, induce cellular and tissue injuries that could lead to diseases such as atherosclerosis, arthritis, fibrosis, lung and heart injuries, neurological disorders and cancer. In this article we consider the use of SOD as therapeutic agents both in human and experimental models. We also refer to the administration of SOD as a protective factor against secondary injuries during radiotherapy and to the determination of SOD as a tumor marker.

Discovering erythropoietin's extra-hematopoietic functions: biology and clinical promise.

PubMed

Brines, M; Cerami, A

2006-07-01

A greatly expanded understanding of the biology of endogenous erythropoietin (EPO) has emerged since the early 1990s. Originally viewed as the renal hormone dedicated to erythrocyte production, it is now clear that EPO is produced locally by many other tissues in response to physical or metabolic stress. In its autocrine-paracrine roles, EPO mediates preconditioning (ischemic tolerance) and specifically limits the destructive potential of tumor necrosis factor alpha and other proinflammatory cytokines in the brain, heart, kidney, and other tissues. As local production of EPO is generally suppressed following injury, administration of exogenous EPO has been a successful therapeutic approach in preclinical and clinical studies, for example, following ischemia-reperfusion and toxin-induced renal injuries, and in human stroke. The therapeutic time window of tissue protection by EPO is typically very wide in experimental models, showing effectiveness when administered before, during, or after an insult and raising optimism for a high clinical potential. Although there is progress in understanding the signaling pathways responsible for EPO's tissue-protective actions that are similar to, but not as redundant as, those employed for erythrocyte maturation, much work remains to be carried out. Experimental observations also suggest the existence of EPO receptor (EPOR) isoforms mediating EPO's diverse biological activities and have identified a tissue-protective receptor complex consisting of the EPOR and the beta common receptor (CD131) subunit that is also employed by granulocyte-macrophage colony-stimulating factor, interleukin-3 and interleukin-5. Successfully engineered analogues of EPO that selectively activate tissue protection without stimulating hematopoiesis confirm the concept of a tissue-protective receptor and have significant potential utility in the investigational and therapeutic arenas.

Montmorillonite Functionalized with Pralidoxime as a Material for Chemical Protection against Organophosphorous Compounds

DTIC Science & Technology

2011-03-25

implied is via iondipole forces.5,6 It is well-known that clays such as montmorillonite and kaolinite accelerate the degradation of insecticides such...REPORT Montmorillonite Functionalized with Pralidoxime As a Material for Chemical Protection against Organophosphorous Compounds 14. ABSTRACT 16...SECURITY CLASSIFICATION OF: Montmorillonite K-10 functionalized with ?-nucleophilic 2-pralidoxime (PAM) and its zwitterionic oximate form (PAMNa) is

Repellency and Larvicidal Activity of Essential oils from Xylopia laevigata, Xylopia frutescens, Lippia pedunculosa, and Their Individual Compounds against Aedes aegypti Linnaeus.

PubMed

Nascimento, A M D; Maia, T D S; Soares, T E S; Menezes, L R A; Scher, R; Costa, E V; Cavalcanti, S C H; La Corte, R

2017-04-01

In order to find new alternatives for vector control and personal protection, we evaluated the larvicidal and repellent activity of essentials oils from plants found in the Northeast of Brazil against Aedes aegypti Linnaeus mosquitoes. The plants tested include Xylopia laevigata, Xylopia frutescens, and Lippia pedunculosa and their major compounds, piperitenone oxide, and (R)-limonene. The essential oil of L. pedunculosa and its major volatile compounds were shown to be toxic for Ae. aegypti larvae with a LC 50 lower than 60 ppm. The essential oil of plants from the Xylopia genus, on the other hand, showed no activity against Ae. aegypti, proving to be toxic to mosquito larvae only when concentrations were higher than 1000 ppm. All plants tested provided some degree of protection against mosquitoes landing, but only the essential oil of L. pedunculosa and the volatile compound piperitenone oxide suppressed 100% of mosquitoes landing on human skin, in concentrations lower than 1%. Among the plants studied, the essential oil of L. pedunculosa and its volatiles compounds have shown the potential for the development of safe alternative for mosquito larvae control and protection against Ae. aegypti mosquito bites.

Biomimetic three-dimensional tissue models for advanced high-throughput drug screening

PubMed Central

Nam, Ki-Hwan; Smith, Alec S.T.; Lone, Saifullah; Kwon, Sunghoon; Kim, Deok-Ho

2015-01-01

Most current drug screening assays used to identify new drug candidates are 2D cell-based systems, even though such in vitro assays do not adequately recreate the in vivo complexity of 3D tissues. Inadequate representation of the human tissue environment during a preclinical test can result in inaccurate predictions of compound effects on overall tissue functionality. Screening for compound efficacy by focusing on a single pathway or protein target, coupled with difficulties in maintaining long-term 2D monolayers, can serve to exacerbate these issues when utilizing such simplistic model systems for physiological drug screening applications. Numerous studies have shown that cell responses to drugs in 3D culture are improved from those in 2D, with respect to modeling in vivo tissue functionality, which highlights the advantages of using 3D-based models for preclinical drug screens. In this review, we discuss the development of microengineered 3D tissue models which accurately mimic the physiological properties of native tissue samples, and highlight the advantages of using such 3D micro-tissue models over conventional cell-based assays for future drug screening applications. We also discuss biomimetic 3D environments, based-on engineered tissues as potential preclinical models for the development of more predictive drug screening assays for specific disease models. PMID:25385716

[Protective effect and mechanism of compound Ginkgo biloba granules on oxidative stress injury of HUVEC].

PubMed

Li, Qi; Chen, Xi; Kan, Xiao-Xi; Li, Yu-Jie; Yang, Qing; Wang, Ya-Jie; Chen, Ying; Weng, Xiao-Gang; Cai, Wei-Yan; Huang, He-Fei; Zhu, Xiao-Xin

2016-02-01

To reveal the protective and anti-apoptosis effect of compound Ginkgo biloba granules on oxidative stress injury of human umbilical vein endothelial cells (HUVEC). Negative control group, H2O2 model group and 4 drug pretreatment groups (80, 160, 320, 640 mg• L⁻¹) were established. The cell proliferation, morphological changes in each group after oxidative stress injury was detected by MTT assay and through microscope observation respectively. The content of LDH, MDA, SOD and NO and SOD activity in supernatant were detected to judge the protection effect of the drugs on endothelial cells. The protective effect on HUVEC apoptosis was analyzed by Caspase-3 activity test and Annexin V-FITC/PI staining. Western blot was used to observe the expression of apoptosis-related proteins Bcl-2 and Bax. Results showed that 1 200 μmol• L⁻¹ H2O2 can induce oxidative stress injury in endothelial cells and reduce the cell survival rate; cell proliferation inhibition degree is positively correlated with the effect time of H2O2. Besides, 80, 160, 320 640 mg•L⁻¹ compound Ginkgo biloba granules can protect HUVEC from oxidative stress injury, recover the normal proliferation level of cells, improve their state, prohibit cell apoptosis, and can up-regulate and down-regulate the expression level of Bcl-2 and Bax respectively. In conclusion, compound G. biloba granules can protect HUVEC from the oxidative stress injury induced by H2O2, its mechanism may be correlated with inhibition of the mitochondrial apoptotic pathway in HUVEC. Copyright© by the Chinese Pharmaceutical Association.

Host protective roles of type 2 immunity: Parasite killing and tissue repair, flip sides of the same coin

PubMed Central

Allen, Judith E.; Sutherland, Tara E.

2014-01-01

Metazoan parasites typically induce a type 2 immune response, characterized by T helper 2 (Th2) cells that produce the cytokines IL-4, IL-5 and IL-13 among others. The type 2 response is host protective, reducing the number of parasites either through direct killing in the tissues, or expulsion from the intestine. Type 2 immunity also protects the host against damage mediated by these large extracellular parasites as they migrate through the body. At the center of both the innate and adaptive type 2 immune response, is the IL-4Rα that mediates many of the key effector functions. Here we highlight the striking overlap between the molecules, cells and pathways that mediate both parasite control and tissue repair. We have proposed that adaptive Th2 immunity evolved out of our innate repair pathways to mediate both accelerated repair and parasite control in the face of continual assault from multicellular pathogens. Type 2 cytokines are involved in many aspects of mammalian physiology independent of helminth infection. Therefore understanding the evolutionary relationship between helminth killing and tissue repair should provide new insight into immune mechanisms of tissue protection in the face of physical injury. PMID:25028340

Extra-Virgin Olive Oil with Natural Phenolic Content Exerts an Anti-Inflammatory Effect in Adipose Tissue and Attenuates the Severity of Atherosclerotic Lesions in Ldlr-/-.Leiden Mice.

PubMed

Luque-Sierra, Amparo; Alvarez-Amor, Leticia; Kleemann, Robert; Martín, Franz; Varela, Lourdes M

2018-05-15

The present study investigates the effect of olive oils with different phenolic content in high-fat diets (HFDs) on hypertrophy and inflammation in adipose tissue and associated atherosclerosis, in the context of obesity. Ldlr-/-.Leiden mice were fed three different HFDs for 32 weeks and were compared with mice fed the standard low-fat diet (LFD). The different fats provided in the HFDs were lard (HFD-L), extra-virgin olive oil (EVOO; 79 mg kg -1 of phenolic compounds, HFD-EVOO), or EVOO rich in phenolic compounds (OL, 444 mg kg -1 of phenolic compounds, HFD-OL). All HFD-fed mice became obese, but only HFD-L-induced adipocyte hypertrophy. HFD-EVOO mice exhibited the greatest levels of Adiponectin in adipose tissue and presented atherosclerotic lesions similar to the LFD group, with a very low count of monocyte/macrophage compared with HFD-L and HFD-OL mice. Enrichment of the phenolic content of olive oil reduced the secretion of nitrites/nitrates in the aorta, but atherosclerosis was not attenuated in HFD-OL mice compared to other HFD mice. Consumption of olive oil with a natural content of phenolic compounds attenuates adipose tissue hypertrophy and inflammation and exerts antiatherosclerotic effects in mice. A higher phenolic content of olive oil did not provide further benefits in the prevention of atherosclerosis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phenolic metabolites in plasma and tissues of rats fed with a grape pomace extract as assessed by liquid chromatography-tandem mass spectrometry.

PubMed

Rodriguez Lanzi, Cecilia; Perdicaro, Diahann J; Antoniolli, Andrea; Piccoli, Patricia; Vazquez Prieto, Marcela A; Fontana, Ariel

2018-05-31

Grape pomace extract (GPE) is a rich and relatively low-cost source of phenolic compounds. However, little is known about the main GPE metabolites in mammals, which could help explain the observed health-promoting effects. This study investigated the presence of parent compounds from flavanol, flavonol and stilbene families and their metabolites in rat plasma and tissues after an acute intake of GPE in doses of 300 and 600 mg kg/body weight. The measurement of free compounds and their metabolites was performed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Results showed the presence of epicatechin, epicatechin methyl-glucuronide, epicatechin methyl-sulphate, catechin, catechin-glucuronide, quercetin methyl-glucuronide, resveratrol-3-glucuronide, resveratrol-4-glucuronide and resveratrol-3-sulphate in plasma, which was dose dependent. The most abundant measured compound in plasma was epicatechin-glucuronide. The presence of glucuronidated and methyl-glucuronidated forms of catechin were observed in the liver at both doses, while epicatechin-glucuronide and methyl-glucuronide were detected only upon intake of 600 mg GPE/kg body weight. At this dose epicatechin-glucuronide and methyl-glucuronide were also detected in muscle, and catechin methyl-glucuronide in adipose tissue. Results show the main GPE metabolites present in rat tissues after oral consumption, contributing to better understand the health benefits of GPE and its potential utilization as a functional ingredient. Copyright © 2018. Published by Elsevier Inc.

Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best?

PubMed

Uysal, Nazan; Kizildag, Servet; Yuce, Zeynep; Guvendi, Guven; Kandis, Sevim; Koc, Basar; Karakilic, Aslı; Camsari, Ulas M; Ates, Mehmet

2018-04-21

Magnesium is an element of great importance functioning because of its association with many cellular physiological functions. The magnesium content of foods is gradually decreasing due to food processing, and magnesium supplementation for healthy living has become increasingly popular. However, data is very limited on the bioavailability of various magnesium preparations. The aim of this study is to investigate the bioavailability of five different magnesium compounds (magnesium sulfate, magnesium oxide, magnesium acetyl taurate, magnesium citrate, and magnesium malate) in different tissues. Following a single dose 400 mg/70 kg magnesium administration to Sprague Dawley rats, bioavailability was evaluated by examining time-dependent absorption, tissue penetration, and the effects on the behavior of the animals. Pharmacokinetically, the area under the curve calculation is highest in the magnesium malate. The magnesium acetyl taurate was found to have the second highest area under the curve calculation. Magnesium acetyl taurate was rapidly absorbed, able to pass through to the brain easily, had the highest tissue concentration level in the brain, and was found to be associated with decreased anxiety indicators. Magnesium malate levels remained high for an extended period of time in the serum. The commonly prescribed dietary supplements magnesium oxide and magnesium citrate had the lowest bioavailability when compared to our control group. More research is needed to investigate the bioavailability of magnesium malate and acetyl taurate compounds and their effects in specific tissues and on behavior.

Spectromicroscopy of boron in human glioblastomas following administration of Na2B12H11SH.

PubMed

Gilbert, B; Perfetti, L; Fauchoux, O; Redondo, J; Baudat, P A; Andres, R; Neumann, M; Steen, S; Gabel, D; Mercanti, D; Ciotti, M T; Perfetti, P; Margaritondo, G; De Stasio, G

2000-07-01

Boron neutron capture therapy (BNCT) is an experimental, binary treatment for brain cancer which requires as the first step that tumor tissue is targeted with a boron-10 containing compound. Subsequent exposure to a thermal neutron flux results in destructive, short range nuclear reaction within 10 microm of the boron compound. The success of the therapy requires than the BNCT agents be well localized in tumor, rather than healthy tissue. The MEPHISTO spectromicroscope, which performs microchemical analysis by x-ray absorption near edge structure (XANES) spectroscopy from microscopic areas, has been used to study the distribution of trace quantities of boron in human brain cancer tissues surgically removed from patients first administered with the compound Na2B12H11SH (BSH). The interpretation of XANES spectra is complicated by interference from physiologically present sulfur and phosphorus, which contribute structure in the same energy range as boron. We addressed this problem with the present extensive set of spectra from S, B, and P in relevant compounds. We demonstrate that a linear combination of sulfate, phosphate and BSH XANES can be used to reproduce the spectra acquired on boron-treated human brain tumor tissues. We analyzed human glioblastoma tissue from two patients administered and one not administered with BSH. As well as weak signals attributed to BSH, x-ray absorption spectra acquired from tissue samples detected boron in a reduced chemical state with respect to boron in BSH. This chemical state was characterized by a sharp absorption peak at 188.3 eV. Complementary studies on BSH reference samples were not able to reproduce this chemical state of boron, indicating that it is not an artifact produced during sample preparation or x-ray exposure. These data demonstrate that the chemical state of BSH may be altered by in vivo metabolism.

Sansevieria roxburghiana Schult. & Schult. F. (Family: Asparagaceae) Attenuates Type 2 Diabetes and Its Associated Cardiomyopathy.

PubMed

Bhattacharjee, Niloy; Khanra, Ritu; Dua, Tarun K; Das, Susmita; De, Bratati; Zia-Ul-Haq, M; De Feo, Vincenzo; Dewanjee, Saikat

2016-01-01

Sansevieria roxburghiana Schult. & Schult. F. (Family: Asparagaceae) rhizome has been claimed to possess antidiabetic activity in the ethno-medicinal literature in India. Therefore, present experiments were carried out to explore the protective role of edible (aqueous) extract of S. roxburghiana rhizome (SR) against experimentally induced type 2 diabetes mellitus (T2DM) and its associated cardiomyopathy in Wistar rats. SR was chemically characterized by GC-MS analysis. Antidiabetic activity of SR (50 and 100 mg/kg, orally) was measured in high fat diets (ad libitum) + low-single dose of streptozotocin (35 mg/kg, intraperitoneal) induced type 2 diabetic (T2D) rat. Fasting blood glucose level was measured at specific intermissions. Serum biochemical and inflammatory markers were estimated after sacrificing the animals. Besides, myocardial redox status, expressions of signal proteins (NF-κB and PKCs), histological and ultrastructural studies of heart were performed in the controls and SR treated T2D rats. Phytochemical screening of the crude extract revealed the presence of phenolic compounds, sugar alcohols, sterols, amino acids, saturated fatty acids within SR. T2D rats exhibited significantly (p < 0.01) higher fasting blood glucose level with respect to control. Alteration in serum lipid profile (p < 0.01) and increased levels of lactate dehydrogenase (p < 0.01) and creatine kinase (p < 0.01) in the sera revealed the occurrence of hyperlipidemia and cell destruction in T2D rats. T2DM caused significant (p < 0.05-0.01) alteration in the biochemical markers in the sera. T2DM altered the redox status (p < 0.05-0.01), decreased (p < 0.01) the intracellular NAD and ATP concentrations in the myocardial tissues of experimental rats. While investigating the molecular mechanism, activation PKC isoforms was observed in the selected tissues. T2D rats also exhibited an up-regulation in nuclear NF-κB (p65) in the cardiac tissues. So, oral administration of SR (50 and 500 mg/kg) could reduce hyperglycemia, hyperlipidemia, membrane disintegration, oxidative stress, vascular inflammation and prevented the activation of oxidative stress induced signaling cascades leading to cell death. Histological and ultra-structural studies of cardiac tissues supported the protective characteristics of SR. From the present findings it can be concluded that, SR could offer protection against T2DM and its associated cardio-toxicity via multiple mechanisms viz. hypoglycemic, antioxidant and anti-inflammatory actions.

40 CFR 721.5330 - Nickel salt of an organo compound containing nitrogen.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Nickel salt of an organo compound... Specific Chemical Substances § 721.5330 Nickel salt of an organo compound containing nitrogen. (a) Chemical... as nickel salt of an organo compound containing nitrogen (PMN P-92-686) is subject to reporting under...

40 CFR 721.5330 - Nickel salt of an organo compound containing nitrogen.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Nickel salt of an organo compound... Specific Chemical Substances § 721.5330 Nickel salt of an organo compound containing nitrogen. (a) Chemical... as nickel salt of an organo compound containing nitrogen (PMN P-92-686) is subject to reporting under...

40 CFR 721.5330 - Nickel salt of an organo compound containing nitrogen.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Nickel salt of an organo compound... Specific Chemical Substances § 721.5330 Nickel salt of an organo compound containing nitrogen. (a) Chemical... as nickel salt of an organo compound containing nitrogen (PMN P-92-686) is subject to reporting under...

40 CFR 721.5330 - Nickel salt of an organo compound containing nitrogen.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Nickel salt of an organo compound... Specific Chemical Substances § 721.5330 Nickel salt of an organo compound containing nitrogen. (a) Chemical... as nickel salt of an organo compound containing nitrogen (PMN P-92-686) is subject to reporting under...

40 CFR 721.5330 - Nickel salt of an organo compound containing nitrogen.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Nickel salt of an organo compound... Specific Chemical Substances § 721.5330 Nickel salt of an organo compound containing nitrogen. (a) Chemical... as nickel salt of an organo compound containing nitrogen (PMN P-92-686) is subject to reporting under...

Distribution of ibogaine and noribogaine in a man following a poisoning involving root bark of the Tabernanthe iboga shrub.

PubMed

Kontrimaviciūte, Violeta; Mathieu, Olivier; Mathieu-Daudé, Jean-Claude; Vainauskas, Paulius; Casper, Thierry; Baccino, Eric; Bressolle, Françoise M M

2006-09-01

In the present paper, we report for the first time the tissue distribution of ibogaine and noribogaine, the main metabolite of ibogaine, in a 48-year-old Caucasian male, with a history of drug abuse, found dead at his home after a poisoning involving the ingestion of root bark from the shrub Tabernanthe iboga. Ibogaine and noribogaine were quantified in tissues and fluids using a fully validated liquid chromatography-electrospray mass spectrometry method. Apart from cardiac tissue, ibogaine and noribogaine were identified in all matrices investigated. The highest concentrations were found in spleen, liver, brain, and lung. The tissue/subclavian blood concentration ratios averaged 1.78, 3.75, 1.16, and 4.64 for ibogaine and 0.83, 2.43, 0.90, and 2.69 for noribogaine for spleen, liver, brain, and lung, respectively. Very low concentrations of the two drugs were found in the prostatic tissue. Both ibogaine and noribogaine are secreted in the bile and cross the blood-brain barrier. Four other compounds were detected in most of the studied matrices. One of them was identified as ibogamine. Unfortunately, we were not able to positively identify the other three compounds because of the unavailability of reference substances. Two of them could possibly be attributed to the following oxidation products: iboluteine and desmethoxyiboluteine. The third compound could be ibogaline.

Down-regulation of the detoxifying enzyme NAD(P)H:quinone oxidoreductase 1 by vanadium in Hepa 1c1c7 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anwar-Mohamed, Anwar; El-Kadi, Ayman O.S.

2009-05-01

Recent data suggest that vanadium (V{sup 5+}) compounds exert protective effects against chemical-induced carcinogenesis, mainly through modifying various xenobiotic metabolizing enzymes. In fact, we have shown that V{sup 5+} down-regulates the expression of Cyp1a1 at the transcriptional level through an ATP-dependent mechanism. However, incongruously, there is increasing evidence that V{sup 5+} is found in higher amounts in cancer cells and tissues than in normal cells or tissues. Therefore, the current study aims to address the possible effect of this metal on the regulation of expression of an enzyme that helps maintain endogenous antioxidants used to protect tissues/cells from mutagens, carcinogens,more » and oxidative stress damage, NAD(P)H:quinone oxidoreductase 1 (Nqo1). In an attempt to examine these effects, Hepa 1c1c7 cells and its AhR-deficient version, c12, were treated with increasing concentrations of V{sup 5+} in the presence of two distinct Nqo1 inducers, the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and isothiocyanate sulforaphane (SUL). Our results showed that V{sup 5+} inhibits the TCDD- and SUL-mediated induction of Nqo1 at mRNA, protein, and catalytic activity levels. At transcriptional level, V{sup 5+} was able to decrease the TCDD- and SUL-induced nuclear accumulation of Nrf2 and the subsequent binding to antioxidant responsive element (ARE) without affecting Nrf2 protein levels. Looking at post-transcriptional level; we found that V{sup 5+} did not affect Nqo1 mRNA transcripts turn-over rates. However, at the post-translational level V{sup 5+} increased Nqo1 protein half-life. In conclusion, the present study demonstrates that V{sup 5+} down-regulates Nqo1 at the transcriptional level, possibly through inhibiting the ATP-dependent activation of Nrf2.« less

Protective effects of fennel oil extract against sodium valproate-induced hepatorenal damage in albino rats.

PubMed

Al-Amoudi, Wael M

2017-05-01

Foeniculum vulgare (Apiaceae) is commonly known as fennel. This herb is well-known worldwide and traditionally used as curative herbal therapy for the treatment of epileptic disease, seizurescarminative, digestive, lactogogue, diuretic, treating respiratory and gastrointestinal disorders. The aim of present study is to investigate the possible effect of fennel oil against the toxicity of Sodium-Valproic (SVP) in albino rats. In order to assess the protection of fennel oil on SVP induced hepato- and nephro-toxicity, male albino rats were treated with 1 ml/kg b.w fennel oil 3 days/week for 6 weeks. The biochemical analyses of hepatic enzymes were evaluated by estimating blood biomarkers of liver and renal damage along with histological examination. The results obtained from this work showed that treating animals with SVP lead to many histopathological alterations in the liver and kidney tissues. The effect appeared in the liver tissue include leukocyte infiltrations, cytoplasmic vacuolization of the hepatocytes, fatty degeneration and congestion of blood vessels. This commonly used chemical (SVP) caused some unwanted effects on the kidney cortex which histologically observed as degeneration in renal tubules, atrophy of the glomeruli and edema. Biochemical results also revealed an abnormal increase in the enzyme level of AST, SAT, ALP, bilirubin, creatinine and urea-nitrogen, with a noticed decrease in total protein content. However, the results of treated rats with SVP plus fennel oil showed some positive histopathological changes in both the liver and kidney tissues. These results have confirmed that fennel oil has positive effects on the histological structure of the liver and kidney and the biochemical levels of AST, ALT, ALP, bilirubin, total proteins, creatinine and urea. It is concluded that fennel oil has various pharmacological properties including antioxidant, anti-cancer activity, anti-inflammatory. These valuable effects might be due to the presence of aromatic compounds trans -anethole. This useful properties of fennel plant could be due to its antioxidant activity that prevents the toxicity of SVP.

Hydroalcoholic extract of Brazilian red propolis exerts protective effects on acetic acid-induced ulcerative colitis in a rodent model.

PubMed

Barbosa Bezerra, Gislaine; de Menezes de Souza, Luana; Dos Santos, Adailma Santana; de Almeida, Grace Kelly Melo; Souza, Marília Trindade Santana; Santos, Sandra Lauton; Aparecido Camargo, Enilton; Dos Santos Lima, Bruno; de Souza Araújo, Adriano Antunes; Cardoso, Juliana Cordeiro; Gomes, Silvana Vieira Floresta; Gomes, Margarete Zanardo; de Albuquerque, Ricardo Luiz Cavalcanti

2017-01-01

Ulcerative colitis (UC) is a common intestinal inflammatory disease with an etiology that is not well understood. Although the anti-inflammatory and anti-oxidant effects of the hydroalcoholic extract of Brazilian red propolis (HERP) have been reported in various experimental models, its protective effect in models of UC have not been evaluated. The purpose of this study was to investigate the chemopreventive effect of hydroalcoholic extract of Brazilian red propolis (HERP) in acetic acid-induced colitis (AAIC) using a rodent model. The HERP was chemically characterised by HPLC/DAD analyses. Male rats were randomly assigned into four groups: sham, vehicle (with AAIC, treated with vehicle), P10 (with AAIC, treated with 10mg/kg HERP), and P100 (with AAIC, treated with 100mg/kg HERP). Treatments were performed for 7days, and colitis was induced on day seven. Animals were euthanized 24h after colitis induction and body weight, colon length, gross and histological scores, malondialdehyde (MDA) and myeloperoxidase (MPO) concentrations in colon tissue, and the immunohistochemical expression of inducible nitric oxide synthase (iNOS) were assessed. The major compounds found in HERP were liquiritigenin (68.8mg/g), formononetin (54.29mg/g), biochanin A (30.97mg/g), and daidzein (19.90mg/g). Rats treated with 10mg/kg HERP demonstrated significant decreases in MPO concentrations, gross and histological scores of tissue damage, and iNOS expression (p<0.05). Similarly, rats treated with 100mg/kg HERP demonstrated significant decreases in MPO levels (p<0.05) and histological scores of tissue damage (p<0.05). The results of this study indicate that oral administration of HERP attenuates AAIC in rats, which may be due to anti-inflammatory effects related to iNOS inhibition. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Transcriptome immunomodulation of in-feed additives in Atlantic salmon Salmo salar infested with sea lice Caligus rogercresseyi.

PubMed

Núñez-Acuña, Gustavo; Gonçalves, Ana Teresa; Valenzuela-Muñoz, Valentina; Pino-Marambio, Jorge; Wadsworth, Simon; Gallardo-Escárate, Cristian

2015-11-01

One of the most significant threats to the Chilean salmon aquaculture industry is the ectoparasitic sea louse Caligus rogercresseyi. To cope with sea lice infestations, functional diets have become an important component in strengthening the host immune response. The aim of this study was to evaluate molecular mechanisms activated through immunostimulation by in-feed plant-derived additives in Atlantic salmon infected with sea lice. Herein, a transcriptome-wide sequencing analysis was performed from skin and head kidney tissues, evidencing that the immune response genes were the most variable after the challenge, especially in the head kidney, while other genes involved in metabolism were highly expressed individuals fed with the immunostimulants. Interestingly, defensive enzymes such as Cytochrome p450 and serpins were down-regulated in infested individuals, especially in skin tissue. Additionally, MHC-I and MHC-II genes were differentially expressed after the incorporation of the in-feed additives, giving some cues about the protection mechanisms of plant-derived compound as immunostimulants for infested salmons. This is the first published study that evaluates the transcriptomic response of sea lice-infested Atlantic salmon fed with in-feed additives. Copyright © 2015 Elsevier Ltd. All rights reserved.

Agronomical, biochemical and histological response of resistant and susceptible wheat and barley under BYDV stress

PubMed Central

Choudhury, Shormin; Hu, Hongliang; Larkin, Philip; Meinke, Holger; Shabala, Sergey; Ahmed, Ibrahim

2018-01-01

Barley yellow dwarf virus-PAV (BYDV-PAV) is one of the major viruses causing a widespread and serious viral disease affecting cereal crops. To gain a better understanding of plant defence mechanisms of BYDV resistance genes (Bdv2 and RYd2) against BYDV-PAV infection, the differences in agronomical, biochemical and histological changes between susceptible and resistant wheat and barley cultivars were investigated. We found that root growth and total dry matter of susceptible cultivars showed greater reduction than that of resistant ones after infection. BYDV infected leaves in susceptible wheat and barley cultivars showed a significant reduction in photosynthetic pigments, an increase in the concentration of reducing sugar. The protein levels were also low in infected leaves. There was a significant increase in total phenol contents in resistant cultivars, which might reflect a protective mechanism of plants against virus infection. In phloem tissue, sieve elements (SE) and companion cells (CC) were severely damaged in susceptible cultivars after infection. It is suggested that restriction of viral movement in the phloem tissue and increased production of phenolic compounds may play a role in the resistance and defensive mechanisms of both Bdv2 and RYd2 against virus infection. PMID:29868264

Chlorogenic Acid Attenuates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting TLR4/NF-κB Signal Pathway.

PubMed

Ye, Han-Yang; Jin, Jian; Jin, Ling-Wei; Chen, Yan; Zhou, Zhi-Hong; Li, Zhan-Yuan

2017-04-01

Chlorogenic acid (CGA), a polyphenolic compound, exists widely in medicinal herbs, which has been shown a strong antioxidant and anti-inflammatory effect. This study investigated the protective effects and mechanism of CGA on lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Treatment of CGA successfully ameliorates LPS-induced renal function and pathological damage. Moreover, CGA dose-dependently suppressed LPS-induced blood urea nitrogen (BUN), creatinine levels, and inflammatory cytokines TNF-α, IL-6, and IL-1β in serum and tissue. The relative proteins' expression of TLR4/NF-κB signal pathway was assessed by western blot analysis. Our results showed that CGA dose-dependently attenuated LPS-induced kidney histopathologic changes, serum BUN, and creatinine levels. CGA also suppressed LPS-induced TNF-α, IL-6, and IL-1β production both in serum and kidney tissues. Furthermore, our results showed that CGA significantly inhibited the LPS-induced expression of phosphorylated NF-κB p65 and IκB as well as the expression of TLR4 signal. In conclusion, our results provide a mechanistic explanation for the anti-inflammatory effects of CGA in LPS-induced AKI mice through inhibiting TLR4/NF-κB signaling pathway.

Low hydrogen sulphide and chronic kidney disease: a dangerous liaison.

PubMed

Perna, Alessandra F; Ingrosso, Diego

2012-02-01

Hydrogen sulphide, H(2)S, is a gaseous compound involved in a number of biological responses, e.g. blood pressure, vascular function and energy metabolism. In particular, H(2)S is able to lower blood pressure, protect from injury in models of ischaemia-reperfusion and induce a hypometabolic state. In chronic kidney disease (CKD), low plasma hydrogen sulphide levels have been established in humans and in animal models. The enzymes involved in its production are cystathionine β-synthase, cystathionine γ-lyase and 3-mercaptopyruvate sulphurtransferase. The mechanisms for H(2)S decrease in CKD are related to the reduced gene expression (demonstrated in uraemic patient blood cells) and decreased protein levels (in tissues such as liver, kidney, brain in a CKD rat model). In the present Nephrol Dial Transplant issue, in fact, Aminzadeh and Vaziri document that the alterations in this pathway complicate the uraemic state and are linked to CKD progression. They furnish a time frame in CKD and record enzyme tissue distribution. It remains to be established if low H(2)S is causally linked to CKD progression and if interventions aimed to restore the status quo ante are able to modify this picture.

Transcriptome difference and potential crosstalk between liver and mammary tissue in mid-lactation primiparous dairy cows.

PubMed

Bu, Dengpan; Bionaz, Massimo; Wang, Mengzhi; Nan, Xuemei; Ma, Lu; Wang, Jiaqi

2017-01-01

Liver and mammary gland are among the most important organs during lactation in dairy cows. With the purpose of understanding both the different and the complementary roles and the crosstalk of those two organs during lactation, a transcriptome analysis was performed on liver and mammary tissues of 10 primiparous dairy cows in mid-lactation. The analysis was performed using a 4×44K Bovine Agilent microarray chip. The transcriptome difference between the two tissues was analyzed using SAS JMP Genomics using ANOVA with a false discovery rate correction (FDR). The analysis uncovered >9,000 genes differentially expressed (DEG) between the two tissues with a FDR<0.001. The functional analysis of the DEG uncovered a larger metabolic (especially related to lipid) and inflammatory response capacity in liver compared with mammary tissue while the mammary tissue had a larger protein synthesis and secretion, proliferation/differentiation, signaling, and innate immune system capacity compared with the liver. A plethora of endogenous compounds, cytokines, and transcription factors were estimated to control the DEG between the two tissues. Compared with mammary tissue, the liver transcriptome appeared to be under control of a large array of ligand-dependent nuclear receptors and, among endogenous chemical, fatty acids and bacteria-derived compounds. Compared with liver, the transcriptome of the mammary tissue was potentially under control of a large number of growth factors and miRNA. The in silico crosstalk analysis between the two tissues revealed an overall large communication with a reciprocal control of lipid metabolism, innate immune system adaptation, and proliferation/differentiation. In summary the transcriptome analysis confirmed prior known differences between liver and mammary tissue, especially considering the indication of a larger metabolic activity in liver compared with the mammary tissue and the larger protein synthesis, communication, and proliferative capacity in mammary tissue compared with the liver. Relatively novel is the indication by the data that the transcriptome of the liver is highly regulated by dietary and bacteria-related compounds while the mammary transcriptome is more under control of hormones, growth factors, and miRNA. A large crosstalk between the two tissues with a reciprocal control of metabolism and innate immune-adaptation was indicated by the network analysis that allowed uncovering previously unknown crosstalk between liver and mammary tissue for several signaling molecules.

Transcriptome difference and potential crosstalk between liver and mammary tissue in mid-lactation primiparous dairy cows

PubMed Central

Bu, Dengpan; Bionaz, Massimo; Wang, Mengzhi; Nan, Xuemei; Ma, Lu; Wang, Jiaqi

2017-01-01

Liver and mammary gland are among the most important organs during lactation in dairy cows. With the purpose of understanding both the different and the complementary roles and the crosstalk of those two organs during lactation, a transcriptome analysis was performed on liver and mammary tissues of 10 primiparous dairy cows in mid-lactation. The analysis was performed using a 4×44K Bovine Agilent microarray chip. The transcriptome difference between the two tissues was analyzed using SAS JMP Genomics using ANOVA with a false discovery rate correction (FDR). The analysis uncovered >9,000 genes differentially expressed (DEG) between the two tissues with a FDR<0.001. The functional analysis of the DEG uncovered a larger metabolic (especially related to lipid) and inflammatory response capacity in liver compared with mammary tissue while the mammary tissue had a larger protein synthesis and secretion, proliferation/differentiation, signaling, and innate immune system capacity compared with the liver. A plethora of endogenous compounds, cytokines, and transcription factors were estimated to control the DEG between the two tissues. Compared with mammary tissue, the liver transcriptome appeared to be under control of a large array of ligand-dependent nuclear receptors and, among endogenous chemical, fatty acids and bacteria-derived compounds. Compared with liver, the transcriptome of the mammary tissue was potentially under control of a large number of growth factors and miRNA. The in silico crosstalk analysis between the two tissues revealed an overall large communication with a reciprocal control of lipid metabolism, innate immune system adaptation, and proliferation/differentiation. In summary the transcriptome analysis confirmed prior known differences between liver and mammary tissue, especially considering the indication of a larger metabolic activity in liver compared with the mammary tissue and the larger protein synthesis, communication, and proliferative capacity in mammary tissue compared with the liver. Relatively novel is the indication by the data that the transcriptome of the liver is highly regulated by dietary and bacteria-related compounds while the mammary transcriptome is more under control of hormones, growth factors, and miRNA. A large crosstalk between the two tissues with a reciprocal control of metabolism and innate immune-adaptation was indicated by the network analysis that allowed uncovering previously unknown crosstalk between liver and mammary tissue for several signaling molecules. PMID:28291785

A new ferulic acid ester from Rhodiola wallichiana var. cholaensis (Crassulaceae).

PubMed

Song, Yaling; Zhou, Jianming; Wang, Xuejing; Xie, Xue; Zhao, Yiwu; Ni, Fuyong; Huang, Wenzhe; Wang, Zhenzhong; Xiao, Wei

2018-01-01

A new ferulic acid ester, 6-feruloyloxyhexanoic acid (1), was isolated along with 10 known ones (2-11), from the concentrated water extract of Rhodiola wallichiana var. cholaensis. Their chemical structures were elucidated on the basis of extensive spectroscopic methods including Two-dimensional nuclear magnetic resonance (2D NMR) experiments. Compound 3 was isolated from this plant for the first time. The protective effects against H 2 O 2 -induced myocardial cell injury in cultured H9c2 cells were also evaluated. Compounds 1, 5 and 7-11 provided significant protective effects on H 2 O 2 -induced H9c2 cells injury at the concentration of 25 μg/mL. And the protective effects of compound 1 was also investigated by the oxygen-glucose deprivation/reperfusion (OGD/R) tests.

[Obesity and heart].

PubMed

Svačina, Štěpán

2014-12-01

Cardiovascular complications of obesity are traditionally considered an important complication of obesity. Obesity itself is probably not direct cause of atherosclerosis or coronary heart disease. This may occur indirectly in metabolic complications of obesity, especially diabetes and metabolic syndrome. However, thrombogenicity potential of obesity contributes to embolism and atherosclerosis development. In cardiology is well-known a phenomenon of obesity paradox when obese patients have better prognosis than thin. This is the case of heart failure and some other cardiovascular diseases. Recently, a new concept has emerged of myokines - hormones from muscle tissue that have extensive protective effects on organism and probably on heart. Whether heart is a source of myokines is uncertain. However, undoubted importance has epicardial and pericardial fatty tissue. The epicardial fatty tissue has mainly protective effects on myocardium. This fatty tissue may produce factors of inflammation affecting the myocardium. Relationship between amount of epicardial fatty tissue and coronary heart disease is rather pathogenic. Currently, it is certain that obesity brings more metabolic and cancer complications than cardiovascular and accurate contribution to pathogenic or protective character of fatty tissue in cardiology requires further research. Nevertheless, the conclusion is that adipose tissue of organism and around the heart may be in some circumstances beneficial.

Predation and protection in the macroevolutionary history of conifer cones

PubMed Central

Leslie, Andrew B.

2011-01-01

Conifers are an excellent group in which to explore how changing ecological interactions may have influenced the allocation of reproductive tissues in seed plants over long time scales, because of their extensive fossil record and their important role in terrestrial ecosystems since the Palaeozoic. Measurements of individual conifer pollen-producing and seed-producing cones from the Pennsylvanian to the Recent show that the relative amount of tissue invested in pollen cones has remained constant through time, while seed cones show a sharp increase in proportional tissue investment in the Jurassic that has continued to intensify to the present day. Since seed size in conifers has remained similar through time, this increase reflects greater investment in protective cone tissues such as robust, tightly packed scales. This shift in morphology and tissue allocation is broadly concurrent with the appearance of new vertebrate groups capable of browsing in tree canopies, as well as a diversification of insect-feeding strategies, suggesting that an important change in plant–animal interactions occurred over the Mesozoic that favoured an increase in seed cone protective tissues. PMID:21345864

The therapeutic potential of erythropoiesis-stimulating agents for tissue protection: a tale of two receptors.

PubMed

Brines, Michael

2010-01-01

Erythropoietin (EPO) is a well-known therapeutic protein employed widely in the treatment of anemia. Over the past decade, abundant evidence has shown that in addition to its systemic role in the regulation of plasma pO(2) by modulating erythrocyte numbers, EPO is also a cytoprotective molecule made locally in response to injury or metabolic stress. Many studies have shown beneficial effects of EPO administration in reducing damage caused by ischemia-reperfusion, trauma, cytotoxicity, infection and inflammation in a variety of organs and tissues. Notably, the receptor mediating the nonerythropoietic effects of EPO differs from the one responsible for hematopoiesis. The tissue-protective receptor exhibits a lower affinity for EPO and is a heteromer consisting of EPO receptor monomers in association with the common receptor that is also employed by granulocyte macrophage colony-stimulating factor, interleukin 3, and interleukin 5. This heteromeric receptor is expressed immediately following injury, whereas EPO production is delayed. Thus, early administration of EPO can dramatically reduce the deleterious components of the local inflammatory cascade. However, a high dose of EPO is required and this also stimulates the bone marrow to produce highly reactive platelets and activates the vascular endothelium into a prothrombotic state. To circumvent these undesirable effects, the EPO molecule has been successfully altered to selectively eliminate erythropoietic and prothrombotic potencies, while preserving tissue-protective activities. Very recently, small peptide mimetics have been developed that recapitulate the tissue-protective activities of EPO. Nonerythropoietic tissue-protective molecules hold high promise in a wide variety of acute and chronic diseases. Copyright (c) 2010 S. Karger AG, Basel.

Design, Synthesis and Evaluation of a Novel Series of Inhibitors Reversing P-Glycoprotein-Mediated Multidrug Resistance.

PubMed

Ghaleb, Hesham; Li, Huilan; Kairuki, Mutta; Qiu, Qianqian; Bi, Xinzhou; Liu, Chunxia; Liao, Chen; Li, Jieming; Hezam, Kamal; Huang, Wenlong; Qian, Hai

2018-05-22

Multidrug resistance (MDR) is still the main barrier to attaining effective results with chemotherapy. Discovery of new chemo-reversal agents is needed to overcome MDR. Our study focused on a better way to obtain novel drugs with triazole rings that have an MDR-reversal ability through click chemistry. Among 20 developed compounds, compound 19 had a minimal cytotoxic effect compared to tariquidar and verapamil (VRP) and showed a higher reversal activity than VRP through increased accumulation in K562/A02 cells. Compound 19 also played an important role in the P-gp efflux function of intracellular Rh123 and doxorubicin (DOX) accumulation in K562/A02 cells. Moreover, compound 19 exhibited a long lifetime of approximately 24 h. These results indicated that compound 19 is a potential lead compound for the design of new drugs to overcome cancer MDR. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

21 CFR 346.50 - Labeling of anorectal drug products.

Code of Federal Regulations, 2011 CFR

2011-04-01

...., cream, lotion, or ointment).” (b) Indications. The labeling of the product states, under the heading... protective coating over inflamed tissues to help prevent drying of tissues.” (B) “Temporarily protects irritated areas.” (C) “Temporarily relieves burning.” (D) “Provides temporary relief from skin irritations...

The lipid lowering drug lovastatin protects against doxorubicin-induced hepatotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henninger, Christian; Institute of Toxicology, University Duesseldorf, Medical Faculty, Universitätsstrasse 1, D-40225 Duesseldorf; Huelsenbeck, Johannes

2012-05-15

Liver is the main detoxifying organ and therefore the target of high concentrations of genotoxic compounds, such as environmental carcinogens and anticancer drugs. Here, we investigated the usefulness of lovastatin, which is nowadays widely used for lipid lowering purpose, as a hepatoprotective drug following the administration of the anthracycline derivative doxorubicin in vivo. To this end, BALB/c mice were exposed to either a single high dose or three consecutive low doses of doxorubicin. Acute and subacute hepatotoxicities were analyzed with or without lovastatin co-treatment. Lovastatin protected the liver against doxorubicin-induced acute pro-inflammatory and pro-fibrotic stress responses as indicated by anmore » attenuated mRNA expression of tumor necrosis factor alpha (TNFα) and connective tissue growth factor (CTGF), respectively. Hepatoprotection by lovastatin was due to a reduced induction of DNA damage following doxorubicin treatment. The statin also mitigated subacute anthracycline-provoked hepatotoxicity as shown on the level of doxorubicin- and epirubicin-stimulated CTGF mRNA expression as well as histopathologically detectable fibrosis and serum concentration of marker enzymes of hepatotoxicity (GPT/GLDH). Kidney damage following doxorubicin exposure was not detectable under our experimental conditions. Moreover, lovastatin showed multiple inhibitory effects on doxorubicin-triggered hepatic expression of genes involved in oxidative stress response, drug transport, DNA repair, cell cycle progression and cell death. Doxorubicin also stimulated the formation of ceramides. Ceramide production, however, was not blocked by lovastatin, indicating that hepatoprotection by lovastatin is independent of the sphingolipid metabolism. Overall, the data show that lovastatin is hepatoprotective following genotoxic stress induced by anthracyclines. Based on the data, we hypothesize that statins might be suitable to lower hepatic injury following anthracycline-based anticancer therapy. -- Highlights: ► Normal tissue damage is the therapy limiting side effect of anthracyclines. ► The effect of lovastatin on doxorubicin-induced hepatic damage was analyzed in vivo. ► Lovastatin protects the liver against DNA damage induced by doxorubicin. ► Lovastatin protects against acute and subacute doxorubicin-induced hepatotoxicity. ► Hepatoprotection by lovastatin is independent of the shingolipid metabolism.« less

Paederia foetida Linn. inhibits adjuvant induced arthritis by suppression of PGE(2) and COX-2 expression via nuclear factor-κB.

PubMed

Kumar, Vikas; Al-Abbasi, F A; Ahmed, Danish; Verma, Amita; Mujeeb, Mohd; Anwar, Firoz

2015-05-01

The current investigation was undertaken to determine the anti-inflammatory and antioxidant effects of Paederia foetida Linn. (PF) along with its mechanism of action when implemented in tissue protection. HPTLC was used in the identification of the compound quercetin, while in vitro analysis confirmed the significance of the antioxidant and anti-inflammatory action of PF. We initially demonstrated the in vivo anti-inflammatory effect of PF, evaluating it against a variety of phlogistic agents as well as turpentine oil, prostaglandin and arachidonic acid. Groups of rats, fasted overnight, were treated as follows: Group I: normal control (vehicle), Group II: PF (100 mg kg(-1)), Group III: arthritic control (CFA only, 0.05 ml), Group IV, V, VI: CFA (0.05 ml) + PF (25, 50 and 100 mg kg(-1)) and Group VII: CFA (0.05 ml) + indomethacin (10 mg per kg b.w.). PF significantly protected against paw edema, arthritic index and body weight alteration induced by Complete Fruend's Adjuvant (CFA). Other observations, like histological and macroscopic changes, were observed in CFA induced inflammation in knee joints. Subcutaneous administration of CFA was accompanied by proinflammatory cytokine status, as appraised by the amplification of interleukin-2 (IL-2), interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α); oxidative stress status was estimated by the enhancement of the level of lipid peroxidation (LPO) and the depletion of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH). Pre-treatment with PF significantly (P < 0.001) protected against CFA induced oxidative stress and proinflammatory cytokines. More prominently, CFA administration augmented tissue and plasma superoxide (O2) and hydrogen peroxide (H2O2) levels, while the PF pre-treatment significantly (P < 0.001) reversed all CFA induced intracellular interruption. Following CFA induced arthritis, PF was tested for its free radical scavenging activity against the DPPH and ABTS radicals and its inhibitory proficiency against COX-1 and COX-2 in vitro. Considering the above, the current research confirmed momentous protection against CFA induced arthritis, which could be attributed to its anti-inflammatory and pro-oxidant nature.

Chemical composition of the Lippia origanoides essential oils and their antigenotoxicity against bleomycin-induced DNA damage.

PubMed

Vicuña, Gloria Carolina; Stashenko, Elena E; Fuentes, Jorge Luis

2010-07-01

The present work evaluated the chemical composition of the essential oils (EO) obtained from Lippia origanoides and their DNA protective effect against bleomycin-induced genotoxicity. L. origanoides EO chemical composition was determined by gas chromatography-mass spectrometry (GC-MS). The major compounds of the L. origanoides EOs were thymol (34-58%) and carvacrol (26%). The antigenotoxic effects of the EOs, major compounds and standard compound (epigallocatechin gallate) were assayed in co-incubation procedures using the SOS chromotest in Escherichia coli. Both EOs and their major compounds protected bacterial cells against bleomycin-induced genotoxicity indicating that these two compounds were principally responsible for the antigenotoxicity detected in the oils. Thymol and carvacrol antigenotoxicity was lower than those observed with epigallocatechin gallate. The results were discussed in relation to the chemopreventive potential of L. origanoides EOs and their major components, carvacrol and thymol. Copyright 2009 Elsevier B.V. All rights reserved.

Evaluation of chlorpyrifos toxicity through a 28-day study: Cholinesterase activity, oxidative stress responses, parent compound/metabolite levels, and primary DNA damage in blood and brain tissue of adult male Wistar rats.

PubMed

Kopjar, Nevenka; Žunec, Suzana; Mendaš, Gordana; Micek, Vedran; Kašuba, Vilena; Mikolić, Anja; Lovaković, Blanka Tariba; Milić, Mirta; Pavičić, Ivan; Čermak, Ana Marija Marjanović; Pizent, Alica; Lucić Vrdoljak, Ana; Želježić, Davor

2018-01-05

In this 28 day-study, we evaluated the effects of the insecticide chlorpyrifos orally administered to Wistar rats at doses 0.160, 0.015, and 0.010 mg/kg b. w./day. Following treatment, total cholinesterase activity and activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were measured. Oxidative stress responses were evaluated using a battery of endpoints to establish lipid peroxidation, changes in total antioxidant capacity, level of reactive oxygen species (ROS), glutathione (GSH) level and activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase. Using HPLC-UV DAD analysis, levels of the parent compound and its main metabolite 3,5,6-trichloro-2-pyridinol in plasma and brain tissue were measured. The genotoxic effect was estimated using alkaline comet assay in leukocytes and brain tissue. The exposure did not result in significant effects on total cholinesterase, AChE and BChE activity in plasma and brain tissue. Lipid peroxidation slightly increased both in plasma and brain tissue. Total antioxidant capacity, ROS and GSH levels were marginally influenced by the exposure. Treatment led to significant increases of GSH-Px activity in blood, SOD activity in erythrocytes and a slight increase of catalase activity in plasma. HPLC-UV DAD analysis revealed the presence of both the parent compound and its main metabolite in the plasma of all of the experimental animals and brain tissue of the animals treated at the two higher doses. All of the tested doses of chlorpyrifos were slightly genotoxic, both to leukocytes and brain tissue. Our results call for further research using other sensitive biomarkers of effect, along with different exposure scenarios. Copyright © 2017 Elsevier B.V. All rights reserved.

A reconnaissance study of halogenated organic compounds in catfish from the lower Mississippi river and its major tributaries

USGS Publications Warehouse

Leiker, T.J.; Rostad, C.E.; Barnes, C.R.; Pereira, W.E.

1991-01-01

Blue catfish, (Ictarurus furcatus), black bullhead catfish, (Ictalurus melas), channel catfish (Ictalurus punctatus), and flathead catfish (Pylodictus olivaris), were collected along a 1200 mile river reach of the Mississippi River and its major tributaries. Tissue samples were extracted and analyzed by fused silica capillary gas chromatography/mass spectrometry (GC/MS) to determine the concentrations of hydrophobic organic halogenated contaminants that have bioconcentrated within the tissues. The compounds identified in the tissue include chlordane, polychlorinated biphenyls (PCBs), DDT and its metabolites along with several other chlorinated pesticides. The data indicates that the southern reach of the river system appears to be more contaminated than the middle and upper reaches of the study area.

MnTnBuOE-2-PyP protects normal colorectal fibroblasts from radiation damage and simultaneously enhances radio/chemotherapeutic killing of colorectal cancer cells

PubMed Central

Kosmacek, Elizabeth A.; Chatterjee, Arpita; Tong, Qiang; Lin, Chi; Oberley, Rebecca E.

2016-01-01

Manganese porphyrins have been shown to be potent radioprotectors in a variety of cancer models. However, the mechanism as to how these porphyrins protect normal tissues from radiation damage still remains largely unknown. In the current study, we determine the effects of the manganese porphyrin, MnTnBuOE-2-PyP, on primary colorectal fibroblasts exposed to irradiation. We found that 2 Gy of radiation enhances the fibroblasts' ability to contract a collagen matrix, increases cell size and promotes cellular senesence. Treating fibroblasts with MnTnBuOE-2-PyP significantly inhibited radiation-induced collagen contraction, preserved cell morphology and also inhibited cellular senescence. We further showed that MnTnBuOE-2-PyP enhanced the overall viability of the fibroblasts following exposure to radiation but did not protect colorectal cancer cell viability. Specifically, MnTnBuOE-2-PyP in combination with irradiation, caused a significant decrease in tumor clonogenicity. Since locally advanced rectal cancers are treated with chemoradiation therapy followed by surgery and non-metastatic anal cancers are treated with chemoradiation therapy, we also investigated the effects of MnTnBuOE-2-PyP in combination with radiation, 5-fluorouracil with and without Mitomycin C. We found that MnTnBuOE-2-PyP in combination with Mitomycin C or 5-fluorouracil further enhances those compounds' ability to suppress tumor cell growth. When MnTnBuOE-2-PyP was combined with the two chemotherapeutics and radiation, we observed the greatest reduction in tumor cell growth. Therefore, these studies indicate that MnTnBuOE-2-PyP could be used as a potent radioprotector for normal tissue, while at the same time enhancing radiation and chemotherapy treatment for rectal and anal cancers. PMID:27119354

MnTnBuOE-2-PyP protects normal colorectal fibroblasts from radiation damage and simultaneously enhances radio/chemotherapeutic killing of colorectal cancer cells.

PubMed

Kosmacek, Elizabeth A; Chatterjee, Arpita; Tong, Qiang; Lin, Chi; Oberley-Deegan, Rebecca E

2016-06-07

Manganese porphyrins have been shown to be potent radioprotectors in a variety of cancer models. However, the mechanism as to how these porphyrins protect normal tissues from radiation damage still remains largely unknown. In the current study, we determine the effects of the manganese porphyrin, MnTnBuOE-2-PyP, on primary colorectal fibroblasts exposed to irradiation. We found that 2 Gy of radiation enhances the fibroblasts' ability to contract a collagen matrix, increases cell size and promotes cellular senesence. Treating fibroblasts with MnTnBuOE-2-PyP significantly inhibited radiation-induced collagen contraction, preserved cell morphology and also inhibited cellular senescence. We further showed that MnTnBuOE-2-PyP enhanced the overall viability of the fibroblasts following exposure to radiation but did not protect colorectal cancer cell viability. Specifically, MnTnBuOE-2-PyP in combination with irradiation, caused a significant decrease in tumor clonogenicity. Since locally advanced rectal cancers are treated with chemoradiation therapy followed by surgery and non-metastatic anal cancers are treated with chemoradiation therapy, we also investigated the effects of MnTnBuOE-2-PyP in combination with radiation, 5-fluorouracil with and without Mitomycin C. We found that MnTnBuOE-2-PyP in combination with Mitomycin C or 5-fluorouracil further enhances those compounds' ability to suppress tumor cell growth. When MnTnBuOE-2-PyP was combined with the two chemotherapeutics and radiation, we observed the greatest reduction in tumor cell growth. Therefore, these studies indicate that MnTnBuOE-2-PyP could be used as a potent radioprotector for normal tissue, while at the same time enhancing radiation and chemotherapy treatment for rectal and anal cancers.

Ferulic acid photoprotective properties in association with UV filters: multifunctional sunscreen with improved SPF and UVA-PF.

PubMed

Peres, Daniela D'Almeida; Sarruf, Fernanda Daud; de Oliveira, Camila Areias; Velasco, Maria Valéria Robles; Baby, André Rolim

2018-05-26

Ultraviolet (UV) radiation stimulates several injurious biological effects on cutaneous tissue, causing, for instance, photocarcinogenesis. Sunscreens are topical products designed to protect the skin against these harmful effects and their use must be encouraged. The addition of antioxidants, as ferulic acid (FA), a phenolic compound from the class of the hydroxycinnamic acids, in sunscreens could improve their sun protection factor (SPF) and prevent inflammatory reactions. Here, the clinical safety and efficacy of an association of ethylhexyl triazone and bis-ethylhexyloxyphenol methoxyphenyl triazine (UV filters) with ferulic acid were assessed. Samples had good skin biocompatibility and presented satisfactory safety profile, even in a sun-exposed condition. A synergic effect between the natural polyphenol and the UV filters was evidenced, as well as, FA increased in vivo SPF in 37% and the UVA protection factor (UVA-PF) in 26%. The in vivo data indicated that FA reinforced the broad-spectrum characteristic of the photoprotective formulations. Additionally, according to the results from the ex vivo antioxidant test, it is plausible to recommend adjustments on the ex vivo protocol to explicitly determine the positive effects of topical antioxidant ingredients applied over the skin. These results provided a new perspective for the development of multifunctional bioactive sunscreens using FA as a new platform. Copyright © 2018 Elsevier B.V. All rights reserved.

Homestead Valley, California, aftershocks (March 17-18, 1979) recorded on portable seismographs

USGS Publications Warehouse

Perry-Huston, Sue; Eberhart-Phillips, Donna

1994-01-01

A method for the determination of chlorinated organic compounds in aquatic tissue by dual capillary-column gas chromatography with electron- capture detection is described. Whole-body-fish or corbicula tissue is homogenized, Soxhlet extracted, lipid removed by gel permeation chromatography, and fractionated using alumina/silica adsorption chromatography. The extracts are analyzed by dissimilar capillary-column gas chromatography with electron-capture detection. The method reporting limits are 5 micrograms per kilogram (ug/kg) for chlorinated compounds, 50 ug/kg for polychlorinated biphenyls, and 200 ug/kg for toxaphene.

High-resolution x-ray absorption spectroscopy studies of metal compounds in neurodegenerative brain tissue

NASA Astrophysics Data System (ADS)

Collingwood, J. F.; Mikhaylova, A.; Davidson, M. R.; Batich, C.; Streit, W. J.; Eskin, T.; Terry, J.; Barrea, R.; Underhill, R. S.; Dobson, J.

2005-01-01

Fluorescence mapping and microfocus X-ray absorption spectroscopy are used to detect, locate and identify iron biominerals and other inorganic metal accumulations in neurodegenerative brain tissue at sub-cellular resolution (<5 microns). Recent progress in developing the technique is reviewed. Synchrotron X-rays are used to map tissue sections for metals of interest, and XANES and XAFS are used to characterise anomalous concentrations of the metals in-situ so that they can be correlated with tissue structures and disease pathology. Iron anomalies associated with biogenic magnetite, ferritin and haemoglobin are located and identified in an avian tissue model with a pixel resolution ~5 microns. Subsequent studies include brain tissue sections from transgenic Huntington's mice, and the first high-resolution mapping and identification of iron biominerals in human Alzheimer's and control autopsy brain tissue. Technical developments include use of microfocus diffraction to obtain structural information about biominerals in-situ, and depositing sample location grids by lithography for the location of anomalies by conventional microscopy. The combined techniques provide a breakthrough in the study of both intra- and extra-cellular iron compounds and related metals in tissue. The information to be gained from this approach has implications for future diagnosis and treatment of neurodegeneration, and for our understanding of the mechanisms involved.

Wide-range screening of anti-inflammatory compounds in tomato using LC-MS and elucidating the mechanism of their functions

PubMed Central

Mohri, Shinsuke; Takahashi, Haruya; Sakai, Maiko; Takahashi, Shingo; Waki, Naoko; Aizawa, Koichi; Suganuma, Hiroyuki; Ara, Takeshi; Matsumura, Yasuki; Shibata, Daisuke; Goto, Tsuyoshi; Kawada, Teruo

2018-01-01

Obesity-induced chronic inflammation is a key factor in type 2 diabetes. A vicious cycle involving pro-inflammatory mediators between adipocytes and macrophages is a common cause of chronic inflammation in the adipose tissue. Tomato is one of the most popular vegetables and is associated with a reduced risk of diabetes. However, the molecular mechanism underlying the effect of tomato on diabetes is unclear. In this study, we focused on anti-inflammatory compounds in tomato. We found that the extract of tomato reduced plasma glucose and inflammatory markers in mice. We screened anti-inflammatory fractions in tomato using lipopolysaccharide-stimulated RAW264.7 macrophages, and active compounds were estimated by liquid chromatography-mass spectrometry over a wide range. Surprisingly, a large number of compounds including oxylipin and coumarin derivatives were estimated as anti-inflammatory compounds. Especially, 9-oxo-octadecadienoic acid and daphnetin suppressed pro-inflammatory cytokines in RAW264.7 macrophages inhibiting mitogen-activated protein kinase phosphorylation and inhibitor of kappa B α protein degradation. These findings suggest that tomato containing diverse anti-inflammatory compounds ameliorates chronic inflammation in obese adipose tissue. PMID:29329333

40 CFR 721.3320 - Ethanol, 2-amino-, com-pound with N-hydroxy-N-nitro-soben-zena-mine (1:1).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Ethanol, 2-amino-, com-pound with N... Significant New Uses for Specific Chemical Substances § 721.3320 Ethanol, 2-amino-, com-pound with N-hydroxy-N...) The chemical substance identified as ethanol, 2-amino-, compound with N-hydroxy-N-nitrosobenzenamine...

40 CFR 721.3320 - Ethanol, 2-amino-, com-pound with N-hydroxy-N-nitro-soben-zena-mine (1:1).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Ethanol, 2-amino-, com-pound with N... Significant New Uses for Specific Chemical Substances § 721.3320 Ethanol, 2-amino-, com-pound with N-hydroxy-N...) The chemical substance identified as ethanol, 2-amino-, compound with N-hydroxy-N-nitrosobenzenamine...

40 CFR 721.3320 - Ethanol, 2-amino-, com-pound with N-hydroxy-N-nitro-soben-zena-mine (1:1).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Ethanol, 2-amino-, com-pound with N... Significant New Uses for Specific Chemical Substances § 721.3320 Ethanol, 2-amino-, com-pound with N-hydroxy-N...) The chemical substance identified as ethanol, 2-amino-, compound with N-hydroxy-N-nitrosobenzenamine...

40 CFR 721.3320 - Ethanol, 2-amino-, com-pound with N-hydroxy-N-nitro-soben-zena-mine (1:1).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Ethanol, 2-amino-, com-pound with N... Significant New Uses for Specific Chemical Substances § 721.3320 Ethanol, 2-amino-, com-pound with N-hydroxy-N...) The chemical substance identified as ethanol, 2-amino-, compound with N-hydroxy-N-nitrosobenzenamine...

40 CFR 721.3320 - Ethanol, 2-amino-, com-pound with N-hydroxy-N-nitro-soben-zena-mine (1:1).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Ethanol, 2-amino-, com-pound with N... Significant New Uses for Specific Chemical Substances § 721.3320 Ethanol, 2-amino-, com-pound with N-hydroxy-N...) The chemical substance identified as ethanol, 2-amino-, compound with N-hydroxy-N-nitrosobenzenamine...

Transcription Factor-Mediated Control of Anthocyanin Biosynthesis in Vegetative Tissues1[OPEN

PubMed Central

Outchkourov, Nikolay S.; Schrama, Xandra; Blilou, Ikram; Jongedijk, Esmer; Simon, Carmen Diez; Bosch, Dirk; Hall, Robert D.

2018-01-01

Plants accumulate secondary metabolites to adapt to environmental conditions. These compounds, here exemplified by the purple-colored anthocyanins, are accumulated upon high temperatures, UV-light, drought, and nutrient deficiencies, and may contribute to tolerance to these stresses. Producing compounds is often part of a more broad response of the plant to changes in the environment. Here we investigate how a transcription-factor-mediated program for controlling anthocyanin biosynthesis also has effects on formation of specialized cell structures and changes in the plant root architecture. A systems biology approach was developed in tomato (Solanum lycopersicum) for coordinated induction of biosynthesis of anthocyanins, in a tissue- and development-independent manner. A transcription factor couple from Antirrhinum that is known to control anthocyanin biosynthesis was introduced in tomato under control of a dexamethasone-inducible promoter. By application of dexamethasone, anthocyanin formation was induced within 24 h in vegetative tissues and in undifferentiated cells. Profiles of metabolites and gene expression were analyzed in several tomato tissues. Changes in concentration of anthocyanins and other phenolic compounds were observed in all tested tissues, accompanied by induction of the biosynthetic pathways leading from Glc to anthocyanins. A number of pathways that are not known to be involved in anthocyanin biosynthesis were observed to be regulated. Anthocyanin-producing plants displayed profound physiological and architectural changes, depending on the tissue, including root branching, root epithelial cell morphology, seed germination, and leaf conductance. The inducible anthocyanin-production system reveals a range of phenomena that accompanies anthocyanin biosynthesis in tomato, including adaptions of the plants architecture and physiology. PMID:29192027

Flower-specific jasmonate signaling regulates constitutive floral defenses in wild tobacco

PubMed Central

Li, Ran; Wang, Ming; Wang, Yang; Schuman, Meredith C.; Weinhold, Arne; Schäfer, Martin; Jiménez-Alemán, Guillermo H.; Barthel, Andrea; Baldwin, Ian T.

2017-01-01

Optimal defense (OD) theory predicts that within a plant, tissues are defended in proportion to their fitness value and risk of predation. The fitness value of leaves varies greatly and leaves are protected by jasmonate (JA)-inducible defenses. Flowers are vehicles of Darwinian fitness in flowering plants and are attacked by herbivores and pathogens, but how they are defended is rarely investigated. We used Nicotiana attenuata, an ecological model plant with well-characterized herbivore interactions to characterize defense responses in flowers. Early floral stages constitutively accumulate greater amounts of two well-characterized defensive compounds, the volatile (E)-α-bergamotene and trypsin proteinase inhibitors (TPIs), which are also found in herbivore-induced leaves. Plants rendered deficient in JA biosynthesis or perception by RNA interference had significantly attenuated floral accumulations of defensive compounds known to be regulated by JA in leaves. By RNA-seq, we found a JAZ gene, NaJAZi, specifically expressed in early-stage floral tissues. Gene silencing revealed that NaJAZi functions as a flower-specific jasmonate repressor that regulates JAs, (E)-α-bergamotene, TPIs, and a defensin. Flowers silenced in NaJAZi are more resistant to tobacco budworm attack, a florivore. When the defensin was ectopically expressed in leaves, performance of Manduca sexta larvae, a folivore, decreased. NaJAZi physically interacts with a newly identified NINJA-like protein, but not the canonical NINJA. This NINJA-like recruits the corepressor TOPLESS that contributes to the suppressive function of NaJAZi on floral defenses. This study uncovers the defensive function of JA signaling in flowers, which includes components that tailor JA signaling to provide flower-specific defense. PMID:28784761

Ultrasound-assisted extraction of phenolic compounds from Cratoxylum formosum ssp. formosum leaves using central composite design and evaluation of its protective ability against H2O2-induced cell death.

PubMed

Yingngam, Bancha; Monschein, Marlene; Brantner, Adelheid

2014-09-01

To optimize the processing parameters for phenolic compounds extracted from Cratoxylum formosum ssp. formosum leaves using an ultrasound-assisted extraction and to evaluate its protective ability against H2O2-induced cell death. The influence of three independent variables including ethanol concentration (%), extraction temperature (°C) and extraction time (min) on the extraction yield of phenolic compounds were optimized using a central composite design-based response surface methodology. The obtained extract was assessed for its antioxidant activity by DPPH(•) and ABTS(•)(+) methods. Cellular protective ability against H2O2-induced cell death was evaluated on HEK293 cells using the MTT assay. The optimal conditions to achieve maximal yields of phenolic compounds were ethanol concentration of 50.33% (v/v), temperature of 65 °C, and extractiontion time of 15 min. The yield of phenolic compounds was (40.00±1.00) mg gallic acid equivalent/g dry powder which matched well with the values predicted from the proposed model. These conditions resulted in a higher efficiency concerning the extraction of phenolics compared to a conventional heat reflux extraction by providing shorter extraction time and reduced energy consumption. 5-O-caffeoylquinic acid identified by high performance liquid chromatography-diode array detector-electron spin ionization-mass spectrometry was the major compound in the obtained extract [(41.66±0.07) mg/g plant extract]. The obtained extract showed a strong ability to scavenge both DPPH(•) and ABTS(•)(+) free radicals and exhibited additionally good ability to protect HEK293 cells death against oxidative stress. These results indicate the suitability of ultrasound-assisted extraction for the extraction of phenolic compounds from Cratoxylum formosum ssp. formosum leaves. This phenolic-enriched extract can be used as valuable antioxidant source for health benefits. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Synthesis and biological activity of acetyl-protected hydroxybenzyl diethyl phosphates (EHBP) as potential chemotherapeutic agents.

PubMed

Kodela, Ravinder; Chattopadhyay, Mitali; Nath, Niharika; Cieciura, Lucyna Z; Pospishill, Liliya; Boring, Daniel; Crowell, James A; Kashfi, Khosrow

2011-12-01

Several acetyl-protected hydroxybenzyl diethyl phosphates (EHBPs) that are capable of forming quinone methide intermediates were synthesized and their cell growth inhibitory properties were evaluated in four different human cancer cell lines. Compounds 1, 1a, and 1b, corresponding to (4-acetyloxybenzyl diethylphosphate), (3-methyl-4-acetyloxybenzyl diethylphosphate), and (3-chloro-4-acetyloxybenzyl diethylphosphate), were significantly more potent than compounds 2 and 3, (2-acetyloxybenzyl diethylphosphate) and (3-acetyloxybenzyl diethylphosphate), respectively. Using HT-29 human colon cancer cells, compounds 1 and 3 increased apoptosis, inhibited proliferation, and caused a G(2)/M block in the cell cycle. Our data suggest that these compounds merit further investigation as potential anti-cancer agents. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Health effects of sour cherries with unique polyphenolic composition in their fruits].

PubMed

Hegedűs, Attila; Papp, Nóra; Blázovics, Anna; Stefanovitsné Bányai, Éva

2018-05-01

Health effects of fruit consumption are confirmed by many studies. Such effects are attributed to the polyphenolic compounds accumulating in fruit skin and mesocarp tissues. They contribute to the regulation on transcriptional, post-transcriptional and epigenetic levels. Since people consume much less fruits than the recommended quantities, a new approach includes the promotion of super fruits that are extremely rich sources of specific health compounds. A comparative analysis of Hungarian stone fruit cultivars detected a huge variability in fruit in vitro antioxidant capacity and total polyphenolic content. Two outstanding sour cherry cultivars ('Pipacs 1' and 'Fanal') were identified to accumulate elevated levels of polyphenolic compounds in their fruits. Sour cherries with different polyphenolic compositions were tested against alimentary induced hyperlipidemia using male Wistar rat model. Consumption of cherry fruit had different consequences for different cultivars: consumption of 'Pipacs 1' and 'Fanal' fruits resulted in 30% lower total cholesterol levels in the sera of hyperlipidemic animals after only 10 days of treatment. However, the consumption of 'Újfehértói fürtös' fruit has not induced significant alterations in the same parameter. Other lipid parameters also reflected the short-term beneficial effects of 'Pipacs 1' and 'Fanal' fruits. We suggest that not only some tropical and berry fruits might be considered as super fruits but certain genotypes of stone fruits as well. These have indeed marked physiological effects. Since 'Pipacs 1' and 'Fanal' are rich sources of colourless polyphenolics (e.g., phenolic acids and isoflavonoids) and anthocyanins, respectively, the protective effects associated with their consumption can be attributed to different polyphenolic compounds. Orv Hetil. 2018; 159(18): 720-725.

Fruit development, growth, and stored reserves in macauba palm (Acrocomia aculeata), an alternative bioenergy crop.

PubMed

Montoya, Sebastián Giraldo; Motoike, Sérgio Yoshimitsu; Kuki, Kacilda Naomi; Couto, Adriano Donato

2016-10-01

Main conclusion Macauba palm fruiting is supra-annual, and the fruit growth follows a double sigmoidal trend. The prevailing compound in the mesocarp differs as the fruit ages, oil being the major storage compound. Acrocomia aculeata, macauba palm, is a conspicuous species in the tropical Americas. Because the species is highly productive in oil-rich fruits, it is the subject of domestication as an alternative vegetable oil crop, especially as a bioenergy feedstock. This detailed study first presents the macauba fruit growth and development patterns, morphological changes and accumulation of organic compounds. Fruits were monitored weekly in a natural population. The fruiting was supra-annual, and the fruit growth curve followed a double sigmoidal trend with four stages (S): SI-slow growth and negligible differentiation of the fruit inner parts; SII-first growth spurt and visible, but not complete, differentiation of the inner parts; SIII-growth slowed down and all structures attained differentiation; and SIV-second growth spurt and fruit maturation. In SII, the exocarp and endocarp were the main contributors to fruit growth, whereas the mesocarp and endosperm were responsible for most of the weight gain during SIV. In comparison with starch and oil, soluble sugars did not accumulate in the mesocarp. However, starch was transitory and fueled the oil synthesis. The protective layers, the exocarp and endocarp, fulfilling their ecological roles, were the first to reach maturity, followed by the storage tissues, the mesocarp, and endosperm. The amount and nature of organic compounds in the mesocarp varied with the fruit development and growth stages, and oil was the main and final storage material. The description of macauba fruit's transformations and their temporal order may be of importance for future ecological and agronomical references.

Toxicology and metabolism of nickel compounds: comprehensive report of overall activities during the three-year period from December 1, 1977 to November 30, 1980

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sunderman, Jr, F W

1980-08-15

The main research accomplishments during the past three years are summarized. The principle areas of investigation are: 1. embryotoxicity, teratogenicity, and mutagenicity of nickel carbonyl; 2. metabolism, detoxification, and excretion of nickel compounds; 3. studies of nickel carcinogenesis; 4. nickel analysis in body fluids and tissues to monitor occupational exposures; 5. nephrotoxicity of nickel compounds; and 6. hematological effects of nickel compounds. (ACR)

Methods for boron delivery to mammalian tissue

DOEpatents

Hawthorne, M. Frederick; Feaks, Debra A.; Shelly, Kenneth J.

2003-01-01

Boron neutron capture therapy can be used to destroy tumors. This treatment modality is enhanced by delivering compounds to the tumor site where the compounds have high concentrations of boron, the boron compounds being encapsulated in the bilayer of a liposome or in the bilayer as well as the internal space of the liposomes. Preferred compounds, include carborane units with multiple boron atoms within the carborane cage structure. Liposomes with increased tumor specificity may also be used.

Geraniol-a flavoring agent with multifunctional effects in protecting the gastric and duodenal mucosa.

PubMed

de Carvalho, Katharinne Ingrid Moraes; Bonamin, Flavia; Dos Santos, Raquel Cássia; Périco, Larissa Lucena; Beserra, Fernando Pereira; de Sousa, Damião Pergentino; Filho, José Maria Barbosa; da Rocha, Lucia Regina Machado; Hiruma-Lima, Clelia Akiko

2014-04-01

Geraniol is an acyclic monoterpene alcohol commonly used as a flavoring agent. The present study was undertaken to investigate antiulcerogenic effects of geraniol and to determine the possible mechanisms involved in this action. In the model of the ethanol-induced ulcer, treatment of rats with geraniol by oral route significantly inhibited gastric lesions by 70 % (7.50 mg/kg) to 99 % (200 mg/kg). Analysis of the gastric tissue of rats treated with geraniol (7.50 mg/kg) revealed that total glutathione content levels (GSH) increased and levels of myeloperoxidase (MPO) decreased in the gastric mucosa. Oral treatment with geraniol significantly decreased the number of ulcerative lesions induced by ischemia/reperfusion injury by 71 % and the duodenal ulcers induced by cysteamine by 68 %. The action of geraniol was mediated by the activation of defensive mucosa-protective factors such as the nitric oxide (NO) pathway, endogenous prostaglandins, increased mucus production, increased sulfhydryl compounds, antioxidant properties and the stimulation of calcitonin gene-related peptide (CGRP) release through the activation of transient receptor potential vanilloid (TRPV). The multifaceted gastroprotective mechanisms of geraniol represent a promising option for the treatment of gastric and duodenal mucosa injury.

Polyphenols as Modulators of Aquaporin Family in Health and Disease.

PubMed

Fiorentini, Diana; Zambonin, Laura; Dalla Sega, Francesco Vieceli; Hrelia, Silvana

2015-01-01

Polyphenols are bioactive molecules widely distributed in fruits, vegetables, cereals, and beverages. Polyphenols in food sources are extensively studied for their role in the maintenance of human health and in the protection against development of chronic/degenerative diseases. Polyphenols act mainly as antioxidant molecules, protecting cell constituents against oxidative damage. The enormous number of polyphenolic compounds leads to huge different mechanisms of action not fully understood. Recently, some evidence is emerging about the role of polyphenols, such as curcumin, pinocembrin, resveratrol, and quercetin, in modulating the activity of some aquaporin (AQP) isoforms. AQPs are integral, small hydrophobic water channel proteins, extensively expressed in many organs and tissues, whose major function is to facilitate the transport of water or glycerol over cell plasma membranes. Here we summarize AQP physiological functions and report emerging evidence on the implication of these proteins in a number of pathophysiological processes. In particular, this review offers an overview about the role of AQPs in brain, eye, skin diseases, and metabolic syndrome, focusing on the ability of polyphenols to modulate AQP expression. This original analysis can contribute to elucidating some peculiar effects exerted by polyphenols and can lead to the development of an innovative potential preventive/therapeutic strategy.

Cyanidin and cyanidin 3-O-beta-D -glucoside as DNA cleavage protectors and antioxidants.

PubMed

Acquaviva, R; Russo, A; Galvano, F; Galvano, G; Barcellona, M L; Li Volti, G; Vanella, A

2003-08-01

Anthocyanins, colored flavonoids, are water-soluble pigments present in the plant kingdom; in fact they are secondary plant metabolites responsible for the blue, purple, and red color of many plant tissues. Present in beans, fruits, vegetables and red wines, considerable amounts of anthocyanins are ingested as constituents of the human diet (180-215 mg daily). There is now increasing interest in the in vivo protective function of natural antioxidants contained in dietary plants against oxidative damage caused by free radical species. Recently, the antioxidant activity of phenolic phytochemicals, has been investigated. Since the antioxidant mechanism of anthocyanin pigments is still controversial, in the present study we evaluated the effects of cyanidin and cyanidin 3-O-beta-D-glucoside on DNA cleavage, on their free radical scavenging capacity and on xanthine oxidase activity. Cyanidin and cyanidin 3-O-beta-D-glucoside showed a protective effect on DNA cleavage, a dose-dependent free radical scavenging activity and significant inhibition of XO activity. These effects suggest that anthocyanins exhibit interesting antioxidant properties, and could therefore represent a promising class of compounds useful in the treatment of pathologies where free radical production plays a key role.

One-electron oxidation of ergothioneine and analogues investigated by pulse radiolysis: redox reaction involving ergothioneine and vitamin C.

PubMed Central

Asmus, K D; Bensasson, R V; Bernier, J L; Houssin, R; Land, E J

1996-01-01

Redox reactions of endogenous and exogenous sulphur-containing compounds are involved in protection against oxidative damage arising from the incidence and/or treatment of many diseases, including cancer. We have investigated, via pulse radiolysis, the one-electron oxidation of ergothioneine, a molecule with antioxidant properties which is detected at millimolar concentrations in certain tissues and fluids subject to oxidative stress, including erythrocytes and plasma. The spectrum of the transient species, assigned to the product of one-electron oxidation, observed after reaction of ergothioneine with the oxidizing radicals OH., N3. and CCl3O2. has a maximum absorption at 520 nm and is very similar to that obtained by oxidation of analogous molecules such as 2-mercaptoimidazole, 1-methyl-2-mercaptoimidazole, S-methyl- and S,N-dimethyl-ergothioneine. In the presence of vitamin C, the oxidized form of ergothioneine is repaired by a rapid reduction (k = 6.3 x 10(8) M(-1).s(-1)) producing ascorbyl radicals. This co-operative interaction between ergothionine and ascorbate, similar to that previously observed between vitamin E and ascorbate, may contribute to essential biological redox protection. PMID:8615839

Human milk inactivates pathogens individually, additively, and synergistically.

PubMed

Isaacs, Charles E

2005-05-01

Breast-feeding can reduce the incidence and the severity of gastrointestinal and respiratory infections in the suckling neonate by providing additional protective factors to the infant's mucosal surfaces. Human milk provides protection against a broad array of infectious agents through redundancy. Protective factors in milk can target multiple early steps in pathogen replication and target each step with more than one antimicrobial compound. The antimicrobial activity in human milk results from protective factors working not only individually but also additively and synergistically. Lipid-dependent antimicrobial activity in milk results from the additive activity of all antimicrobial lipids and not necessarily the concentration of one particular lipid. Antimicrobial milk lipids and peptides can work synergistically to decrease both the concentrations of individual compounds required for protection and, as importantly, greatly reduce the time needed for pathogen inactivation. The more rapidly pathogens are inactivated the less likely they are to establish an infection. The total antimicrobial protection provided by human milk appears to be far more than can be elucidated by examining protective factors individually.

Development of a convenient ex vivo model for the study of the transcorneal permeation of drugs: histological and permeability evaluation.

PubMed

Pescina, Silvia; Govoni, Paolo; Potenza, Arianna; Padula, Cristina; Santi, Patrizia; Nicoli, Sara

2015-01-01

In this paper, an ex vivo model for the study of the transcorneal permeation of drugs, based on porcine tissues, was evaluated. The setup is characterized by ease of realization, absence of O₂ and CO₂ bubbling and low cost; additionally, the large availability of porcine tissue permits a high throughput. Histological images showed the comparability between porcine and human corneas and confirmed the effectiveness of the isolation procedure. A new de-epithelization procedure based on a thermal approach was also set up to simulate cornea permeability in pathological conditions. The procedure did not affect the integrity of the underlying layers and allowed the characterization of the barrier properties of epithelium and stroma. Six compounds with different physicochemical properties were tested: fluorescein, atenolol, propranolol, diclofenac, ganciclovir and lidocaine. The model highlighted the barrier function played by epithelium toward the diffusion of hydrophilic compounds and the permselectivity with regard to more lipophilic molecules. In particular, positively charged compounds showed a significantly higher transcorneal permeability than negatively charged compounds. The comparability of results with literature data supports the goodness and the robustness of the model, especially taking into account the behavior of fluorescein, which is generally considered a marker of tissue integrity. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Noninvasive Vascular Displacement Estimation for Relative Elastic Modulus Reconstruction in Transversal Imaging Planes

PubMed Central

Hansen, Hendrik H.G.; Richards, Michael S.; Doyley, Marvin M.; de Korte, Chris L.

2013-01-01

Atherosclerotic plaque rupture can initiate stroke or myocardial infarction. Lipid-rich plaques with thin fibrous caps have a higher risk to rupture than fibrotic plaques. Elastic moduli differ for lipid-rich and fibrous tissue and can be reconstructed using tissue displacements estimated from intravascular ultrasound radiofrequency (RF) data acquisitions. This study investigated if modulus reconstruction is possible for noninvasive RF acquisitions of vessels in transverse imaging planes using an iterative 2D cross-correlation based displacement estimation algorithm. Furthermore, since it is known that displacements can be improved by compounding of displacements estimated at various beam steering angles, we compared the performance of the modulus reconstruction with and without compounding. For the comparison, simulated and experimental RF data were generated of various vessel-mimicking phantoms. Reconstruction errors were less than 10%, which seems adequate for distinguishing lipid-rich from fibrous tissue. Compounding outperformed single-angle reconstruction: the interquartile range of the reconstructed moduli for the various homogeneous phantom layers was approximately two times smaller. Additionally, the estimated lateral displacements were a factor of 2–3 better matched to the displacements corresponding to the reconstructed modulus distribution. Thus, noninvasive elastic modulus reconstruction is possible for transverse vessel cross sections using this cross-correlation method and is more accurate with compounding. PMID:23478602

Synthesis and biological evaluation of new BSH-conjugated chlorin derivatives as agents for both photodynamic therapy and boron neutron capture therapy of cancer.

PubMed

Asano, Ryuji; Nagami, Amon; Fukumoto, Yuki; Miura, Kaori; Yazama, Futoshi; Ito, Hideyuki; Sakata, Isao; Tai, Akihiro

2014-11-01

New disodium mercaptoundecahydro-closo-dodecaborate (BSH)-conjugated chlorin derivatives 11, 12, 16 and 20 as agents for both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer were synthesized. The in vivo biodistribution and clearance of 11, 12, 16 and 20 were investigated in tumor-bearing mice. Compounds 12 and 16 showed good tumor-selective accumulation among the four derivatives. The time to maximum accumulation of compound 16 in tumor tissue was one-fourth of that of compound 12, and clearance from normal tissues of compound 16 was similar to that of compound 12. The in vivo therapeutic efficacy of PDT using 16, which has twice as many boron atoms as 12, was evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light-emitting diode irradiation at 6h after injection of 16. Tumor growth was significantly inhibited by PDT using 16. These results suggested that 16 is a good candidate for both PDT and BNCT of cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

Inhibitory Effect of Methyl 2-(4'-Methoxy-4'-oxobutanamide) Benzoate from Jerusalem Artichoke (Helianthus tuberosus) on the Inflammatory Paracrine Loop between Macrophages and Adipocytes.

PubMed

Jung, Yun Joo; Kim, Byung Oh; Kwak, Jong Hwan; Pyo, Suhkneung

2016-12-14

The interaction between macrophages and adipocytes is known to aggravate inflammation of the adipose tissue, leading to decreased insulin sensitivity. Hence, attenuation of the inflammatory paracrine loop between macrophages and adipocytes is deemed essential to ameliorate insulin resistance and diabetes mellitus type 2. Methyl 2-(4'-methoxy-4'-oxobutanamide) benzoate (compound 1), a newly isolated compound from Jerusalem srtichoke (JA), has not been biologically characterized yet. Here, we investigated whether JA-derived compound 1 attenuates the inflammatory cycle between RAW 264.7 macrophages and 3T3-L1 adipocytes. Compound 1 suppressed the inflammatory response of RAW 264.7 cells to lipopolysaccharide through decreased secretion of IL-1β, IL-6, and TNF-α. Moreover, the mRNA expression of TNF-α, IL-6, IL-1β, MCP-1, and Rantes and MAPK pathway activation in 3T3-L1 adipocytes, incubated in macrophage-conditioned media, were inhibited. These findings suggest an anti-inflammatory effect of a newly extracted compound against adipose tissue inflammation and insulin resistance.

Organochlorine pesticides and PCBs in human adipose tissues in Poland

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ludwicki, J.K.; Goralczyk, K.

1994-03-01

Most of the persistent organochlorine (OC) pesticides, excluding lindane, were banned in Poland in 1975/76. The first restrictions concerning the use and marketing of lindane (gamma-HCH) became effective in 1980 and were gradually extended until it's agricultural use was ultimately banned in 1989. Unfortunately, there are no detailed data on the use and release of PCBs to the environment in Poland. The former studies showed that in the late seventies the concentrations of OC pesticides and their metabolites in men reached considerable high levels. Despite of the restrictions or bans of these pesticides in most of the countries of themore » temperate climate, they still circulate in various food chains and eventually concentrate in man. Many authors claim an uneven distribution of the OC compounds in the population and report different levels in men and women and also some relations between OC compounds levels in fat tissues and age. Environmental contamination also plays an important role in the magnitude of OC compounds levels in man. The aim of this paper is to present the actual concentrations of HCB, p,p[prime]-DDT, p,p[prime]-DDE, isomers of HCH (alpha, beta, gamma), and PCBs in human adipose tissues particularly regarding age and sex as possible factors influencing the levels of these compounds and to contribute to the general discussion on the distribution patterns of the organochlorine compounds in the population. 12 refs., 3 tabs.« less

Radioprotection of mouse skin vasculature and the RIF-1 fibrosarcoma by WR-2721

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penhaligon, M.

1984-09-01

The degree of radioprotection obtained with WR-2721 is critically dependent upon the oxygen tension of the tissue concerned. It was therefore considered of interest to examine the response of vascular tissue, which would be supposedly well oxygenated, to treatment with WR-2721 plus X rays. The response of this tissue is of interest because of its role in late radiation damage. In addition, for therapeutic gain an agent must protect normal tissue without concomitant tumor protection. However, data on tumor radioprotection have been conflicting and therefore the effect of WR-2721 on an experimental tumor was also tested. Vascular damage was assessedmore » using the fact that tumors grow more slowly in irradiated beds (Tumor Bed Effect). WR-2721 injected 30 minutes before 5 to 30 Gy X rays protected skin stroma by a factor of 1.6. However, WR-2721 given 10 to 60 minutes before 20 Gy X rays to the RIF-1 tumor had either no effect or was protective, according to the method of immobilizing the mice during irradiation.« less

Design and evaluation of safety operation VR training system for robotic catheter surgery.

PubMed

Wang, Yu; Guo, Shuxiang; Li, Yaxin; Tamiya, Takashi; Song, Yu

2018-01-01

A number of remote robotic catheter systems have been developed to protect physicians from X-ray exposure in endovascular surgery. However, the teleoperation prevents the physicians sensing the force directly which may easily result in healthy vessels injured. To realize the safe operation, a tissue protection-based VR training system has been developed in this paper to prevent collateral damage by collision. The integrated VR simulator cannot only remind the novice possible collisions by visual signs, but also cooperate with the newly designed tissue protection mechanism to remit collision trauma beforehand. Such mechanism exploits the diameter variable pulley in order to implement the safe interaction between catheter and vasculature. To testify the effectiveness of the tissue protection in training system, we invited four non-medical students to participate the successive 5 days training session. The evaluation results show that the average impingement distance (representing tissue damage) to vascular wall has been reduced to 0.6 mm, and the collision frequency is greatly decreased which implies the realization of relative safe catheterization.

The gnotobiotic brine shrimp (Artemia franciscana) model system reveals that the phenolic compound pyrogallol protects against infection through its prooxidant activity.

PubMed

Baruah, Kartik; Duy Phong, Ho Phuong Pham; Norouzitallab, Parisa; Defoirdt, Tom; Bossier, Peter

2015-12-01

The phenolic compound pyrogallol is the functional unit of many polyphenols and currently there has been a growing interest in using this compound in human and animal health owing to its health-promoting effects. The biological actions of pyrogallol moiety (and polyphenols) in inducing health benefitting effects have been studied; however, the mechanisms of action remain unclear yet. Here, we aimed at unravelling the underlying mechanism of action behind the protective effects of pyrogallol against bacterial infection by using the gnotobiotically-cultured brine shrimp Artemia franciscana and pathogenic bacteria Vibrio harveyi as host-pathogen model system. The gnotobiotic test system represents an exceptional system for carrying out such studies because it eliminates any possible interference of microbial communities (naturally present in the experimental system) in mechanistic studies and furthermore facilitates the interpretation of the results in terms of a cause effect relationship. We provided clear evidences suggesting that pyrogallol pretreament, at an optimum concentration, induced protective effects in the brine shrimp against V. harveyi infection. By pretreating brine shrimp with pyrogallol in the presence or absence of an antioxidant enzyme mixture (catalase and superoxide dismutase), we showed that the Vibrio-protective effect of the compound was caused by its prooxidant action (e.g. generation of hydrogen peroxide, H2O2). We showed further that generation of prooxidant is linked to the induction of heat shock protein Hsp70, which is involved in eliciting the prophenoloxidase and transglutaminase immune responses. The ability of pyrogallol to induce protective immunity makes it a potential natural protective agent that might be a potential preventive modality for different host-pathogen systems. Copyright © 2015 Elsevier Inc. All rights reserved.

Improved normal tissue protection by proton and X-ray microchannels compared to homogeneous field irradiation.

PubMed

Girst, S; Marx, C; Bräuer-Krisch, E; Bravin, A; Bartzsch, S; Oelfke, U; Greubel, C; Reindl, J; Siebenwirth, C; Zlobinskaya, O; Multhoff, G; Dollinger, G; Schmid, T E; Wilkens, J J

2015-09-01

The risk of developing normal tissue injuries often limits the radiation dose that can be applied to the tumour in radiation therapy. Microbeam Radiation Therapy (MRT), a spatially fractionated photon radiotherapy is currently tested at the European Synchrotron Radiation Facility (ESRF) to improve normal tissue protection. MRT utilizes an array of microscopically thin and nearly parallel X-ray beams that are generated by a synchrotron. At the ion microprobe SNAKE in Munich focused proton microbeams ("proton microchannels") are studied to improve normal tissue protection. Here, we comparatively investigate microbeam/microchannel irradiations with sub-millimetre X-ray versus proton beams to minimize the risk of normal tissue damage in a human skin model, in vitro. Skin tissues were irradiated with a mean dose of 2 Gy over the irradiated area either with parallel synchrotron-generated X-ray beams at the ESRF or with 20 MeV protons at SNAKE using four different irradiation modes: homogeneous field, parallel lines and microchannel applications using two different channel sizes. Normal tissue viability as determined in an MTT test was significantly higher after proton or X-ray microchannel irradiation compared to a homogeneous field irradiation. In line with these findings genetic damage, as determined by the measurement of micronuclei in keratinocytes, was significantly reduced after proton or X-ray microchannel compared to a homogeneous field irradiation. Our data show that skin irradiation using either X-ray or proton microchannels maintain a higher cell viability and DNA integrity compared to a homogeneous irradiation, and thus might improve normal tissue protection after radiation therapy. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Britanin Ameliorates Cerebral Ischemia-Reperfusion Injury by Inducing the Nrf2 Protective Pathway.

PubMed

Wu, Guozhen; Zhu, Lili; Yuan, Xing; Chen, Hao; Xiong, Rui; Zhang, Shoude; Cheng, Hao; Shen, Yunheng; An, Huazhang; Li, Tiejun; Li, Honglin; Zhang, Weidong

2017-10-10

Oxidative stress is considered the major cause of tissue injury after cerebral ischemia. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is one of the most important defensive mechanisms against oxidative stresses and has been confirmed as a target for stroke treatment. Thus, we desired to find new Nrf2 activators and test their neuronal protective activity both in vivo and in vitro. The herb-derived compound, Britanin, is a potent inducer of the Nrf2 system. Britanin can induce the expression of protective enzymes and reverse oxygen-glucose deprivation, followed by reperfusion (OGD-R)-induced neuronal injury in primary cortical neurons in vitro. Furthermore, the administration of Britanin significantly ameliorated middle cerebral artery occlusion-reperfusion (MCAO-R) insult in vivo. We report here the crystal structure of the complex of Britanin and the BTB domain of Keap1. Britanin selectively binds to a conserved cysteine residue, cysteine 151, of Keap1 and inhibits Keap1-mediated ubiquitination of Nrf2, leading to induction of the Nrf2 pathway. Britanin is a potent inducer of Nrf2. The complex crystal structure of Britanin and the BTB domain of Keap1 help clarify the mechanism of Nrf2 induction. Britanin was proven to protect primary cortical neurons against OGD-R-induced injury in an Nrf2-dependant way. Additionally, Britanin had excellent cerebroprotective effect in an MCAO-R model. Our results demonstrate that the natural product Britanin with potent Nrf2-activating and neural protective activities both in vitro and in vivo could be developed into a cerebroprotective therapeutic agent. Antioxid. Redox Signal. 27, 754-768.

Interaction of Human Enteric Viruses with Microbial Compounds: Implication for Virus Persistence and Disinfection Treatments.

PubMed

Waldman, Prunelle; Meseguer, Alba; Lucas, Françoise; Moulin, Laurent; Wurtzer, Sébastien

2017-12-05

Although the interaction between phages and bacteria has already been well described, it only recently emerged that human viruses also interact with bacteria in the mammalian gut. We studied whether this interaction could occur in tap water and thus confer enteric viruses protection against temperature and the classical disinfection treatments used in drinking water production. We demonstrated that the addition of lipopolysaccharide or peptidoglycan of bacterial origin to enterovirus provides thermal protection through stabilization of the viral capsid. This interaction plays a role when viruses are exposed to disinfection that targets the capsid, but less so when the virus genome is directly targeted. The interaction seems to be serotype-specific, suggesting that the capsid protein sequence could be important. The protection is linked to a direct association between viral particles and bacterial compounds as observed by microscopy. These results show that bacterial compounds present in the environment can affect virus inactivation.

Food processing strategies to enhance phenolic compounds bioaccessibility and bioavailability in plant-based foods.

PubMed

Ribas-Agustí, Albert; Martín-Belloso, Olga; Soliva-Fortuny, Robert; Elez-Martínez, Pedro

2017-06-13

Phenolic compounds are important constituents of plant-based foods, as their presence is related to protective effects on health. To exert their biological activity, phenolic compounds must be released from the matrix during digestion in an absorbable form (bioaccessible) and finally absorbed and transferred to the bloodstream (bioavailable). Chemical structure and matrix interactions are some food-related factors that hamper phenolic compounds bioaccessibility and bioavailability, and that can be counteracted by food processing. It has been shown that food processing can induce chemical or physical modifications in food that enhance phenolic compounds bioaccessibility and bioavailability. These changes include: (i) chemical modifications into more bioaccessible and bioavailable forms; (ii) cleavage of covalent or hydrogen bonds or hydrophobic forces that attach phenolic compounds to matrix macromolecules; (iii) damaging microstructural barriers such as cell walls that impede the release from the matrix; and (iv) create microstructures that protect phenolic compounds until they are absorbed. Indeed, food processing can produce degradation of phenolic compounds, however, it is possible to counteract it by modulating the operating conditions in favor of increased bioaccessibility and bioavailability. This review compiles the current knowledge on the effects of processing on phenolic compounds bioaccessibility or bioavailability, while suggesting new guidelines in the search of optimal processing conditions as a step forward towards the design of healthier foods.

40 CFR 62.10627 - Identification of sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.10627 Section 62.10627 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Metals, Acid Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Municipal Waste...

40 CFR 62.3651 - Identification of sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.3651 Section 62.3651 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS..., Acid Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Municipal Waste Combustors...

40 CFR 62.5111 - Identification of sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.5111 Section 62.5111 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS..., Acid Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Municipal Waste Combustors...

40 CFR 62.10150 - Identification of sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.10150 Section 62.10150 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Metals, Acid Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Municipal Waste...

40 CFR 62.9150 - Identification of sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.9150 Section 62.9150 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS..., Acid Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Municipal Waste Combustors...

40 CFR 62.9641 - Identification of sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.9641 Section 62.9641 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Metals, Acid Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Municipal Waste...

40 CFR 62.2355 - Identification of sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.2355 Section 62.2355 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS..., Acid Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Municipal Waste Combustors...

40 CFR 62.3341 - Identification of sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.3341 Section 62.3341 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS..., Acid Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Hospital / Medical Infectious...

40 CFR 62.2606 - Identification of sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.2606 Section 62.2606 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS..., Acid Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Municipal Waste Combustors...

40 CFR 62.3641 - Identification of sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.3641 Section 62.3641 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS..., Acid Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Hospital/medical Infectious...

40 CFR 62.4975 - Identification of sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.4975 Section 62.4975 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS..., Acid Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Municipal Waste Combustors...

40 CFR 62.104 - Identification of sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.104 Section 62.104 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS..., Acid Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Municipal Waste Combustors...

40 CFR 62.9505 - Identification of sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.9505 Section 62.9505 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS..., Acid Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Municipal Waste Combustors...

40 CFR 62.3110 - Identification of plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of plan. 62.3110 Section 62.3110 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED..., Organic Compounds, Particulates and Nitrogen Oxide Emissions from Existing Hospital/medical/infectious...

40 CFR 62.11870 - Identification of sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.11870 Section 62.11870 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Metals, Acid Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Municipal Waste...

40 CFR 62.5425 - Identification of sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.5425 Section 62.5425 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Metals, Acid Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Municipal Waste...

40 CFR 62.9140 - Identification of source.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of source. 62.9140 Section 62.9140 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS...] Metals, Acid Gases, Organic Compounds and Nitrogen Oxide Emissions From Existing Municipal Waste...

40 CFR 62.9642 - Effective dates.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Effective dates. 62.9642 Section 62.9642 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Municipal Waste Combustors with A...

Radioiodinated branched carbohydrates

DOEpatents

Goodman, Mark M.; Knapp, Jr., Furn F.

1989-01-01

A radioiodinated branched carbohydrate for tissue imaging. Iodine-123 is stabilized in the compound by attaching it to a vinyl functional group that is on the carbohydrate. The compound exhibits good uptake and retention and is promising in the development of radiopharmaceuticals for brain, heart and tumor imaging.

[Distribution laws of 5 compounds in rhizome and root of Polygonum cuspidate].

PubMed

Liu, Yao-wut; Wang, Jun; Chu, Shan-shan; Cheng, Ming-en; Fang, Cheng-wu

2015-12-01

To understand the distribution and accumulation rules of polydatin, resveratrol, anthraglycoside B, emodin and physicion in different tissue structure of rhizome and root of Polygonum cospidatum, the content of 5 active compounds were analyzed simultaneously by HPLC, based on plant anatomy and histochemistry. The rhizome and root consist of different tissues, with an increased diameter, the proportions of the secondary xylem and phloem have increased. Resveratrol and polydatin mainly distributed in the pith, the secondary phloem and periderm of rhizome, and the secondary phloem and periderm of the root, while emodin and anthraglycoside B concentrated in the secondary structure and pith of rhizome mostly. In different thickness of the measured samples, the total contents of 5 compounds were correspondingly higher in thinner rhizome and root than those in the coarse ones.

The Lymphatic Response to Injury with Soft-Tissue Reconstruction in High-Energy Open Tibial Fractures of the Lower Extremity.

PubMed

van Zanten, Malou C; Mistry, Raakhi M; Suami, Hiroo; Campbell-Lloyd, Andrew; Finkemeyer, James P; Piller, Neil B; Caplash, Yugesh

2017-02-01

Severe compound tibial fractures are associated with extensive soft-tissue damage, resulting in disruption of lymphatic pathways that leave the patient at risk of developing chronic lymphedema. There are limited data on lymphatic response following lower limb trauma. Indocyanine green fluorescence lymphography is a novel, real-time imaging technique for superficial lymphatic mapping. The authors used this technique to image the superficial lymphatic vessels of the lower limbs in patients with severe compound tibial fracture. Baseline demographics and clinical and operative details were recorded in a prospective cohort of 17 patients who had undergone bone and soft-tissue reconstruction after severe compound tibial fracture between 2009 and 2014. Normal lymphatic images were obtained from the patients' noninjured limbs as a control. In this way, the authors investigated any changes to the normal anatomy of the lymphatic system in the affected limbs. Of the 17 patients, eight had free muscle flaps with split-thickness skin grafting, one had a free fasciocutaneous flap, one had a full-thickness skin graft, six had local fasciocutaneous flaps, and one had a pedicled gastrocnemius flap. None of the free flaps demonstrated any functional lymphatic vessels; the fasciocutaneous flaps and the skin graft demonstrated impaired lymphatic vessel function and dermal backflow pattern similar to that in lymphedema. Local flaps demonstrated lymphatic blockage at the scar edge. Severe compound fractures and the associated soft-tissue injury can result in significant lymphatic disruption and an increased risk for the development of chronic lymphedema.

Melatonin and hydroxytyrosol protect against oxidative stress related to the central nervous system after the ingestion of three types of wine by healthy volunteers.

PubMed

Marhuenda, Javier; Medina, Sonia; Martínez-Hernández, Pedro; Arina, Simón; Zafrilla, Pilar; Mulero, Juana; Oger, Camille; Galano, Jean-Marie; Durand, Thierry; Ferreres, Federico; Gil-Izquierdo, Angel

2017-01-25

Adrenic acid (AdA) and docosahexaenoic acid (DHA) peroxidation produces F 2 -dihomo-IsoPs and neuroprostanes, which have been related to oxidative damage in the central nervous system. Besides polyphenols, melatonin (MEL) and hydroxytyrosol (OHTyr) could be partly responsible for the antioxidant benefits of red wine (excluding colon derivatives). In order to elucidate whether these compounds are responsible for the protective antioxidant effects of red wine, a double-blind, crossover, placebo-controlled in vivo study - involving the intake of red wines and their native musts by healthy volunteers - was performed. The urinary metabolites decreased after the administration of red wines, to a greater extent than after the intake of their corresponding musts or ethanol. Melatonin is the most effective compound that protects adrenic acid from oxidative attack, judged by the reduction in the formation of F 2 -dihomo-isoprostanes. Similarly, hydroxytyrosol, being the most effective bioactive compound in reducing the formation of F 3 -neuroprostanes n-6 DPA and F 4 -neuroprostanes, protected docosahexaenoic and eicosapentaenoic acids from oxidative attack.

Mineral protection of soil carbon counteracted by root exudates [Root exudates counteract mineral control on soil carbon turnover

DOE PAGES

Keiluweit, Marco; Bougoure, Jeremy J.; Nico, Peter S.; ...

2015-03-30

Multiple lines of existing evidence suggest that climate change enhances root exudation of organic compounds into soils. Recent experimental studies show that increased exudate inputs may cause a net loss of soil carbon. This stimulation of microbial carbon mineralization (‘priming’) is commonly rationalized by the assumption that exudates provide a readily bioavailable supply of energy for the decomposition of native soil carbon (co-metabolism). Here we show that an alternate mechanism can cause carbon loss of equal or greater magnitude. We find that a common root exudate, oxalic acid, promotes carbon loss by liberating organic compounds from protective associations with minerals.more » By enhancing microbial access to previously mineral-protected compounds, this indirect mechanism accelerated carbon loss more than simply increasing the supply of energetically more favourable substrates. Lastly, our results provide insights into the coupled biotic–abiotic mechanisms underlying the ‘priming’ phenomenon and challenge the assumption that mineral-associated carbon is protected from microbial cycling over millennial timescales.« less

TISSUE HYPOXIA AS A MECHANISM OF THE ANTI-RADIO PROTECTION EFFECT OF ADRENALIN, HEROIN AND MORPHINE (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konstantinova, M.M.; Graevskii, E.J.

1960-07-21

The protective mechanism of adrenalin heroin, and - morphine on white mice 12 to 18 weeks old, and weighing 18 to 23 g was analyzed in order to determine the protection action of neurotropical substances in relation to their ability to reduce oxygen in tissues. Parallel studies were made of the time factor influence. The results indicate that the investigated substances are capable of reducing the level of oxygen in tissue, and particularly in the spleen. The reduction and restoration of the oxygen content correspond in general to the reduction and increase of mortality. Data confirm that the protective effectsmore » of adrenalin, heroin, and morphine are the result of their ability to produce hypoxia in radiosensitive organs. The hypoxia is induced by the adrenalin pressure effect and by morphine and heroin depression of respiratory centers. (R.V.J.)« less

OPC-compounds prevent oxidant-induced carbonylation and depolymerization of the F-actin cytoskeleton and intestinal barrier hyperpermeability.

PubMed

Banan, A; Fitzpatrick, L; Zhang, Y; Keshavarzian, A

2001-02-01

Rebamipide (OPC-12759), a quinolone derivative, and OPC-6535, a thiazol-carboxylic acid derivative, are compounds with ability to protect gastrointestinal (GI) mucosal integrity against reactive oxygen metabolites (ROM). The underlying mechanism of OPC-mediated protection remains poorly understood. It is now established that ROM can injure the mucosa by disruption of the cytoskeletal network, a key component of mucosal barrier integrity. We, therefore, investigated whether OPC compounds prevent the oxidation, disassembly, and instability of the cytoskeletal protein actin and, in turn, protect intestinal barrier function against ROM. Human intestinal (Caco-2) cell monolayers were pretreated with OPC (-12759 or -6535) prior to incubation with ROM (H2O2) or HOCl). Effects on cell integrity (ethidium homodimer-1), epithelial barrier function (fluorescein sulfonic acid clearance), and actin cytoskeletal integrity (high-resolution laser confocal) were then determined. Cells were also processed for quantitative immunoblotting of G- and F-actin to measure oxidation (carbonylation) and disassembly of actin. In monolayers exposed to ROM, preincubation with OPC compounds prevented actin oxidation, decreased depolymerized G-actin, and enhanced the stable F-actin. Concomitantly, OPC agents abolished both actin cytoskeletal disruption and monolayer barrier dysfunction. Data suggest for the first time that OPC drugs prevent oxidation of actin and lead to the protection of actin cytoskeleton and intestinal barrier integrity against oxidant insult. Accordingly, these compounds may be used as novel therapeutic agents for the treatment of a variety of oxidative inflammatory intestinal disorders with an abnormal mucosal barrier such as inflammatory bowel disease.

Use of Shark Dental Protein to Estimate Trophic Position via Amino Acid Compound-Specific Isotope Analysis

NASA Astrophysics Data System (ADS)

Hayes, M.; Herbert, G.; Ellis, G.

2017-12-01

The diets of apex predators such as sharks are expected to change in response to overfishing of their mesopredator prey, but pre-anthropogenic baselines necessary to test for such changes are lacking. Stable isotope analysis (SIA) of soft tissues is commonly used to study diets in animals based on the bioaccumulation of heavier isotopes of carbon and nitrogen with increasing trophic level. In specimens representing pre-anthropogenic baselines, however, a modified SIA approach is needed to deal with taphonomic challenges, such as loss of soft tissues or selective loss of less stable amino acids (AAs) in other sources of organic compounds (e.g., teeth or bone) which can alter bulk isotope values. These challenges can be overcome with a compound-specific isotope analysis of individual AAs (AA-CSIA), but this first requires a thorough understanding of trophic enrichment factors for individual AAs within biomineralized tissues. In this study, we compare dental and muscle proteins of individual sharks via AA-CSIA to determine how trophic position is recorded within teeth and whether that information differs from that obtained from soft tissues. If skeletal organics reliably record information about shark ecology, then archaeological and perhaps paleontological specimens can be used to investigate pre-anthropogenic ecosystems. Preliminary experiments show that the commonly used glutamic acid/phenylalanine AA pairing may not be useful for establishing trophic position from dental proteins, but that estimated trophic position determined from alternate AA pairs are comparable to those from muscle tissue within the same species.

Partition of environmental chemicals between maternal and fetal blood and tissues.

PubMed

Needham, Larry L; Grandjean, Philippe; Heinzow, Birger; Jørgensen, Poul J; Nielsen, Flemming; Patterson, Donald G; Sjödin, Andreas; Turner, Wayman E; Weihe, Pal

2011-02-01

Passage of environmental chemicals across the placenta has important toxicological consequences, as well as for choosing samples for analysis and for interpreting the results. To obtain systematic data, we collected in 2000 maternal and cord blood, cord tissue, placenta, and milk in connection with births in the Faroe Islands, where exposures to marine contaminants is increased. In 15 sample sets, we measured a total of 87 environmental chemicals, almost all of which were detected both in maternal and fetal tissues. The maternal serum lipid-based concentrations of organohalogen compounds averaged 1.7 times those of cord serum, 2.8 times those of cord tissue and placenta, and 0.7 those of milk. For organohalogen compounds detectable in all matrices, a high degree of correlation between concentrations in maternal serum and the other tissues investigated was generally observed (r(2) > 0.5). Greater degree of chlorination resulted in lower transfer from maternal serum into milk. Concentrations of pentachlorbenzene, γ-hexachlorocyclohexane, and several polychlorinated biphenyl congeners with low chlorination were higher in fetal samples and showed poor correlation with maternal levels. Perfluorinated compounds occurred in lower concentrations in cord serum than in maternal serum. Cadmium, lead, mercury, and selenium were all detected in fetal samples, but only mercury showed close correlations among concentrations in different matrices. Although the environmental chemicals examined pass through the placenta and are excreted into milk, partitions between maternal and fetal samples are not uniform.

The quest for bacterial allergens.

PubMed

Nordengrün, Maria; Michalik, Stephan; Völker, Uwe; Bröker, Barbara M; Gómez-Gascón, Lidia

2018-04-26

Allergies are complex diseases featuring local tissue inflammation, which is characterized by an exaggerated type 2 immune response to environmental compounds known as allergens. Pollens, environmental fungi, and house dust mites are examples of common allergens. Bacteria have a dual role in allergy. Usually, they are associated with protection, however, certain bacterial species promote the development and exacerbation of allergic inflammation. Notably, IgE antibodies specific for bacterial antigens are found in the sera of allergic individuals. This implies that some bacterial factors are allergens, eliciting a specific type 2 immune response. However, to date, only a few of these are molecularly defined. This review summarizes the current knowledge about known bacterial allergens, and it provides an overview of the available techniques for the discovery of new allergens as well as for measuring the immune responses directed against them. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells.

PubMed

Debbabi, Meryam; Nury, Thomas; Zarrouk, Amira; Mekahli, Nadia; Bezine, Maryem; Sghaier, Randa; Grégoire, Stéphane; Martine, Lucy; Durand, Philippe; Camus, Emmanuelle; Vejux, Anne; Jabrane, Aymen; Bretillon, Lionel; Prost, Michel; Moreau, Thibault; Ammou, Sofien Ben; Hammami, Mohamed; Lizard, Gérard

2016-11-25

Lipid peroxidation products, such as 7-ketocholesterol (7KC), may be increased in the body fluids and tissues of patients with neurodegenerative diseases and trigger microglial dysfunction involved in neurodegeneration. It is therefore important to identify synthetic and natural molecules able to impair the toxic effects of 7KC. We determined the impact of 7KC on murine microglial BV-2 cells, especially its ability to trigger mitochondrial and peroxisomal dysfunction, and evaluated the protective effects of α- and γ-tocopherol, Trolox, and oleic acid (OA). Multiple complementary chemical assays, flow cytometric and biochemical methods were used to evaluate the antioxidant and cytoprotective properties of these molecules. According to various complementary assays to estimate antioxidant activity, only α-, and γ-tocopherol, and Trolox had antioxidant properties. However, only α-tocopherol, γ-tocopherol and OA were able to impair 7KC-induced loss of mitochondrial transmembrane potential, which is associated with increased permeability to propidium iodide, an indicator of cell death. In addition, α-and γ-tocopherol, and OA were able to prevent the decrease in Abcd3 protein levels, which allows the measurement of peroxisomal mass, and in mRNA levels of Abcd1 and Abcd2, which encode for two transporters involved in peroxisomal β-oxidation. Thus, 7KC-induced side effects are associated with mitochondrial and peroxisomal dysfunction which can be inversed by natural compounds, thus supporting the hypothesis that the composition of the diet can act on the function of organelles involved in neurodegenerative diseases.

Blood metabolism study on protection of residual renal function of hemodialysis patients by traditional Chinese medicine Kidney Flaccidity Compound.

PubMed

Hu, Qiong-Dan; Wu, Wei-Hua; Zeng, Yan; Wen, Ji; Li, Xiao-Jun; Pan, Wei; Zhang, Mao-Ping; Hu, Bo; Lei, Chun-Yan; Fan, Junming

2018-04-30

In recent years, metabolomics using high-performance liquid chromatography (UPLC) has been used to study the metabolic profiles in plasma, urine, stool and tissue in animal model of chronic kidney disease (CKD). In the previous work, we found that traditional Chinese medicine (TCM) "Kidney Flaccidity Compound" (KFC) based on "kidney flaccidity theory" can improve renal function and quality of life of patients with kidney disease. This study aimed to investigate the metabolic profiles in peripheral blood of hemodialysis patients administrated by KFC for 1.5 and 3 months and explore the potential metabolic mechanism using UPLC. Results showed that 121 metabolites were different between KFC 3-months group and untreated control, of which 75 were significantly upregulated and 46 were significantly downregulated. In the 1.5-months treatment group, there were 365 metabolites, of which 164 were significantly upregulated and 192 downregulated. There were 6 metabolites and 15 metabolites upregulated 3-fold in 3-months and 1.5-months KFC treatment group, respectively. In addition, more than 60 new metabolites were identified in the peripheral blood in KFC treated patients, including two potential diagnostic markers MGDG 30:8 and 2-(hydroxymethyl)-6-[[(1R,4S) -2,2,4-trimethyl-3-oxabicyclo[2.2.2]octan-5-yl]oxy]oxane-3,4,5-triol. The pathway enrichment analysis showed thce differential metabolites mainly enriched in Arginine and proline metabolism, Urea cycle, Tyrosine metabolism, Methionine metabolism, Tricarboxylic acid cycle, and Androgen and estrogen metabolism. The findings are helpful to reveal the mechanism of KFC protects CKD, and to provide a new strategy for recovery renal function in hemodialysis patients.

Effect of supplemented and topically applied antioxidant substances on human tissue.

PubMed

Darvin, M; Zastrow, L; Sterry, W; Lademann, J

2006-01-01

Systemic and topical application of antioxidant substances for the medical treatment and prophylaxis of many diseases as well as additional protection of the skin against the destructive action of free radicals and other reactive species has become very popular during the past years. Stimulated by the positive results of a fruit and vegetable diet in supporting medical treatment and in cosmetics, artificial and extracted antioxidant substances have been broadly applied. Surprisingly, not only positive but also strong negative results have been obtained by different authors. According to study reports artificial and extracted antioxidant substances support different kinds of medical therapies, if they are applied in mixtures of different compounds at low concentration levels. In the case of the application of high concentration of some single compounds, side effects were often observed. Regarding skin treatment by systemically applied antioxidant substances for cosmetic purposes, positive cosmetic effects as well as no effects, but almost no side effects, apart from a number of allergic reactions, were reported. One reason for this seems to be the lower concentration of systemically applied antioxidant substances in comparison with a medical application. Topical application of antioxidant substances is closely related to cosmetic treatment for skin protection and anti-aging. Positive results were also obtained in this case. The present review is an attempt to classify and summarize the published literature concerning the efficiency of action of systemic and topical applications of antioxidant substances, such as carotenoids and vitamins, on human organism and especially on the skin. The available literature on this topic is very extensive and the results are often contradictory. Nevertheless, there are some clear tendencies concerning systemic and topical application of antioxidant substances in medicine and cosmetics, and we summarize them in the present paper.

Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells

PubMed Central

Debbabi, Meryam; Nury, Thomas; Zarrouk, Amira; Mekahli, Nadia; Bezine, Maryem; Sghaier, Randa; Grégoire, Stéphane; Martine, Lucy; Durand, Philippe; Camus, Emmanuelle; Vejux, Anne; Jabrane, Aymen; Bretillon, Lionel; Prost, Michel; Moreau, Thibault; Ammou, Sofien Ben; Hammami, Mohamed; Lizard, Gérard

2016-01-01

Lipid peroxidation products, such as 7-ketocholesterol (7KC), may be increased in the body fluids and tissues of patients with neurodegenerative diseases and trigger microglial dysfunction involved in neurodegeneration. It is therefore important to identify synthetic and natural molecules able to impair the toxic effects of 7KC. We determined the impact of 7KC on murine microglial BV-2 cells, especially its ability to trigger mitochondrial and peroxisomal dysfunction, and evaluated the protective effects of α- and γ-tocopherol, Trolox, and oleic acid (OA). Multiple complementary chemical assays, flow cytometric and biochemical methods were used to evaluate the antioxidant and cytoprotective properties of these molecules. According to various complementary assays to estimate antioxidant activity, only α-, and γ-tocopherol, and Trolox had antioxidant properties. However, only α-tocopherol, γ-tocopherol and OA were able to impair 7KC-induced loss of mitochondrial transmembrane potential, which is associated with increased permeability to propidium iodide, an indicator of cell death. In addition, α-and γ-tocopherol, and OA were able to prevent the decrease in Abcd3 protein levels, which allows the measurement of peroxisomal mass, and in mRNA levels of Abcd1 and Abcd2, which encode for two transporters involved in peroxisomal β-oxidation. Thus, 7KC-induced side effects are associated with mitochondrial and peroxisomal dysfunction which can be inversed by natural compounds, thus supporting the hypothesis that the composition of the diet can act on the function of organelles involved in neurodegenerative diseases. PMID:27897980

Total antioxidant and oxidant status of plasma and renal tissue of cisplatin-induced nephrotoxic rats: protection by floral extracts of Calendula officinalis Linn.

PubMed

Verma, Pawan Kumar; Raina, Rajinder; Sultana, Mudasir; Singh, Maninder; Kumar, Pawan

2016-01-01

The present study was aimed to determine the total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) of plasma and renal tissue in cisplatin (cDDP) induced nephrotoxic rats and its protection by treatments with floral extracts of Calendula officinalis Linn. Treatment with cDDP elevated (p < 0.05) the levels of blood urea nitrogen, creatinine (CR), TOS, OSI and malondialdehyde (MDA) but lowered (p < 0.05) total plasma proteins, TAS, total thiols (TTH), blood glutathione (GSH) and antioxidant enzymes compared to the control group. Pre- and post-treatments of ethanolic floral extract of C. officinalis along with cDDP restored (p > 0.05) CR, albumin, TOS, GSH and activities of antioxidant enzymes in blood and renal tissue. Ethanolic extract treatments reduced (p < 0.05) MDA level in renal tissue without restoring the erythrocyte MDA level following cDDP treatment. These observations were further supported by the histopathological findings in renal tissue. Observations of the present study have shown that treatments with ethanolic floral extract of C. officinalis protect cDDP induced nephrotoxicity by restoring antioxidant system of the renal tissue.

Persistent Low-Level Replication of SIVΔnef Drives Maturation of Antibody and CD8 T Cell Responses to Induce Protective Immunity against Vaginal SIV Infection.

PubMed

Adnan, Sama; Reeves, R Keith; Gillis, Jacqueline; Wong, Fay E; Yu, Yi; Camp, Jeremy V; Li, Qingsheng; Connole, Michelle; Li, Yuan; Piatak, Michael; Lifson, Jeffrey D; Li, Wenjun; Keele, Brandon F; Kozlowski, Pamela A; Desrosiers, Ronald C; Haase, Ashley T; Johnson, R Paul

2016-12-01

Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef vaccination were protected, as defined by either apparent sterile protection or significant suppression of viremia in infected animals. Multiple parameters of CD8 T cell function temporally correlated with maturation of protection, including polyfunctionality, phenotypic differentiation, and redistribution to gut and lymphoid tissues. Importantly, we also demonstrate the induction of a tissue-resident memory population of SIV-specific CD8 T cells in the vaginal mucosa, which was dependent on ongoing low-level antigenic stimulation. Moreover, we show that vaginal and serum antibody titers inversely correlated with post-challenge peak viral load, and we correlate the accumulation and affinity maturation of the antibody response to the duration of the vaccination period as well as to the SIVΔnef antigenic load. In conclusion, maturation of SIVΔnef-induced CD8 T cell and antibody responses, both propelled by viral persistence in the gut mucosa and secondary lymphoid tissues, results in protective immune responses that are able to interrupt viral transmission at mucosal portals of entry as well as potential sites of viral dissemination.

Challenges of Translating Basic Research Into Therapeutics: Resveratrol as an Example

PubMed Central

Smoliga, James M.; Vang, Ole

2012-01-01

Basic science literature abounds with molecules that promise to ameliorate almost any disease, from curing cancer to slowing the aging process itself. However, most of these compounds will never even be evaluated in humans, let alone proven effective. Here, we use resveratrol as an example to highlight the enormous difficulties in understanding pharmacokinetics, determining side effects, and, ultimately, establishing mechanisms of action for a natural compound. Despite extensive interest and effort, and continuing promising results from basic science groups, very little is known even today about the effects of resveratrol in humans. Part of the problem is the unattractiveness of natural compounds to large, well-funded companies that could run clinical trials because developing their own molecules affords much greater protection for their intellectual property. In fact, selling unpatentable material motivates smaller nutraceutical companies to complicate the scientific problem even more—each creates its own proprietary blend, making it extremely difficult to compare their data with those of other companies, or of academic labs using pure compounds. But even beyond these problems lies a deeper one; resveratrol, and almost every natural compound, is likely to have many clinically relevant targets with different dose–response profiles, tissue distributions, and modifiers. Tackling this type of problem efficiently, and even beginning to address the spectrum of other molecules with claimed benefits, is likely to require the development of new paradigms and approaches. Examples include better molecular modeling to predict interactions, large-scale screens for toxic or other common effects, affinity-based methods to identify drug-interacting proteins, and better synthesis of existing data, including legislation to promote the release of trial results, and tracking of voluntary supplement usage. The evidence for benefits of resveratrol in humans remains too sparse to be conclusive; yet, the limited data that are available, combined with a growing list of animal studies, provide a strong justification for further study. PMID:21746739

40 CFR 59.207 - Test methods.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 6 2012-07-01 2012-07-01 false Test methods. 59.207 Section 59.207 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL... Compound Emission Standards for Consumer Products § 59.207 Test methods. Each manufacturer or importer...

40 CFR 59.207 - Test methods.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Test methods. 59.207 Section 59.207 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL... Compound Emission Standards for Consumer Products § 59.207 Test methods. Each manufacturer or importer...

40 CFR 59.207 - Test methods.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 6 2014-07-01 2014-07-01 false Test methods. 59.207 Section 59.207 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL... Compound Emission Standards for Consumer Products § 59.207 Test methods. Each manufacturer or importer...

40 CFR 59.207 - Test methods.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 5 2011-07-01 2011-07-01 false Test methods. 59.207 Section 59.207 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL... Compound Emission Standards for Consumer Products § 59.207 Test methods. Each manufacturer or importer...

40 CFR 59.207 - Test methods.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 6 2013-07-01 2013-07-01 false Test methods. 59.207 Section 59.207 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL... Compound Emission Standards for Consumer Products § 59.207 Test methods. Each manufacturer or importer...

40 CFR 62.9640 - Identification of plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of plan. 62.9640 Section 62.9640 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Municipal Waste Combustors with A...

40 CFR 62.3640 - Identification of plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of plan. 62.3640 Section 62.3640 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Hospital/medical Infectious Waste...

40 CFR 62.3340 - Identification of plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of plan. 62.3340 Section 62.3340 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... Gases, Organic Compounds and Nitrogen Oxide Emissions from Existing Hospital / Medical Infectious Waste...