Cytoprotective effect of palm kernel cake phenolics against aflatoxin B1-induced cell damage and its underlying mechanism of action.

PubMed

Oskoueian, Ehsan; Abdullah, Norhani; Zulkifli, Idrus; Ebrahimi, Mahdi; Karimi, Ehsan; Goh, Yong Meng; Oskoueian, Armin; Shakeri, Majid

2015-10-30

Palm kernel cake (PKC), a by-product of the palm oil industry is abundantly available in many tropical and subtropical countries. The product is known to contain high levels of phenolic compounds that may impede the deleterious effects of fungal mycotoxins. This study focused on the evaluation of PKC phenolics as a potential cytoprotective agent towards aflatoxin B1 (AFB1)-induced cell damage. The phenolic compounds of PKC were obtained by solvent extraction and the product rich in phenolic compounds was labeled as phenolic-enriched fraction (PEF). This fraction was evaluated for its phenolic compounds composition. The antioxidant activity of PEF was determined by using 1,1-diphenyl-2-picryl-hydrazil scavenging activity, ferric reducing antioxidant power, inhibition of ß-carotene bleaching, and thiobarbituric acid reactive substances assays. The cytotoxicity assay and molecular biomarkers analyses were performed to evaluate the cytoprotective effects of PEF towards aflatoxin B1 (AFB1)-induced cell damage. The results showed that PEF contained gallic acid, pyrogallol, vanillic acid, caffeic acid, syringic acid, epicatechin, catechin and ferulic acid. The PEF exhibited free radical scavenging activity, ferric reducing antioxidant power, ß-carotene bleaching inhibition and thiobarbituric acid reactive substances inhibition. The PEF demonstrated cytoprotective effects in AFB1-treated chicken hepatocytes by reducing the cellular lipid peroxidation and enhancing antioxidant enzymes production. The viability of AFB1-treated hepatocytes was improved by PEF through up-regulation of oxidative stress tolerance genes and down-regulation of pro-inflammatory and apoptosis associated genes. The present findings supported the proposition that the phenolic compounds present in PKC could be a potential cytoprotective agent towards AFB1 cytotoxicity.

Cytoprotective effect of Valeriana officinalis extract on an in vitro experimental model of Parkinson disease.

PubMed

de Oliveria, Diêgo Madureira; Barreto, George; De Andrade, Deyse Valverde G; Saraceno, Ezequiel; Aon-Bertolino, Laura; Capani, Francisco; Dos Santos El Bachá, Ramon; Giraldez, Lisandro Diego

2009-02-01

Parkinson's disease (PD) is one of the most important neurodegenerative worldwide disorders. The potential cytoprotective effects of aqueous extract of Valeriana officinalis on rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells were demonstrated. The cytotoxicity, cell viability and analysis of cellular morphology were performed by MTT-tetrazole (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and phase contrast microscopy, respectively. Significant changes in the cellular morphology, and condensation of the cell body could be observed when cells were treated with 300 nM rotenone for 48 h. Three different concentrations of Valeriana officinalis extract were used (0.049, 0.098 and 0.195 mg/mL). These extracts brought about an increase of 7.0 +/- 1.3%, 14.5 +/- 1.3% and 14.5 +/- 3.2% in cell viability. Our results indicated that neuroprotector action of the Valeriana officinalis extract provides support for later studies as they help understanding this drug for the development of cytoprotective various therapies in PD.

Effects of ethanol and arachidonic acid pathway inhibitors on the effectiveness of gastric mucosa cytoprotection.

PubMed

Lutnicki, K; Szpringer, E; Czerny, K; Ledwozyw, A

2001-01-01

Cytoprotection in the stomach, consisting in the mucus secretion, mucous circulation intensification and bicarbonate secretion to the gastric lumen, is highly dependent on the products of arachidonic acid pathway and peroxidative-antioxidative balance. The aim of the paper was to examine the effects of selected inhibitors of arachidonic acid pathway on the natural protective system of the gastric mucosa exposed to 50% ethanol. The results show that leukotrienes, thromboxane and oxygen reactive forms significantly impair the protective function of the gastric mucosa while prostaglandins and antioxidant enzymes act protectively.

Antioxidant and Cytoprotective Activities of Enzymatic Extracts from Rhizoid of Laminaria japonica

PubMed Central

Je, Jae-Young; Park, Soo Yeon; Ahn, Chang-Bum

2017-01-01

Rhizoid of Laminaria japonica was hydrolyzed with proteases and carbohydrases to obtain antioxidant materials. Oxygen radical absorbance capacity (ORAC) of the enzymatic extracts was evaluated and the Protamex extract (PE) exhibited the highest ORAC value. PE also potently scavenged 2,2-diphenyl-1-picrylhydrazyl radical, 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic) acid cation radical, and hydrogen peroxide (H2O2) and had good reducing power. PE inhibited hydroxyl radical-induced DNA scission by measuring the conversion of supercoiled pBR322 plasmid DNA to the open circular form. The cytoprotective effect of PE against H2O2-induced hepatic cell damage was also investigated. PE showed a dose-dependent cytoprotective effect in cultured hepatocytes by inhibiting intracellular reactive oxygen species scavenging activity. In addition, PE up-regulated the expression of heme oxygenase-1, which is a cytoprotective enzyme, by activating translocation of nuclear factor-erythroid 2-related factor 2. Taken together, the enzymatic extract of rhizoid of L. japonica, particularly PE, may be useful for antioxidant additives. PMID:29333384

Bioactive Flavonoids, Antioxidant Behaviour, and Cytoprotective Effects of Dried Grapefruit Peels (Citrus paradisi Macf.)

PubMed Central

Castro-Vazquez, Lucia; Alañón, María Elena; Rodríguez-Robledo, Virginia; Pérez-Coello, María Soledad; Hermosín-Gutierrez, Isidro; Díaz-Maroto, María Consuelo; Jordán, Joaquín; Galindo, María Francisca; Arroyo-Jiménez, María del Mar

2016-01-01

Grapefruit (Citrus paradisi Macf.) is an important cultivar of the Citrus genus which contains a number of nutrients beneficial to human health. The objective of the present study was to evaluate changes in bioactive flavonoids, antioxidant behaviour, and in vitro cytoprotective effect of processed white and pink peels after oven-drying (45°C–60°C) and freeze-drying treatments. Comparison with fresh grapefruit peels was also assessed. Significant increases in DPPH, FRAPS, and ABTS values were observed in dried grapefruit peel samples in comparison with fresh peels, indicating the suitability of the treatments for use as tools to greatly enhance the antioxidant potential of these natural byproducts. A total of thirteen flavonoids were quantified in grapefruit peel extracts by HPLC-MS/MS. It was found that naringin, followed by isonaringin, was the main flavonoid occurring in fresh, oven-dried, and freeze-dried grapefruit peels. In vivo assay revealed that fresh and oven-dried grapefruit peel extracts (45°C) exerted a strong cytoprotective effect on SH-SY5Y neuroblastoma cell lines at concentrations ranging within 0.1–0.25 mg/mL. Our data suggest that grapefruit (Citrus paradisi Macf.) peel has considerable potential as a source of natural bioactive flavonoids with outstanding antioxidant activity which can be used as agents in several therapeutic strategies. PMID:26904169

Novel insights into hydrogen sulfide--mediated cytoprotection.

PubMed

Calvert, John W; Coetzee, William A; Lefer, David J

2010-05-15

Hydrogen sulfide (H(2)S) is a colorless, water soluble, flammable gas that has the characteristic smell of rotten eggs. Like other members of the gasotransmitter family (nitric oxide and carbon monoxide), H(2)S has traditionally been considered to be a highly toxic gas and environmental hazard. However, much like for nitric oxide and carbon monoxide, the initial negative perception of H(2)S has evolved with the discovery that H(2)S is produced enzymatically in mammals under normal conditions. As a result of this discovery, there has been a great deal of work to elucidate the physiological role of H(2)S. H(2)S is now recognized to be cytoprotective in various models of cellular injury. Specifically, it has been demonstrated that the acute administration of H(2)S, either prior to ischemia or at reperfusion, significantly ameliorates in vitro or in vivo myocardial and hepatic ischemia-reperfusion injury. These studies have also demonstrated a cardioprotective role for endogenous H(2)S. This review article summarizes the current body of evidence demonstrating the cytoprotective effects of H(2)S with an emphasis on the cardioprotective effects. This review also provides a detailed description of the current signaling mechanisms shown to be responsible for these cardioprotective actions.

Stress Inducibility of SIRT1 and Its Role in Cytoprotection and Cancer

PubMed Central

Raynes, Rachel; Brunquell, Jessica

2013-01-01

Cells must continuously respond to stressful insults via the upregulation of cytoprotective pathways. The longevity factor and deacetylase SIRT1 plays a critical role in coordinating this cellular response to stress. SIRT1 activity and levels are regulated by cellular stressors, including metabolic, genotoxic, oxidative, and proteotoxic stress. As a stress sensor, SIRT1 impacts cell survival by deacetylating substrate proteins to drive the cell towards a cytoprotective pathway. Extreme stress conditions, however, can cause SIRT1 to lead cells down an apoptotic pathway instead. SIRT1 is frequently dysregulated in cancer cells and has been characterized to have a dual role as both an oncogene and a tumor suppressor, likely due to its pivotal function in regulating cytoprotection. Recently, the ability of SIRT1 to regulate HSF1-dependent induction of the heat shock response has highlighted another pathway through which SIRT1 can modulate cytoprotection. Activation of HSF1 results in the production of cytoprotective chaperones that can facilitate the transformed phenotype of cancer cells. In this review, we discuss the stress-dependent regulation of SIRT1. We highlight the role of SIRT1 in stress management and cytoprotection and emphasize SIRT1-dependent activation of HSF1 as a potential mechanism for cancer promotion. PMID:24020008

Cytoprotective Effects of Pumpkin (Cucurbita Moschata) Fruit Extract against Oxidative Stress and Carbonyl Stress.

PubMed

Shayesteh, Reyhaneh; Kamalinejad, Mohammad; Adiban, Hasan; Kardan, Azin; Keyhanfar, Fariborz; Eskandari, Mohammad Reza

2017-10-01

Background Diabetes mellitus is a chronic endocrine disorder that is associated with significant mortality and morbidity due to microvascular and macrovascular complications. Diabetes complications accompanied with oxidative stress and carbonyl stress in different organs of human body because of the increased generation of free radicals and impaired antioxidant defense systems. In the meantime, reactive oxygen species (ROS) and reactive carbonyl species (RCS) have key mediatory roles in the development and progression of diabetes complications. Therapeutic strategies have recently focused on preventing such diabetes-related abnormalities using different natural and chemical compounds. Pumpkin ( Cucurbita moschata ) is one of the most important vegetables in the world with a broad-range of pharmacological activities such as antihyperglycemic effect. Methods In the present study, the cytoprotective effects of aqueous extract of C. moschata fruit on hepatocyte cytotoxicity induced by cumene hydroperoxide (oxidative stress model) or glyoxal (carbonylation model) were investigated using freshly isolated rat hepatocytes. Results The extract of C. moschata (50 μg/ml) excellently prevented oxidative and carbonyl stress markers, including hepatocyte lysis, ROS production, lipid peroxidation, glutathione depletion, mitochondrial membrane potential collapse, lysosomal damage, and cellular proteolysis. In addition, protein carbonylation was prevented by C. moschata in glyoxal-induced carbonyl stress. Conclusion It can be concluded that C. moschata has cytoprotective effects in oxidative stress and carbonyl stress models and this valuable vegetable can be considered as a suitable herbal product for the prevention of toxic subsequent of oxidative stress and carbonyl stress seen in chronic hyperglycemia. © Georg Thieme Verlag KG Stuttgart · New York.

Protection of ATP-depleted cells by impermeant strychnine derivatives: implications for glycine cytoprotection.

PubMed

Dong, Z; Venkatachalam, M A; Weinberg, J M; Saikumar, P; Patel, Y

2001-03-01

Glycine and structurally related amino acids with activities at chloride channel receptors in the central nervous system also have robust protective effects against cell injury by ATP depletion. The glycine receptor antagonist strychnine shares this protective activity. An essential step toward identification of the molecular targets for these compounds is to determine whether they protect cells through interactions with intracellular targets or with molecules on the outer surface of plasma membranes. Here we report cytoprotection by a cell-impermeant derivative of strychnine. A strychnine-fluorescein conjugate (SF) was synthesized, and impermeability of plasma membranes to this compound was verified by fluorescence confocal microscopy. In an injury model of Madin-Darby canine kidney cells, ATP depletion led to lactate dehydrogenase release. SF prevented lactate dehydrogenase leakage without ameliorating ATP depletion. This was accompanied by preservation of cellular ultrastructure and exclusion of vital dyes. SF protection was also shown for ATP-depleted rat hepatocytes. On the other hand, when a key structural motif in the active site of strychnine was chemically blocked, the SF lost its protective effect, establishing strychnine-related specificity for SF protection. Cytoprotective effects of the cell-impermeant strychnine derivative provide compelling evidence suggesting that molecular targets on the outer surface of plasma membranes may mediate cytoprotection by strychnine and glycine.

PDT: loss of autophagic cytoprotection after lysosomal photodamage

NASA Astrophysics Data System (ADS)

Kessel, David; Price, Michael

2012-02-01

Photodynamic therapy is known to evoke both autophagy and apoptosis. Apoptosis is an irreversible death pathway while autophagy can serve a cytoprotective function. In this study, we examined two photosensitizing agents that target lysosomes, although they differ in the reactive oxygen species (ROS) formed during irradiation. With both agents, the 'shoulder' on the PDT dose-response curve was substantially attenuated, consistent with loss of a cytoprotective pathway. In contrast, this 'shoulder' is commonly observed when PDT targets mitochondria or the ER. We propose that lysosomal targets may offer the possibility of promoting PDT efficacy by eliminating a potentially protective pathway.

Anti-inflammatory, antiproliferative and cytoprotective potential of the Attalea phalerata Mart. ex Spreng. pulp oil

PubMed Central

Lescano, Caroline Honaiser; Arrigo, Jucicléia da Silva; Cardoso, Cláudia Andrea Lima; Coutinho, Janclei Pereira; Moslaves, Iluska Senna Bonfá; Ximenes, Thalita Vieira do Nascimento; Kadri, Monica Cristina Toffoli; Weber, Simone Schneider; Perdomo, Renata Trentin; Kassuya, Cândida Aparecida Leite; Vieira, Maria do Carmo; Sanjinez-Argandoña, Eliana Janet

2018-01-01

The anti-inflammatory, antiproliferative and cytoprotective activity of the Attalea phalerata Mart. ex Spreng pulp oil was evaluated by in vitro and in vivo methods. As for the chemical profile, the antioxidant activity was performed by spectrophotometry, and the profile of carotenoids and amino acids by chromatography. Our data demonstrated that A. phalerata oil has high carotenoid content, antioxidant activity and the presence of 5 essential amino acids. In the in vitro models of inflammation, the oil demonstrated the capacity to inhibit COX1 and COX2 enzymes, the production of nitric oxide and also induces macrophages to spreading. In the in vivo models of inflammation, the oil inhibited edema and leukocyte migration in the Wistar rats. In the in vitro model of antiproliferative and cytoprotective activity, the oil was shown inactive against the kidney carcinoma and prostate carcinoma lineage cells and with cytoprotective capacity in murine fibroblast cells, inhibiting the cytotoxic action of doxorubicin. Therefore, it is concluded that A. phalerata pulp oil has anti-inflammatory effects with nutraceutical properties potential due to the rich composition. Moreover, the oil also has cytoprotective activity probably because of its ability to inhibit the action of free radicals. PMID:29634766

Structure-activity relationships of neoechinulin A analogues with cytoprotection against peroxynitrite-induced PC12 cell death.

PubMed

Kimoto, Kuniaki; Aoki, Toshiaki; Shibata, Yasushi; Kamisuki, Shinji; Sugawara, Fumio; Kuramochi, Kouji; Nakazaki, Atsuo; Kobayashi, Susumu; Kuroiwa, Kenji; Watanabe, Nobuo; Arai, Takao

2007-10-01

Neoechinulin A, an alkaloid from Eurotium rubrum Hiji025, protected neuronal PC12 cells against cell death induced by peroxynitrite derived from SIN-1 (3-(4-morpholinyl)sydnonimine hydrochloride). In this study, we investigated the structure-activity relationships of neoechinulin A and a set of its analogues by using assays to measure anti-nitration and antioxidant activities and cytoprotection against SIN-1-induced PC12 cell death. The presence of the diketopiperazine ring was essential for both the antioxidant and anti-nitration activities of neoechinulin A derivatives. Nevertheless, a derivative lacking the diketopiperazine ring could still protect PC12 cells against SIN-1 cytotoxicity. An acyclic analogue completely lost the cytoprotective effect while retaining its antioxidant/anti-nitration activities. Pre-incubation of the cells with neoechinulin A for at least 12 hours was essential for the cells to gain SIN-1 resistance. These results suggest that neoechinulin A endows the cells with cytoprotection through a biological effect different from the apparent antioxidant/anti-nitration activities.

Cytoprotective effects of melatonin on zoledronic acid-treated human mesenchymal stem cells in vitro.

PubMed

Rodríguez-Lozano, Francisco Javier; García-Bernal, David; Ros-Roca, Maria de Los Ángeles; Algueró, Maria del Carmen; Oñate-Sánchez, Ricardo Elías; Camacho-Alonso, Fabio; Moraleda, Jose María

2015-07-01

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a common clinical complication in patients receiving bisphosphonate therapy. Furthermore, melatonin has been proposed as a therapeutic drug for the oral cavity due to its antioxidant properties. This study aimed to evaluate the cytoprotective effects of melatonin on zoledronic acid (ZA)-treated human mesenchymal stem cells from periodontal ligament (PDLSCs) and bone marrow (BMMSCs). PDLSCs and BMMSCs were exposed to ZA, melatonin or ZA + melatonin for 72 h. Cell proliferation was measured by a colorimetric assay, whereas their mesenchymal phenotype was analyzed by flow cytometry. Proliferation assays showed that BMMSCs presented higher ZA resistance than PDLSCs, as well as a difference in response to the simultaneous treatment of ZA + melatonin. Using PDLSCs, high doses of melatonin significantly increased their proliferation, whereas lower concentrations were enough to enhance ZA-treated BMMSC proliferation. Moreover, PDLSCs displayed a CD90/CD105 downregulation and CD73 upregulation in response to ZA, which was more pronounced in response to melatonin. Furthermore, ZA or ZA + low doses of melatonin induced a decrease of expression of CD90/CD105/CD73 on BMMSCs, while a higher concentration recovered CD73 levels. These results suggest that melatonin has a cytoprotective effect on ZA-treated PDLSCs and BMMSCs. Thus, it could be used for BRONJ prevention. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Induction of Cytoprotective Pathways Is Central to the Extension of Lifespan Conferred by Multiple Longevity Pathways

PubMed Central

Shore, David E.; Carr, Christopher E.; Ruvkun, Gary

2012-01-01

Many genetic and physiological treatments that extend lifespan also confer resistance to a variety of stressors, suggesting that cytoprotective mechanisms underpin the regulation of longevity. It has not been established, however, whether the induction of cytoprotective pathways is essential for lifespan extension or merely correlated. Using a panel of GFP-fused stress response genes, we identified the suites of cytoprotective pathways upregulated by 160 gene inactivations known to increase Caenorhabditis elegans longevity, including the mitochondrial UPR (hsp-6, hsp-60), the ER UPR (hsp-4), ROS response (sod-3, gst-4), and xenobiotic detoxification (gst-4). We then screened for other gene inactivations that disrupt the induction of these responses by xenobiotic or genetic triggers, identifying 29 gene inactivations required for cytoprotective gene expression. If cytoprotective responses contribute directly to lifespan extension, inactivation of these genes would be expected to compromise the extension of lifespan conferred by decreased insulin/IGF-1 signaling, caloric restriction, or the inhibition of mitochondrial function. We find that inactivation of 25 of 29 cytoprotection-regulatory genes shortens the extension of longevity normally induced by decreased insulin/IGF-1 signaling, disruption of mitochondrial function, or caloric restriction, without disrupting normal longevity nearly as dramatically. These data demonstrate that induction of cytoprotective pathways is central to longevity extension and identify a large set of new genetic components of the pathways that detect cellular damage and couple that detection to downstream cytoprotective effectors. PMID:22829775

Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects.

PubMed

Berlanga-Acosta, Jorge; Abreu-Cruz, Angel; Herrera, Diana García-Del Barco; Mendoza-Marí, Yssel; Rodríguez-Ulloa, Arielis; García-Ojalvo, Ariana; Falcón-Cama, Viviana; Hernández-Bernal, Francisco; Beichen, Qu; Guillén-Nieto, Gerardo

2017-01-01

Growth hormone-releasing peptides (GHRPs) constitute a group of small synthetic peptides that stimulate the growth hormone secretion and the downstream axis activity. Mounting evidences since the early 1980s delineated unexpected pharmacological cardioprotective and cytoprotective properties for the GHRPs. However, despite intense basic pharmacological research, alternatives to prevent cell and tissue demise before lethal insults have remained as an empty niche in the clinical armamentarium. Here, we have rigorously reviewed the investigational development of GHRPs and their clinical niching perspectives. PubMed/MEDLINE databases, including original research and review articles, were explored. The search design was date escalated from 1980 and included articles in English only. GHRPs bind to two different receptors (GHS-R1a and CD36), which redundantly or independently exert relevant biological effects. GHRPs' binding to CD36 activates prosurvival pathways such as PI-3K/AKT1, thus reducing cellular death. Furthermore, GHRPs decrease reactive oxygen species (ROS) spillover, enhance the antioxidant defenses, and reduce inflammation. These cytoprotective abilities have been revealed in cardiac, neuronal, gastrointestinal, and hepatic cells, representing a comprehensive spectrum of protection of parenchymal organs. Antifibrotic effects have been attributed to some of the GHRPs by counteracting fibrogenic cytokines. In addition, GHRP family members have shown a potent myotropic effect by promoting anabolia and inhibiting catabolia. Finally, GHRPs exhibit a broad safety profile in preclinical and clinical settings. Despite these fragmented lines incite to envision multiple pharmacological uses for GHRPs, especially as a myocardial reperfusion damage-attenuating candidate, this family of "drugable" peptides awaits for a definitive clinical niche.

Radioprotective and cytoprotective activity of Tinospora cordifolia stem enriched extract containing cordifolioside-A

PubMed Central

Patel, Arti; Bigoniya, Papiya; Singh, Chandra Shekhar; Patel, Narayan Singh

2013-01-01

Objectives: The present study was undertaken to evaluate the radioprotective and cytoprotective potential of cordifolioside-A, a primary active constituent of n-butanol fraction of Tinospora Cordifolia (NBTC) against 4 Gy-γ radiation in mice and cyclophosphamide induced genotoxicity. Materials and Methods: Presence of cordifolioside-A in NBTC stem ethanolic extract was confirmed by high performance thin layer chromatography (HPTLC) analysis. Radioprotective activity was evaluated at 80 and 120 mg/kg, intraperitoneal (i.p.) dose of NBTC administered 15 days prior to whole body radiation exposure by observing survival rate, change in body weight, hematology, spleen colony forming unit (CFU), and micronucleus (MN) expression. Cytoprotective activity of NBTC was evaluated at 5, 10, and 15 mg/ml concentrations on Allium cepa root meristem growth against cyclophosphamide. Results: HPTLC analysis of standard cordifolioside A, and NBTC confirmed the presence of cordifolioside-A in NBTC with the retention factor value of 0.86. Administration of NBTC (120 mg/kg, i.p.) produced significant protection against radiation in terms of increased survival rate, body weight retention, hematological parameters, spleen CFU assay (P < 0.01), and decreased MN expression (P < 0.01). Cytoprotectivity was observed maximally at 10 mg/ml NBTC concentration with significant increase in root growth (P < 0.01), non-toxic mitotic index (MI) (65.9%) and lesser chromosomal aberrations (15.4%). NBTC at 10 mg/ml concentration showed very few C-anaphase compared to aberrations like fragmentation, C-anaphase, multipolarity and sticky chromosome in cyclophosphamide alone. Conclusion: The results suggest that enriched NBTC containing cordifolioside-A has a potential in vivo radioprotective effect as well as in vitro cytoprotective activity. PMID:23833365

Cytoprotective, antihyperglycemic and phytochemical properties of Cocos nucifera (L.) inflorescence.

PubMed

Renjith, R S; Chikku, A M; Rajamohan, T

2013-10-01

To analyze the cytoprotective and antidiabetic activities as well as phytochemical composition of the immature inflorescence of Cocos nucifera belonging to the Arecaceae Family. The phytochemical screening of inflorescence was done to determine the major constituents present in Cocos nucifera inflorescence. The free radical scavenging potential of inflorescence extracts were evaluated using in vitro radical scavenging assay models. The phytochemical analyses on inflorescence showed the presence of phenolic compounds, flavonoids, resins and alkaloids. The macronutrient analyses, on the other hand, showed the presence of carbohydrate, proteins and fibers. Administration of the methanol extract of coconut inflorescence to the diabetic rats showed dose dependent reduction in hyperglycemia. The cytoprotective property of coconut inflorescence was evidenced from the acute toxicological evaluation. The levels of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were significantly decreased in the diabetic rats treated with inflorescence when compared with the diabetic control rats. The results obtained from the present study apparently proved the non-toxic nature and the cytoprotective and antihyperglycemic properties of coconut inflorescence. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Cytoprotective nanoparticles by conjugation of a polyhis tagged annexin V to a nanoparticle drug.

PubMed

Chen, Howard H; Yuan, Hushan; Cho, Hoonsung; Sosnovik, David E; Josephson, Lee

2015-02-14

We synthesized a cytoprotective magnetic nanoparticle by reacting a maleimide functionalized Feraheme (FH) with a disulfide linked dimer of a polyhis tagged annexin V. Following reductive cleavage of disulfide, the resulting annexin-nanoparticle (diameter = 28.0 ± 2.0 nm by laser light scattering, 7.6 annexin's/nanoparticle) was cytoprotective to cells subjected to plasma membrane disrupting chemotherapeutic or mechanical stresses, and significantly more protective than the starting annexin V. Annexin-nanoparticles provide an approach to the design of nanomaterials which antagonize the plasma membrane permeability characteristic of necrosis and which may have applications as cytoprotective agents.

The role of membrane cholesterol in determining bile acid cytotoxicity and cytoprotection of ursodeoxycholic acid

PubMed Central

Zhou, Yong; Doyen, Rand; Lichtenberger, Lenard M.

2013-01-01

In cholestatic liver diseases, the ability of hydrophobic bile acids to damage membranes of hepatocytes/ductal cells contributes to their cytotoxicity. However, ursodeoxycholic acid (UDC), a hydrophilic bile acid, is used to treat cholestasis because it protects membranes. It has been well established that bile acids associate with and solubilize free cholesterol (CHOL) contained within the lumen of the gallbladder because of their structural similarities. However, there is a lack of understanding of how membrane CHOL, which is a well-established membrane stabilizing agent, is involved in cytotoxicity of hydrophobic bile acids and the cytoprotective effect of UDC. We utilized phospholipid liposomes to examine the ability of membrane CHOL to influence toxicity of individual bile acids, such as UDC and the highly toxic sodium deoxycholate (SDC), as well as the cytoprotective mechanism of UDC against SDC-induced cytotoxicity by measuring membrane permeation and intramembrane dipole potential. The kinetics of bile acid solubilization of phosphatidylcholine liposomes containing various levels of CHOL was also characterized. It was found that the presence of CHOL in membranes significantly reduced the ability of bile acids to damage synthetic membranes. UDC effectively prevented damaging effects of SDC on synthetic membranes only in the presence of membrane CHOL, while UDC enhances the damaging effects of SDC in the absence of CHOL. This further demonstrates that the cytoprotective effects of UDC depend upon the level of CHOL in the lipid membrane. Thus, changes in cell membrane composition, such as CHOL content, potentially influence the efficacy of UDC as the primary drug used to treat cholestasis. PMID:19150330

Novel PI3K/Akt Inhibitors Screened by the Cytoprotective Function of Human Immunodeficiency Virus Type 1 Tat

PubMed Central

Kim, Dong-Hyun; Kim, Baek

2011-01-01

The PI3K/Akt pathway regulates various stress-related cellular responses such as cell survival, cell proliferation, metabolism and protein synthesis. Many cancer cell types display the activation of this pathway, and compounds inhibiting this cell survival pathway have been extensively evaluated as anti-cancer agents. In addition to cancers, several human viruses, such as HTLV, HPV, HCV and HIV-1, also modulate this pathway, presumably in order to extend the life span of the infected target cells for productive viral replication. The expression of HIV-1 Tat protein exhibited the cytoprotective effect in macrophages and a human microglial cell line by inhibiting the negative regulator of this pathway, PTEN. This cytoprotective effect of HIV-1 appears to contribute to the long-term survival and persistent HIV-1 production in human macrophage reservoirs. In this study we exploited the PI3K/Akt dependent cytoprotective effect of Tat-expressing CHME5 cells. We screened a collection of compounds known to modulate inflammation, and identified three novel compounds: Lancemaside A, Compound K and Arctigenin that abolished the cytoprotective phenotype of Tat-expressing CHME5 cells. All three compounds antagonized the kinase activity of Akt. Further detailed signaling studies revealed that each of these three compounds targeted different steps of the PI3K/Akt pathway. Arctigenin regulates the upstream PI3K enzyme from converting PIP2 to PIP3. Lancemaside A1 inhibited the movement of Akt to the plasma membrane, a critical step for Akt activation. Compound K inhibited Akt phosphorylation. This study supports that Tat-expressing CHME5 cells are an effective model system for screening novel PI3K/Akt inhibitors. PMID:21765914

Cytoprotective effect of polysaccharide isolated from different mushrooms against 7-ketocholesterol induced damage in mouse liver cell line (BNL CL. 2).

PubMed

Kim, Joo-Shin; Chung, Hau Yin; Na, Keun

2007-01-01

Cytoprotective ability of polysaccharides isolated from different edible mushrooms was investigated on the 7-ketocholesterol-induced damaged cell line. Polysaccharide extracts from six different edible mushrooms-Flammulina velutipes, Peurotus ostreatus, Lentinus edodes, Agrocybe aegerita, Agaricus blazei, and Cordyceps militaris- were prepared by hot water extraction and alcohol precipitation. Cytoprotective ability was evaluated by measuring the viable cells of the normal embryonic liver cell line (BNL CL. 2) in the presence of 7-ketocholesterol. At 80 microg/mL of 7-ketocholesterol, cytotoxicity was very high with a loss of 98% of viable cells after 20 h of incubation. With the addition of 200 microg/mL of each polysaccharide isolate to the cell line containing 80 microg/mL of 7-ketocholesterol, polysaccharide isolates from both Flammulina velutipes and Peurotus ostreatus could significantly inhibit the 7-ketochoelsterol-induced cytotoxicity in the cells. But other polysaccharide isolates were not effective in inhibiting cell damage caused by the oxLDL-induced cytotoxicity.

Cytoprotective effect of polysaccharide isolated from different mushrooms against 7-ketocholesterol induced damage in mouse liver cell line (BNL CL. 2)

PubMed Central

Chung, Hau Yin; Na, Keun

2007-01-01

Cytoprotective ability of polysaccharides isolated from different edible mushrooms was investigated on the 7-ketocholesterol-induced damaged cell line. Polysaccharide extracts from six different edible mushrooms-Flammulina velutipes, Peurotus ostreatus, Lentinus edodes, Agrocybe aegerita, Agaricus blazei, and Cordyceps militaris- were prepared by hot water extraction and alcohol precipitation. Cytoprotective ability was evaluated by measuring the viable cells of the normal embryonic liver cell line (BNL CL. 2) in the presence of 7-ketocholesterol. At 80 µg/mL of 7-ketocholesterol, cytotoxicity was very high with a loss of 98% of viable cells after 20 h of incubation. With the addition of 200 µg/mL of each polysaccharide isolate to the cell line containing 80 µg/mL of 7-ketocholesterol, polysaccharide isolates from both Flammulina velutipes and Peurotus ostreatus could significantly inhibit the 7-ketochoelsterol-induced cytotoxicity in the cells. But other polysaccharide isolates were not effective in inhibiting cell damage caused by the oxLDL-induced cytotoxicity. PMID:20368935

Cereblon is recruited to aggresome and shows cytoprotective effect against ubiquitin-proteasome system dysfunction.

PubMed

Sawamura, Naoya; Wakabayashi, Satoru; Matsumoto, Kodai; Yamada, Haruka; Asahi, Toru

2015-09-04

Cereblon (CRBN) is encoded by a candidate gene for autosomal recessive nonsyndromic intellectual disability (ID). The nonsense mutation, R419X, causes deletion of 24 amino acids at the C-terminus of CRBN, leading to mild ID. Although abnormal CRBN function may be associated with ID disease onset, its cellular mechanism is still unclear. Here, we examine the role of CRBN in aggresome formation and cytoprotection. In the presence of a proteasome inhibitor, exogenous CRBN formed perinuclear inclusions and co-localized with aggresome markers. Endogenous CRBN also formed perinuclear inclusions under the same condition. Treatment with a microtubule destabilizer or an inhibitor of the E3 ubiquitin ligase activity of CRBN blocked formation of CRBN inclusions. Biochemical analysis showed CRBN containing inclusions were high-molecular weight, ubiquitin-positive. CRBN overexpression in cultured cells suppressed cell death induced by proteasome inhibitor. Furthermore, knockdown of endogenous CRBN in cultured cells increased cell death induced by proteasome inhibitor, compared with control cells. Our results show CRBN is recruited to aggresome and has functional roles in cytoprotection against ubiquitin-proteasome system impaired condition. Copyright © 2015 Elsevier Inc. All rights reserved.

Induction of Hsp 70 in Vero cells in response to mycotoxins cytoprotection by sub-lethal heat shock and by Vitamin E.

PubMed

El Golli, Emna; Hassen, Wafa; Bouslimi, Amel; Bouaziz, Chayma; Ladjimi, M Moncef; Bacha, Hassen

2006-10-10

This paper analysed the toxicity mechanisms of several mycotoxins using Hsp 70 expression, cytoprotection of Vero cells by sub-lethal heat shock (sub-LHS) and Vitamin E. Our aim was (i) to determine whether Citrinin (CTN), Zearalenone (ZEN) and T2 toxin (T2) could induce the expression of Hsp 70, (ii) to check whether or not elevated levels of Hsp and Vitamin E pre-treatment could provide cytoprotection from these mycotoxins, and finally (iii) to emphasize the eventual involvement of oxidative stress on mycotoxin's toxicity. Our study demonstrated that the three examined mycotoxins induced Hsp 70 expression in a dose-dependent manner. A cytoprotective effect of Hsp 70 was obtained when Vero cells were exposed to sub-lethal heat shock followed by a 12h recovery prior to mycotoxins treatment and evidenced by a reduction of their cytolethality. This cytoprotection suggested that Hsp 70 might constitute an important cellular defence mechanism. A cytoprotective action was also obtained although at lesser extent, when cells were pre-treated with an antioxidant agent, the Vitamin E before mycotoxins treatment. This Vitamin E cytoprotection evoked the involvement of oxidative stress in mycotoxins induced toxicity, which was further, confirmed by the reduction of Hsp 70 expression when cells were pre-treated with Vitamin E prior to mycotoxins. Our data clearly shows that oxidative stress is certainly involved in the toxicity of the three studied mycotoxins, Citrinin, Zearalenone and T2 toxin and may therefore constitutes a relevant part in their toxicities; however, at variable extent from one mycotoxin to another.

Thrombomodulin exerts cytoprotective effect on low-dose UVB-irradiated HaCaT cells

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

Iwata, Masahiro; Laboratory of Vascular Medicine, Department of Cardiovascular and Respiratory Disorders Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520; Kawahara, Ko-ichi

Thrombomodulin (TM) is an endothelial cell surface anticoagulant glycoprotein that performs antimetastatic, angiogenic, adhesive, and anti-inflammatory functions in various tissues. It is also expressed in epidermal keratinocytes. We found that a physiological dose (10 mJ/cm{sup 2}) of mid-wavelength ultraviolet irradiation (UVB) significantly induced TM expression via the p38mitogen-activated protein kinase (MAPK)/cyclic AMP response element (CRE) signaling pathway in the epidermal keratinocyte cell line HaCaT; this shows that TM regulates the survival of HaCaT cells. SB203580, a p38MAPK inhibitor, significantly decreased TM expression and the viability of cells exposed to UVB. Furthermore, overexpression of TM markedly increased cell viability, and itmore » was abrogated by TM small interfering RNA (siRNA), suggesting that TM may play an important role in exerting cytoprotective effect on epidermal keratinocytes against low-dose UVB.« less

Structural requirements for the cytoprotective actions of mono-unsaturated fatty acids in the pancreatic β-cell line, BRIN-BD11

PubMed Central

Dhayal, S; Welters, H J; Morgan, N G

2008-01-01

Background and purpose: Exposure of pancreatic β-cells to long-chain free fatty acids leads to differential responses according to the chain length and degree of unsaturation. In particular, long-chain saturated molecules such as palmitate (C16:0) cause apoptosis, whereas equivalent mono-unsaturated species (for example, palmitoleate (C16:1)) are not overtly toxic. Moreover, mono-unsaturates exert a powerful cytoprotective response against a range of proapoptotic stimuli. However, the structural requirements that determine cytoprotection have not been determined and form the basis of the present study. Experimental approach: BRIN-BD11 and INS-1 β-cells were exposed either to the saturated fatty acid palmitate, or to serum withdrawal, to mediate cytotoxicity. The protective effects of a wide range of mono-unsaturated fatty acid derivatives were tested in cytotoxicity assays. Effector caspase activity was also measured and correlated with viability. Key results: The cytotoxic actions of palmitate were inhibited dose-dependently by long-chain mono-unsaturated fatty acids with a defined potency order C18:1>C16:1≫C14:1. The configuration of the double bond was also important with cis forms being more potent than trans forms. Alkylated mono-unsaturated fatty-acid derivates were also cytoprotective, although their efficacy declined as the alkyl chain length increased. Cytoprotection was achieved rapidly on addition of mono-unsaturates and correlated with a rapid and dramatic inhibition of caspase-3/7 activity in palmitate-treated cells. Conclusions and implications: The data reveal the structural requirements that dictate the cytoprotective actions of mono-unsaturated fatty acids in pancreatic β-cells. Metabolic activation is not required and the data point at the potential involvement of a fatty acid receptor in mediating cytoprotection. PMID:18297101

[Role of membrane lipids in myocardial cytoprotection

NASA Technical Reports Server (NTRS)

Grynberg, A.

2000-01-01

The cardiomyocyte capacity to regulate ATP production to face any change in energy demand is a major determinant of cardiac function. This process is based on a balanced fatty acid (FA) metabolism, because FA is the main fuel of the heart, although the most expensive one in oxygen. The pathway is, however, weakly controlled by the cardiac myocyte which can well regulate FA mitochondrial entry but not cell FA uptake. For this reason, several pathological situations often result from either harmful accumulation of FA and derivatives or excess FA-oxidation. Control of the FA/glucose balance by decreased energy production from FA would thus offer an alternative strategy in the treatment of ischaemia, providing the cardiomyocytes weak ability in handling the non-metabolised FA is controlled. The initiation and the regulation of cardiac contraction both result from membrane activity; the other major role of lipids in the heart is their contribution to membrane homeostasis through phospholipid synthesis pathways and phospholipases. The anti-anginal activity of Trimetazidine, reported as a cytoprotective effect without a haemo-dynamic component; is associated with reduced use of FA for energy. However, accumulation of FA and derivatives has never been observed. Trimetazidine is reported to increase significantly the synthesis of phospholipids without influencing the other lipid classes, thus increasing the incorporation of FA in membrane structures. This cytoprotection appears to be based on the redirection of the use of FA to phospholipid synthesis, which would decrease their availability for energy production. This class of compounds, with the same properties as Trimetazidine, offers a metabolic approach to the treatment of ischaemia.

Anti-inflammatory and cytoprotective effects of selected Pakistani medicinal plants in Helicobacter pylori-infected gastric epithelial cells.

PubMed

Zaidi, Syed Faisal; Muhammad, Jibran Sualeh; Shahryar, Saeeda; Usmanghani, Khan; Gilani, Anwarul-Hassan; Jafri, Wasim; Sugiyama, Toshiro

2012-05-07

Helicobacter pylori infection is associated with gastritis, peptic ulcer, and gastric cancer. Due to its high global prevalence and uprising resistance to available antibiotics, efforts are now directed to identify alternative source to treat and prevent associated disorders. In the present study, effect of selected indigenous medicinal plants of Pakistan was evaluated on the secretion of interleukin-8 (IL-8) and generation of reactive oxygen species (ROS) in a bid to rationalize their medicinal use and to examine the anti-inflammatory and cytoprotective effects in gastric epithelial cells. AGS cells and clinically isolated Helicobacter pylori strain (193C) were employed for co-culture experiments. Anti-Helicobacter pylori activity and cytotoxic effects of the selected plants were determined by serial dilution method and DNA fragmentation assay respectively. ELISA and flow cytometry were performed to evaluate the effect on IL-8 secretion and ROS generation in Helicobacter pylori-infected cells. At 100μg/ml, extracts of Alpinia galangal, Cinnamomum cassia, Cinnamomum tamala, Mentha arvensis, Myrtus communis, Oligochaeta ramose, Polygonum bistorta, Rosa damascena, Ruta graveolens, Syzygium aromaticum, Tamarix dioica, and Terminalia chebula exhibited strong inhibitory activity against IL-8 secretion. Of these, four extracts of Cinnamomum cassia, Myrtus communis, Syzygium aromaticum, and Terminalia chebula markedly inhibited IL-8 secretion at both 50 and 100μg/ml. Cinnamomum cassia was further assessed at different concentrations against Helicobacter pylori and TNF-α stimulated IL-8 secretion, which displayed significant suppression of IL-8 in a concentration-dependent-manner. Among the plants examined against ROS generation, Achillea millefolium, Berberis aristata, Coriandrum sativum, Foeniculum vulgare, Matricaria chamomilla and Prunus domestica demonstrated significant suppression of ROS from Helicobacter pylori-infected cells (p<0.01). Results of the study

PRGF exerts a cytoprotective role in zoledronic acid-treated oral cells.

PubMed

Anitua, Eduardo; Zalduendo, Mar; Troya, María; Orive, Gorka

2016-04-01

Bisphosphonates-related osteonecrosis of the jaw (BRONJ) is a common problem in patients undergoing long-term administration of highly potent nitrogen-containing bisphosphonates (N-BPs). This pathology occurs via bone and soft tissue mechanism. Zoledronic acid (ZA) is the most potent intravenous N-BP used to prevent bone loss in patients with bone dysfunction. The objective of this in vitro study was to evaluate the role of different ZA concentrations on the cells from human oral cavity, as well as the potential of plasma rich in growth factors (PRGF) to overcome the negative effects of this BP. Primary human gingival fibroblasts and primary human alveolar osteoblasts were used. Cell proliferation was evaluated by means of a fluorescence-based method. A colorimetric assay to detect DNA fragmentation undergoing apoptosis was used to determine cell death, and the expression of both NF-κB and pNF-κB were quantified by Western blot analysis. ZA had a cytotoxic effect on both human gingival fibroblasts and human alveolar osteoblasts. This BP inhibits cell proliferation, stimulates apoptosis, and induces inflammation. However, the addition of PRGF suppresses all these negative effects of the ZA. PRGF shows a cytoprotective role against the negative effects of ZA on primary oral cells. At present, there is no definitive treatment for bisphosphonates-related osteonecrosis of the jaw (BRONJ), being mainly palliatives. Our results revealed that PRGF has a cytoprotective role in cells exposed to zoledronic acid, thus providing a reliable adjunctive therapy for the treatment of BRONJ pathology.

Alanyl-glutamine dipeptide restores the cytoprotective stress proteome of mesothelial cells exposed to peritoneal dialysis fluids.

PubMed

Kratochwill, Klaus; Boehm, Michael; Herzog, Rebecca; Lichtenauer, Anton Michael; Salzer, Elisabeth; Lechner, Michael; Kuster, Lilian; Bergmeister, Konstantin; Rizzi, Andreas; Mayer, Bernd; Aufricht, Christoph

2012-03-01

Exposure of mesothelial cells to peritoneal dialysis fluids (PDF) results in cytoprotective cellular stress responses (CSR) that counteract PDF-induced damage. In this study, we tested the hypothesis that the CSR may be inadequate in relevant models of peritoneal dialysis (PD) due to insufficient levels of glutamine, resulting in increased vulnerability against PDF cytotoxicity. We particularly investigated the role of alanyl-glutamine (Ala-Gln) dipeptide on the cytoprotective PDF stress proteome. Adequacy of CSR was investigated in two human in vitro models (immortalized cell line MeT-5A and mesothelial cells derived from peritoneal effluent of uraemic patients) following exposure to heat-sterilized glucose-based PDF (PD4-Dianeal, Baxter) diluted with medium and, in a comparative proteomics approach, at different levels of glutamine ranging from depletion (0 mM) via physiological (0.7 mM) to pharmacological levels (8 mM administered as Ala-Gln). Despite severe cellular injury, expression of cytoprotective proteins was dampened upon PDF exposure at physiological glutamine levels, indicating an inadequate CSR. Depletion of glutamine aggravated cell injury and further reduced the CSR, whereas addition of Ala-Gln at pharmacological level restored an adequate CSR, decreasing cellular damage in both PDF exposure systems. Ala-Gln specifically stimulated chaperoning activity, and cytoprotective processes were markedly enhanced in the PDF stress proteome. Taken together, this study demonstrates an inadequate CSR of mesothelial cells following PDF exposure associated with low and physiological levels of glutamine, indicating a new and potentially relevant pathomechanism. Supplementation of PDF with pharmacological doses of Ala-Gln restored the cytoprotective stress proteome, resulting in improved resistance of mesothelial cells to exposure to PDF. Future work will study the clinical relevance of CSR-mediated cytoprotection.

Cytoprotective effects of phenolic antioxidants and essential fatty acids in human blood monocyte and neuroblastoma cell lines: surrogates for neurological damage in vivo.

PubMed

Young, Julie; Wahle, Klaus W J; Boyle, Susanne P

2008-01-01

Oxidative stress is implicated in the development of a range of neurological diseases. There is increasing interest in the neuroprotective efficacy of antioxidants in modulating such processes with at least one polyphenolic being tested as a prophylactic in Alzheimer's disease. Beneficial effects of adjunctive n-3 polyunsaturated fatty acids with combined intakes of vitamin C and E on both the positive and negative symptoms of schizophrenia have been reported. Robust in vitro systems are desirable, enabling a mechanistic investigation of the molecular mechanisms underpinning such effects and identification of further potentially efficacious nutraceuticals. A comparative study employing a human lymphoblastoid cell line derived from a subject with early onset schizophrenia, a neuroblastoma IMR-32 cell line and the histiocytic lymphoma U937 cell line was undertaken. The cytoprotective effects of two phenols in affording protection to cellular DNA from an oxidative challenge were assessed in untreated and fatty acid treated cell lines. Marked differences in the uptake of fatty acids by the cell types were found and the IMR-32 cell line was most susceptible to the oxidant challenge. Hydroxytyrosol gave significant cytoprotection in all three-cell lines and this possible neuroprotective efficacy warrants further investigation, both in vitro and in vivo.

Cytoprotective effects of atmospheric-pressure plasmas against hypoxia-induced neuronal injuries

NASA Astrophysics Data System (ADS)

Yan, Xu; Meng, Zhaozhong; Ouyang, Jiting; Qiao, Yajun; Li, Jiaxin; Jia, Mei; Yuan, Fang; (Ken Ostrikov, Kostya

2018-02-01

Atmospheric pressure plasma jet (APPJ) has recently been the focus of cytoprotective research due to the physiological roles of ROS and RNS. In the current study, we investigated the effect of APPJ treatment on the hypoxia (1% oxygen) induced cell injuries. SH-SY5Y cells were treated by APPJ for different duration and incubated in normoxic condition (20% oxygen) for 5 h followed by 24 h hypoxia treatment. Cell viability was evaluated by lactate dehydrogenase (LDH) release and further monitored using the electric cell-substrate impedance sensing (ECIS) system after APPJ treatment. Results showed that APPJ could reduce cell injuries after 24 h hypoxia, which was consistent with the ECIS results. Furthermore, extracellular NO and H2O2 production was significantly increased with the APPJ treatment. It was also interesting to find that APPJ treatment reduced SH-SY5Y cells proliferation in the hypoxic microenvironment during the first 20 h of hypoxia. Although more work was still need to clarify whether the cell viability maintenance was related to the cell proliferation during hypoxia, our results provide the first evidence of real-time cell viability changes after APPJ treatment under both normoxic and hypoxic conditions, which could provide evidence for the neuroprotective applications of APPJ.

Synthesis of a Series of Caffeic Acid Phenethyl Amide (CAPA) Fluorinated Derivatives: Comparison of Cytoprotective Effects to Caffeic Acid Phenethyl Ester (CAPE)

DTIC Science & Technology

2010-06-11

the cinnamic acid phenyl ring. Although compound 4c proved to be very cytotoxic in HUVEC over a 24 h period, the toxicity is less apparent over a 5 h...drug development process, as it determines how much of the initial dose actually reaches the target site. Cinnamic acid -derived amides are known to...Synthesis of a series of caffeic acid phenethyl amide (CAPA) fluorinated derivatives: Comparison of cytoprotective effects to caffeic acid phenethyl

Non-steroidal anti-inflammatory and cytoprotective drug co-prescription in general practice. A general practitioner-based survey in France.

PubMed

Clinard, F; Bardou, M; Sgro, C; Lefevre, N; Raphael, F; Paille, F; Dumas, M; Hillon, P; Bonithon-Kopp, C

2001-12-01

Non-steroidal anti-inflammatory drugs (NSAIDs) represent one of the most frequently prescribed drugs. Gastrointestinal damage, the most common side effect of NSAIDs. can be limited by the prescription of cytoprotective agents. In order to assess determinants of NSAID-associated cytoprotective agent prescriptions in primary care practice, we performed a general practitioner (GP)-based study. After a 2-month intensive information campaign, the participation of all GPs of the Côte d'Or (France) administrative area was requested. During a 2-month period, GPs had to return a mailed questionnaire on NSAID prescription for up to ten consecutive patients aged over 18 years who required NSAIDs. This 30-item questionnaire included questions about the patient, the type of NSAID and the GP. GP participation rate was 24%, and 791 prescriptions were provided. GPs who participated in the study were representative of GPs of the area in terms of sex, time elapsed since graduation and GP practice area. Around 80% of the patients included in the study were under the age of 65 years. The proportion of prescriptions combining NSAIDs and gastroprotective agents was 29.5%. Omeprazole accounted for 58% of the coprescriptions and misoprostol for 29%. Independent determinants associated with the co-prescription of a cytoprotective agent were age [odds ratio (OR) 4.1; confidence interval (CI) 95% 2.3 7.4], previous history of poor NSAID tolerance (OR 10.4; CI 95% 5.8-18.6), previous history of moderate to severe digestive disorders (OR 13.4; CI 95% 5.1 35.4) and indication for chronic illness (OR 1.8, CI 95% 1.1-3.1). Prescriptions of cytoprotective drugs were in conformity with official guidelines for 78.3% of the patients. Although around 60% of the patients with risk factors for poor tolerance received a gastroprotective drug, 50% of the patients over 65 years did not receive it. Conversely, nearly 12% of the patients with no risk factors were prescribed cytoprotective agents. Patient

A novel shogaol analog suppresses cancer cell invasion and inflammation, and displays cytoprotective effects through modulation of NF-κB and Nrf2-Keap1 signaling pathways

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

Gan, Fei-Fei; Ling, Hui; Ang, Xiaohui

Natural compounds containing vanilloid and Michael acceptor moieties appear to possess anti-cancer and chemopreventive properties. The ginger constituent shogaol represents one such compound. In this study, the anti-cancer potential of a synthetic novel shogaol analog 3-phenyl-3-shogaol (3-Ph-3-SG) was assessed by evaluating its effects on signaling pathways. At non-toxic concentrations, 3-Ph-3-SG suppressed cancer cell invasion in MDA-MB-231 and MCF-7 breast carcinoma cells through inhibition of PMA-activated MMP-9 expression. At similar concentrations, 3-Ph-3-SG reduced expression of the inflammatory mediators nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and prostanglandin-E{sub 2} (PGE{sub 2}) in RAW 264.7 macrophage-like cells. Inhibition of cancermore » cell invasion and inflammation by 3-Ph-3-SG were mediated through suppression of the nuclear factor-kappaB (NF-κB) signaling pathway. The 3-Ph-3-SG also demonstrated cytoprotective effects by inducing the antioxidant response element (ARE)-driven genes NAD(P)H quinone oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1). Cytoprotection by 3-Ph-3-SG was achieved at least partly through modification of cysteine residues in the E3 ubiquitin ligase substrate adaptor Kelch-like ECH-associated protein 1 (Keap1), which resulted in accumulation of transcription factor NF-E2 p45-related factor 2 (Nrf2). The activities of 3-Ph-3-SG were comparable to those of 6-shogaol, the most abundant naturally-occurring shogaol, and stronger than those of 4-hydroxyl-null deshydroxy-3-phenyl-3-shogaol, which attested the importance of the 4-hydroxy substituent in the vanilloid moiety for bioactivity. In summary, 3-Ph-3-SG is shown to possess activities that modulate stress-associated pathways relevant to multiple steps in carcinogenesis. Therefore, it warrants further investigation of this compound as a promising candidate for use in chemotherapeutic and chemopreventive strategies. - Highlights

Radioadaptive Cytoprotective Pathways in the Mouse Retina

NASA Technical Reports Server (NTRS)

Zanello, Susana B.; Wotring, V.; Theriot, C.; Ploutz-Snyder, R.; Zhang, Y.; Wu, H.

2010-01-01

Exposure to cosmic radiation implies a risk of tissue degeneration. Radiation retinopathy is a complication of radiotherapy and exhibits common features with other retinopathies and neuropathies. Exposure to a low radiation dose elicits protective cellular events (radioadaptive response), reducing the stress of a subsequent higher dose. To assess the risk of radiation-induced retinal changes and the extent to which a small priming dose reduces this risk, we used a mouse model exposed to a source of Cs-137-gamma radiation. Gene expression profiling of retinas from non-irradiated control C57BL/6J mice (C) were compared to retinas from mice treated with a low 50 mGy dose (LD), a high 6 Gy dose (HD), and a combined treatment of 50 mGy (priming) and 6 Gy (challenge) doses (LHD). Whole retina RNA was isolated and expression analysis for selected genes performed by RTqPCR. Relevant target genes associated with cell death/survival, oxidative stress, cellular stress response and inflammation pathways, were analyzed. Cellular stress response genes were upregulated at 4 hr after the challenge dose in LHD retinas (Sirt1: 1.5 fold, Hsf1: 1.7 fold, Hspa1a: 2.5 fold; Hif1a: 1.8 fold, Bag1: 1.7). A similar trend was observed in LD animals. Most antioxidant enzymes (Hmox1, Sod2, Prdx1, Cygb, Cat1) and inflammatory mediators (NF B, Ptgs2 and Tgfb1) were upregulated in LHD and LD retinas. Expression of the pro-survival gene Bcl2 was upregulated in LD (6-fold) and LHD (4-fold) retinas. In conclusion, cytoprotective gene networks activation in the retina suggests a radioadaptive response to a priming irradiation dose, with mitigation of the deleterious effects of a subsequent high dose exposure. The enhancement of these cytoprotective mechanisms has potential value as a countermeasure to ocular alterations caused by radiation alone or in combination with other factors in spaceflight environments.

Possible cytoprotective mechanism in rats of D-002, an anti-ulcerogenic product isolated from beeswax.

PubMed

Carbajal, D; Molina, V; Valdés, S; Arruzazabala, L; Rodeiro, I; Más, R; Magraner, J

1996-08-01

D-002 is an anti-ulcerogenic product, isolated from beeswax, which consists of a well-defined mixture of higher primary aliphatic alcohols. It is highly effective against ethanol-induced ulcers. This study was designed to determine if D-002 shows cytoprotective properties on gastric mucosa in ethanol-induced ulcers. The involvement of endogenous prostaglandins in the protective effect of D-002 was also investigated. When a subulcerogenic dose of indomethacin (10 mg kg-1) was injected simultaneously with oral administration of ethanol, oral pre-treatment with D-002 (5-100 mg kg-1) partially inhibited the gastric protection. D-002 (5 and 25 mg kg-1) administered to normal rats significantly increased the soluble mucus content and also prevented its reduction in rats with ethanol-induced ulcers. In addition, D-002 administered at 5 and 25 mg kg-1 prevented the increase of vascular permeability induced by ethanol (60%) and reduced the concentration of thromboxane B2 (TXB2) in gastric mucosa of rats with ethanol-induced ulcers. These results support the hypothesis that the anti-ulcerogenic properties of D-002 could be related to a cytoprotective mechanism.

Cytoprotective Effect of Hydroalcoholic Extract of Pinus eldarica Bark against H2O2-Induced Oxidative Stress in Human Endothelial Cells

PubMed Central

Babaee, Fatemeh; Safaeian, Leila; Zolfaghari, Behzad; Haghjoo Javanmard, Shaghayegh

2016-01-01

Background: Pinus eldarica is a widely growing pine in Iran consisting of biologically active constituents with antioxidant properties. This study investigates the effect of hydroalcoholic extract of P. eldarica bark against oxidative damage induced by hydrogen peroxide (H2O2) in human umbilical vein endothelial cells (HUVECs). Methods: The total phenolic content of P. eldarica extract was determined using Folin-Ciocalteu method. The cytotoxicity of P. eldarica extract (25-1000 µg/ml) on HUVECs was assessed using 3-(4,5- Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method. Cytoprotective effect of P. eldarica extract (25-500 µg/ml) on H2O2-induced oxidative stress was also evaluated by MTT assay. The intra- and extra-cellular hydroperoxides concentration and ferric reducing antioxidant power (FRAP) were measured in pretreated cells. Results: The total phenolic content of P. eldarica extract was estimated as 37.04±1.8% gallic acid equivalent. P. eldarica extract (25-1000 µg/ml) had no cytotoxic effect on HUVECs viability. The pretreatment of HUVECs with P. eldarica extract at the concentrations of 50-500 µg/ml significantly reduced the cytotoxicity of H2O2. P. eldarica extract decreased hydroperoxides concentration and increased FRAP value in intra-cellular fluid at the concentration range of 100-500 µg/ml and in extra-cellular fluid at the concentration range of 25-500 µg/ml. Conclusions: This study revealed the antioxidant and cytoprotective effects of P. eldarica extract against H2O2-induced oxidative stress in HUVECs. Concerning the high content of phenolic compounds in P. eldarica, more research is needed to evaluate its clinical value in endothelial dysfunction and in other oxidative conditions. PMID:26931383

In vitro cytoprotective effects of acetylsalicylic acid, carprofen, meloxicam, or robenacoxib against apoptosis induced by sodium nitroprusside in canine cruciate ligament cells.

PubMed

Waldherr, Katrin; Zurbriggen, Andreas; Spreng, David E; Forterre, Simone

2012-11-01

To determine whether incubation of cruciate ligament cells with acetylsalicylic acid, carprofen, meloxicam, or robenacoxib provides protection against apoptosis induced by sodium nitroprusside (SNP). Explants of cranial (CCL) and caudal (CaCL) cruciate ligaments from eight 1-day-old Beagles. Primary cultures of CCL and CaCL cells were created via enzymatic dissociation of cruciate explants. Purified cell cultures were incubated for 2 hours without (controls) or with 1 of 3 concentrations of 1 of 4 NSAIDs (10, 100, or 200 μg of acetylsalicylic acid/mL; 0.1, 1, or 10 μg of carprofen/mL; 0.1, 1, or 10 μg of meloxicam/mL; or 0.1, 1, or 10 μg of robenacoxib/mL) and subsequently incubated for 18 hours with 1 of 3 concentrations of SNP in an attempt to induce mild, moderate, or severe cytotoxic effects. Cell viability and apoptosis were analyzed via a cell proliferation assay and flow cytometry, respectively. Prostaglandin E(2) concentrations were measured via an ELISA. Cytoprotective effects of NSAIDs were dependent on the extent of SNP-induced apoptosis and were greatest in CCL and CaCL cell cultures with moderate SNP-induced cytotoxic effects. Preincubation with an NSAID improved cell viability by 15% to 45% when CCL and CaCL cells were subsequently incubated with SNP. Carprofen (10 μg/mL) had the greatest cytoprotective effects for CCL and CaCL cells. Incubation with NSAIDs resulted in a nonsignificant decrease in PGE(2) production from SNP-damaged cells. Results indicated that carprofen, meloxicam, and robenacoxib may reduce apoptosis in cells originating from canine cruciate ligaments.

Long-lasting cytoprotection after pentadecapeptide BPC 157, ranitidine, sucralfate or cholestyramine application in reflux oesophagitis in rats.

PubMed

Sikiric, P; Jadrijevic, S; Seiwerth, S; Sosa, T; Deskovic, S; Perovic, D; Aralica, G; Grabarevic, Z; Rucman, R; Petek, M; Jagic, V; Turkovic, B; Ziger, T; Rotkvic, I; Mise, S; Zoricic, I; Sebecic, B; Patrlj, L; Kocman, B; Sarlija, M; Mikus, D; Separovic, J; Hanzevacki, M; Gjurasin, M; Miklic, P

1999-12-01

Recently, the effectiveness of pentadecapeptide BPC 157 and other anti-ulcer agents, called 'direct cytoprotection', was evidenced in totally gastrectomized rats duodenum challenged with cysteamine 24 h after surgery, and sacrificed 24 h after ulcerogen application. The further focus was on the possibility that this effect could be seen over a more prolonged period (1, 2, 4 weeks), and in other parts of the gastrointestinal tract (i.e. oesophagus). After the removal of the stomach, the oesophagus and jejunum were joined by a termino-lateral anastomosis. The animals were euthanized 7, 14 or 28 d after surgery, when oesophagitis was blindly assessed both macroscopically (percentage of ulcerations areas) and microscopically (percentage of areas of ulcers, regeneration and hyperplasia; number of inflammatory cells - polymorphonuclear and mononuclear). Starting 24 h after surgery, the medication was continuously given in the drinking water, in a volume of 12.5 mL/rat daily, until euthanasia at the end of the observation period, i.e. 7, 14, 28 d following surgery. Based on previous experiments, the doses of agents were daily calculated per kg b.w. as follows: BPC 157 125 mg or 125 ng, cholestyramine 2.5 mg, ranitidine 125 mg, sucralfate 725 mg, whereas controls received 72.5 mL x kg(-1) water. In support of these initial findings, and considering gastrectomized acid-free rats as an ideal model for long-term cytoprotective studies as well, pentadecapeptide BPC 157 markedly attenuated termino-lateral oesophagojejunal anastomosis-reflux oesophagitis also over a quite prolonged period. This efficacy was only partly shared by other anti-ulcer agents. After 1-week-old oesophagitis (microscopical assessment), but not after 2 or 4 weeks, less damaged mucosa was noted in rats drinking ranitidine or sucralfate compared to controls. Similar effectiveness was noted for cholestyramine. The obtained results were supported also by inflammatory cell assessment. Compared with control

Antioxidant and cytoprotective activities of Piper betle, Areca catechu, Uncaria gambir and betel quid with and without calcium hydroxide.

PubMed

Sazwi, Nordin Nur; Nalina, Thurairajah; Abdul Rahim, Zubaidah Haji

2013-12-11

Betel quid chewing is a popular habit in Southeast Asia. It is believed that chewing betel quid could reduce stress, strengthen teeth and maintain oral hygiene. The aim of this study was to investigate the antioxidant and cytoprotective activities of each of the ingredients of betel quid and compared with betel quid itself (with and without calcium hydroxide). The correlation of their cytoprotective and antioxidant activities with phenolic content was also determined. Five samples (betel leaf, areca nut, gambir, betel quid and betel quid containing calcium hydroxide) were extracted in deionized distilled water for 12 hours at 37°C. Antioxidant activities were evaluated for radical scavenging activity using DPPH assay, ferric reducing activity using FRAP assay and lipid peroxidation inhibition activity using FTC assay. Total phenolic content (TPC) was determined using Folin-Ciocalteu procedure. Phenolic composition was analyzed using LC-MS/MS. Cytoprotective activity towards human gingival fibroblast cells was examined using MTT assay. Among the ingredients of betel quid, gambir demonstrated the highest antioxidant (DPPH - IC50 = 6.4 ± 0.8 μg/mL, FRAP - 5717.8 ± 537.6 μmol Fe(II)/mg), total phenolic content (TPC - 1142.5 ± 106.8 μg TAE/mg) and cytoprotective (100.1 ± 4.6%) activities. Betel quid when compared with betel quid containing calcium hydroxide has higher antioxidant (DPPH - IC50 =59.4 ± 4.4 μg/mL, FRAP - 1022.2 ± 235.7 μmol Fe(II)/mg), total phenolic content (TPC - 140.0 ± 22.3 μg TAE/mg), and cytoprotective (113.5 ± 15.9%) activities. However, all of the five samples showed good lipid peroxidation inhibition compared to vitamin E. LC-MS/MS analysis revealed the presence of quinic acid as the major compound of gambir and betel quid. A positive correlation was observed between TPC and radical scavenging (r = 0.972), reducing power (r = 0.981) and cytoprotective activity (r = 0.682). The betel quid has higher TPC, and antioxidant and

Cytoprotection by Endogenous Zinc in the Vertebrate Retina

PubMed Central

Anastassov, Ivan; Ripps, Harris; Chappell, Richard L.

2014-01-01

Our recent studies have shown that endogenous zinc, co-released with glutamate from the synaptic terminals of vertebrate retinal photoreceptors, provides a feedback mechanism that reduces calcium entry and the concomitant vesicular release of glutamate. We hypothesized that zinc feedback may serve to protect the retina from glutamate excitotoxicity, and conducted in vivo experiments on the retina of the skate (Raja erinacea) to determine the effects of removing endogenous zinc by chelation. These studies showed that removal of zinc by injecting the zinc chelator histidine results in inner retinal damage similar to that induced by the glutamate receptor agonist kainic acid. In contrast, when an equimolar quantity of zinc followed the injection of histidine, the retinal cells were unaffected. Our results are a good indication that zinc, co-released with glutamate by photoreceptors, provides an auto-feedback system that plays an important cytoprotective role in the retina. PMID:24286124

Evaluation of the nutraceutical, antioxidant and cytoprotective properties of ripe pistachio (Pistacia vera L., variety Bronte) hulls.

PubMed

Barreca, Davide; Laganà, Giuseppina; Leuzzi, Ugo; Smeriglio, Antonella; Trombetta, Domenico; Bellocco, Ersilia

2016-04-01

Every year tons of pistachio hulls are separated and eliminated, as waste products, from pistachio seeds. In this study the hulls of ripe pistachios were extracted with two organic solvents (ethanol and methanol) and characterized for phenolic composition, antioxidant power and cytoprotective activity. RP-HPLC-DAD-FLU separation enabled us to identify 20 derivatives, including and by far the most abundant gallic acid, 4-hydroxybenzoic acid, protocatechuic acid, naringin, eriodictyol-7-O-glucoside, isorhamnetin-7-O-glucoside, quercetin-3-O-rutinoside, isorhamnetin-3-O-glucoside and catechin. Methanol extraction gave the highest yields for all classes of compounds and presented a higher scavenging activity in all the antioxidant assays performed. The same was found for cytoprotective activity on lymphocytes, lipid peroxidation and protein degradation. These findings highlight the strong antioxidant and cytoprotective activity of the extract components, and illustrate how a waste product can be used as a source of nutraceuticals to employ in manufacturing industry. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antioxidant and cytoprotective activities of Piper betle, Areca catechu, Uncaria gambir and betel quid with and without calcium hydroxide

PubMed Central

2013-01-01

Background Betel quid chewing is a popular habit in Southeast Asia. It is believed that chewing betel quid could reduce stress, strengthen teeth and maintain oral hygiene. The aim of this study was to investigate the antioxidant and cytoprotective activities of each of the ingredients of betel quid and compared with betel quid itself (with and without calcium hydroxide). The correlation of their cytoprotective and antioxidant activities with phenolic content was also determined. Methods Five samples (betel leaf, areca nut, gambir, betel quid and betel quid containing calcium hydroxide) were extracted in deionized distilled water for 12 hours at 37°C. Antioxidant activities were evaluated for radical scavenging activity using DPPH assay, ferric reducing activity using FRAP assay and lipid peroxidation inhibition activity using FTC assay. Total phenolic content (TPC) was determined using Folin-Ciocalteu procedure. Phenolic composition was analyzed using LC-MS/MS. Cytoprotective activity towards human gingival fibroblast cells was examined using MTT assay. Results Among the ingredients of betel quid, gambir demonstrated the highest antioxidant (DPPH - IC50 = 6.4 ± 0.8 μg/mL, FRAP - 5717.8 ± 537.6 μmol Fe(II)/mg), total phenolic content (TPC - 1142.5 ± 106.8 μg TAE/mg) and cytoprotective (100.1 ± 4.6%) activities. Betel quid when compared with betel quid containing calcium hydroxide has higher antioxidant (DPPH - IC50 =59.4 ± 4.4 μg/mL, FRAP - 1022.2 ± 235.7 μmol Fe(II)/mg), total phenolic content (TPC - 140.0 ± 22.3 μg TAE/mg), and cytoprotective (113.5 ± 15.9%) activities. However, all of the five samples showed good lipid peroxidation inhibition compared to vitamin E. LC-MS/MS analysis revealed the presence of quinic acid as the major compound of gambir and betel quid. A positive correlation was observed between TPC and radical scavenging (r = 0.972), reducing power (r = 0.981) and cytoprotective

Cytoprotective Mechanisms Mediated by Polyphenols from Chilean Native Berries against Free Radical-Induced Damage on AGS Cells

PubMed Central

Theoduloz, Cristina; López-Alarcón, Camilo; Dorta, Eva

2017-01-01

The prevalence of cytoprotective mechanisms induced by polyphenols such as activation of intracellular antioxidant responses (ICM) and direct free radical scavenging was investigated in native Chilean species of strawberries, raspberries, and currants. Human gastric epithelial cells were co- and preincubated with polyphenolic-enriched extracts (PEEs) from Chilean raspberries (Rubus geoides), strawberries (Fragaria chiloensis ssp. chiloensis f. chiloensis), and currants (Ribes magellanicum) and challenged with peroxyl and hydroxyl radicals. Cellular protection was determined in terms of cell viability, glyoxalase I and glutathione s-transferases activities, and carboxymethyl lysine (CML) and malondialdehyde levels. Our results indicate that cytoprotection induced by ICM was the prevalent mechanism for Rubus geoides and F. chiloensis. This agreed with increased levels of glyoxalase I and glutathione S-transferase activities in cells preincubated with PEEs. ORAC index indicated that F. chiloensis was the most efficient peroxyl radical scavenger. Moreover, ICM mediated by F. chiloensis was effective in protecting cells from CML accumulation in contrast to the protective effects induced by free radical scavenging. Our results indicate that although both polyphenol-mediated mechanisms can exert protective effects, ICM was the most prevalent in AGS cells. These results suggest a potential use of these native berries as functional food. PMID:28553436

Cytoprotective effect against UV-induced DNA damage and oxidative stress: role of new biological UV filter.

PubMed

Said, T; Dutot, M; Martin, C; Beaudeux, J-L; Boucher, C; Enee, E; Baudouin, C; Warnet, J-M; Rat, P

2007-03-01

The majority of chemical solar filters are cytotoxic, particularly on sensitive ocular cells (corneal and conjunctival cells). Consequently, a non-cytotoxic UV filter would be interesting in dermatology, but more especially in ophthalmology. In fact, light damage to the eye can be avoided thanks to a very efficient ocular antioxidant system; indeed, the chromophores absorb light and dissipate its energy. After middle age, a decrease in the production of antioxidants and antioxidative enzymes appears with accumulation of endogenous molecules that are phototoxic. UV radiations can induce reactive oxygen species formation, leading to various ocular diseases. Because most UV filters are cytotoxic for the eye, we investigated the anti-UV properties of Calophyllum inophyllum oil in order to propose it as a potential vehicle, free of toxicity, with a natural UV filter action in ophthalmic formulation. Calophyllum inophyllum oil, even at low concentration (1/10,000, v/v), exhibited significant UV absorption properties (maximum at 300nm) and was associated with an important sun protection factor (18-22). Oil concentrations up to 1% were not cytotoxic on human conjunctival epithelial cells, and Calophyllum inophyllum oil appeared to act as a cytoprotective agent against oxidative stress and DNA damage (85% of the DNA damage induced by UV radiations were inhibited with 1% Calophyllum oil) and did not induce in vivo ocular irritation (Draize test on New Zealand rabbits). Calophyllum inophyllum oil thus exhibited antioxidant and cytoprotective properties, and therefore might serve, for the first time, as a natural UV filter in ophthalmic preparations.

Manganese oxide particles as cytoprotective, oxygen generating agents.

PubMed

Tootoonchi, Mohammad Hossein; Hashempour, Mazdak; Blackwelder, Patricia L; Fraker, Christopher A

2017-09-01

Cell culture and cellular transplant therapies are adversely affected by oxidative species and radicals. Herein, we present the production of bioactive manganese oxide nanoparticles for the purpose of radical scavenging and cytoprotection. Manganese comprises the core active structure of somatic enzymes that perform the same function, in vivo. Formulated nanoparticles were characterized structurally and surveyed for maximal activity (superoxide scavenging, hydrogen peroxide scavenging with resultant oxygen generation) and minimal cytotoxicity (48-h direct exposure to titrated manganese oxide concentrations). Cytoprotective capacity was tested using cell exposure to hydrogen peroxide in the presence or absence of the nanoparticles. Several ideal compounds were manufactured and utilized that showed complete disproportionation of superoxide produced by the xanthine/xanthine oxidase reaction. Further, the nanoparticles showed catalase-like activity by completely converting hydrogen peroxide into the corresponding concentration of oxygen. Finally, the particles protected cells (murine β-cell insulinoma) against insult from hydrogen peroxide exposure. Based on these observed properties, these particles could be utilized to combat oxidative stress and inflammatory response in a variety of cell therapy applications. Maintaining viability once cells have been removed from their physiological niche, e.g. culture and transplant, demands proper control of critical variables such as oxygenation and removal of harmful substances e.g. reactive oxygen species. Limited catalysts can transform reactive oxygen species into molecular oxygen and, thereby, have the potential to maintain cell viability and function. Among these are manganese oxide particles which are the subject of this study. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Cytoprotection by fructose and other ketohexoses during bile salt-induced apoptosis of hepatocytes.

PubMed

Zeid, I M; Bronk, S F; Fesmier, P J; Gores, G J

1997-01-01

Toxic bile salts cause hepatocyte necrosis at high concentrations and apoptosis at lower concentrations. Although fructose prevents bile salt-induced necrosis, the effect of fructose on bile salt-induced apoptosis is unclear. Our aim was to determine if fructose also protects against bile salt-induced apoptosis. Fructose inhibited glycochenodeoxycholate (GCDC)-induced apoptosis in a concentration-dependent manner with a maximum inhibition of 72% +/- 10% at 10 mmol/L. First, we determined if fructose inhibited apoptosis by decreasing adenosine triphosphate (ATP) and intracellular pH (pHi). Although fructose decreased ATP to <25% of basal values, oligomycin (an ATP synthase inhibitor) did not inhibit apoptosis despite decreasing ATP to similar values. Fructose (10 mmol/L) decreased intracellular pH (pHi) by 0.2 U. However, extracellular acidification (pH 6.8), which decreased hepatocyte pHi 0.35 U and is known to inhibit necrosis, actually potentiated apoptosis 1.6-fold. Fructose cytoprotection also could not be explained by induction of bcl-2 transcription or metal chelation. Because we could not attribute fructose cytoprotection to metabolic effects, alterations in the expression of bcl-2, or metal chelation, we next determined if the poorly metabolized ketohexoses, tagatose and sorbose, also inhibited apoptosis; unexpectedly, both ketohexoses inhibited apoptosis. Because bile salt-induced apoptosis and necrosis are inhibited by fructose, these data suggest that similar processes initiate bile salt-induced hepatocyte necrosis and apoptosis. In contrast, acidosis, which inhibits necrosis, potentiates apoptosis. Thus, ketohexose-sensitive pathways appear to initiate both bile salt-induced cell apoptosis and necrosis, whereas dissimilar, pH-sensitive, effector mechanisms execute these two different cell death processes.

Antioxidant and cytoprotective properties of D-tagatose in cultured murine hepatocytes.

PubMed

Paterna, J C; Boess, F; Stäubli, A; Boelsterli, U A

1998-01-01

D-Tagatose is a zero-energy producing ketohexose that is a powerful cytoprotective agent against chemically induced cell injury. To further explore the underlying mechanisms of cytoprotection, we investigated the effects of D-tagatose on both the generation of superoxide anion radicals and the consequences of oxidative stress driven by prooxidant compounds in intact cells. Primary cultures of hepatocytes derived from male C57BL/6 mice were exposed to the redox cycling drug nitrofurantoin (NFT). Lethal cell injury induced by 300 microM NFT was completely prevented by high concentrations (20 mM) of D-tagatose, whereas equimolar concentrations of glucose, mannitol, or xylose were ineffective. The extent of NFT-induced intracellular superoxide anion radical formation was not altered by D-tagatose, indicating that the ketohexose did not inhibit the reductive bioactivation of NFT. However, the NFT-induced decline of the intracellular GSH content was largely prevented by D-tagatose. The sugar also afforded complete protection against NFT toxicity in hepatocytes that had been chemically depleted of GSH. Furthermore, the ketohexose fully protected from increases in both membrane lipid peroxidation and protein carbonyl formation. In addition, D-tagatose completely prevented oxidative cell injury inflicted by toxic iron overload with ferric nitrilotriacetate (100 microM). In contrast, D-tagatose did not protect against lethal cell injury induced by tert-butyl hydroperoxide, a prooxidant which acts by hydroxyl radical-independent mechanisms and which is partitioned in the lipid bilayer. These results indicate that D-tagatose, which is a weak iron chelator, can antagonize the iron-dependent toxic consequences of intracellular oxidative stress in hepatocytes. The antioxidant properties of D-tagatose may result from sequestering the redox-active iron, thereby protecting more critical targets from the damaging potential of hydroxyl radical.

Chemical sporulation and germination: cytoprotective nanocoating of individual mammalian cells with a degradable tannic acid-FeIII complex

NASA Astrophysics Data System (ADS)

Lee, Juno; Cho, Hyeoncheol; Choi, Jinsu; Kim, Doyeon; Hong, Daewha; Park, Ji Hun; Yang, Sung Ho; Choi, Insung S.

2015-11-01

Individual mammalian cells were coated with cytoprotective and degradable films by cytocompatible processes maintaining the cell viability. Three types of mammalian cells (HeLa, NIH 3T3, and Jurkat cells) were coated with a metal-organic complex of tannic acid (TA) and ferric ion, and the TA-FeIII nanocoat effectively protected the coated mammalian cells against UV-C irradiation and a toxic compound. More importantly, the cell proliferation was controlled by programmed formation and degradation of the TA-FeIII nanocoat, mimicking the sporulation and germination processes found in nature.Individual mammalian cells were coated with cytoprotective and degradable films by cytocompatible processes maintaining the cell viability. Three types of mammalian cells (HeLa, NIH 3T3, and Jurkat cells) were coated with a metal-organic complex of tannic acid (TA) and ferric ion, and the TA-FeIII nanocoat effectively protected the coated mammalian cells against UV-C irradiation and a toxic compound. More importantly, the cell proliferation was controlled by programmed formation and degradation of the TA-FeIII nanocoat, mimicking the sporulation and germination processes found in nature. Electronic supplementary information (ESI) available: Experimental details, LSCM images, and SEM and TEM images. See DOI: 10.1039/c5nr05573c

Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats

PubMed Central

Akbulut, Sami; Elbe, Hulya; Eris, Cengiz; Dogan, Zumrut; Toprak, Gulten; Otan, Emrah; Erdemli, Erman; Turkoz, Yusuf

2014-01-01

AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity. METHODS: An MTX-induced hepatotoxicity model was established in 44 male Sprague Dawley rats by administration of a single intraperitoneal injection of 20 mg/kg MTX. Eleven of the rats were left untreated (Model group; n = 11), and the remaining rats were treated with a 7-d course of 50 mg/kg per day NAC (MTX + NAC group; n = 11), 50 mg/kg per single dose AMF (MTX + AMF group; n = 11), or 10 mg/kg per day ASC (MTX + ASC group; n = 11). Eleven rats that received no MTX and no treatments served as the negative control group. Structural and functional changes related to MTX- and the various treatments were assessed by histopathological analysis of liver tissues and biochemical assays of malondialdehyde (MDA), superoxide dismutase (SOD), catalase, glutathione (GSH) and xanthine oxidase activities and of serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin. RESULTS: Exposure to MTX caused structural and functional hepatotoxicity, as evidenced by significantly worse histopathological scores [median (range) injury score: control group: 1 (0-3) vs 7 (6-9), P = 0.001] and significantly higher MDA activity [409 (352-466) nmol/g vs 455.5 (419-516) nmol/g, P < 0.05]. The extent of MTX-induced perturbation of both parameters was reduced by all three cytoprotective agents, but only the reduction in hepatotoxicity scores reached statistical significance [4 (3-6) for NAC, 4.5 (3-5) for AMF and 6 (5-6) for ASC; P = 0.001, P = 0.001 and P < 0.005 vs model group respectively]. Exposure to MTX also caused a significant reduction in the activities of GSH and SOD antioxidants in liver tissues [control group: 3.02 (2.85-3.43) μmol/g and 71.78 (61.88-97.81) U/g vs model group: 2.52 (2.07-3.34) μmol/g and 61.46 (58

Cytoprotection of human endothelial cells against oxidative stress by 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im): application of systems biology to understand the mechanism of action.

PubMed

Wang, Xinyu; Bynum, James A; Stavchansky, Solomon; Bowman, Phillip D

2014-07-05

Cellular damage from oxidative stress, in particular following ischemic injury, occurs during heart attack, stroke, or traumatic injury, and is potentially reducible with appropriate drug treatment. We previously reported that caffeic acid phenethyl ester (CAPE), a plant-derived polyphenolic compound, protected human umbilical vein endothelial cells (HUVEC) from menadione-induced oxidative stress and that this cytoprotective effect was correlated with the capacity to induce heme oxygenase-1 (HMOX1) and its protein product, a phase II cytoprotective enzyme. To further improve this cytoprotective effect, we studied a synthetic triterpenoid, 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), which is known as a potent phase II enzyme inducer with antitumor and anti-inflammatory activities, and compared it to CAPE. CDDO-Im at 200nM provided more protection to HUVEC against oxidative stress than 20μM CAPE. We explored the mechanism of CDDO-Im cytoprotection with gene expression profiling and pathway analysis and compared to that of CAPE. In addition to potent up-regulation of HMOX1, heat shock proteins (HSP) were also found to be highly induced by CDDO-Im in HUVEC. Pathway analysis results showed that transcription factor Nrf2-mediated oxidative stress response was among the top canonical pathways commonly activated by both CDDO-Im and CAPE. Compared to CAPE, CDDO-Im up-regulated more HSP and some of them to a much higher extent. In addition, CDDO-Im treatment affected Nrf2 pathway more significantly. These findings may provide an explanation why CDDO-Im is a more potent cytoprotectant than CAPE against oxidative stress in HUVEC. Copyright © 2014 Elsevier B.V. All rights reserved.

The Janus face of α-toxin: a potent mediator of cytoprotection in staphylococci-infected macrophages.

PubMed

Koziel, Joanna; Chmiest, Daniela; Bryzek, Danuta; Kmiecik, Katarzyna; Mizgalska, Danuta; Maciag-Gudowska, Agnieszka; Shaw, Lindsey N; Potempa, Jan

2015-01-01

After phagocytosis by macrophages, Staphylococcus aureus evades killing in an α-toxin-dependent manner, and then prevents apoptosis of infected cells by upregulating expression of antiapoptotic genes like MCL-1 (myeloid cell leukemia-1). Here, using purified α-toxin and a set of hla-deficient strains, we show that α-toxin is critical for the induction of MCL-1 expression and the cytoprotection of infected macrophages. Extracellular or intracellular treatment of macrophages with α-toxin alone did not induce cytoprotection conferred by increased Mcl-1, suggesting that the process is dependent on the production of α-toxin by intracellular bacteria. The increased expression of MCL-1 in infected cells was associated with enhanced NFκB activation, and subsequent IL-6 secretion. This effect was only partially inhibited by blocking TLR2, which suggests the participation of intracellular receptors in the specific recognition of S. aureus strains secreting α-toxin. Thus, S. aureus recognition by intracellular receptors and/or activation of downstream pathways leading to Mcl-1 expression is facilitated by α-toxin released by intracellular bacteria which permeabilize phagosomes, ensuring pathogen access to the cytoplasmatic compartment. Given that the intracellular survival of S. aureus depends on α-toxin, we propose a novel role for this agent in the protection of the intracellular niche, and further dissemination of staphylococci by infected macrophages. © 2014 S. Karger AG, Basel.

Cytochrome P450 2A5 and bilirubin: Mechanisms of gene regulation and cytoprotection

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

Kim, Sangsoo Daniel; Antenos, Monica; Squires, E. James

2013-07-15

Bilirubin (BR) has recently been identified as the first endogenous substrate for cytochrome P450 2A5 (CYP2A5) and it has been suggested that CYP2A5 plays a major role in BR clearance as an alternative mechanism to BR conjugation by uridine-diphosphate glucuronyltransferase 1A1. This study investigated the mechanisms of Cyp2a5 gene regulation by BR and the cytoprotective role of CYP2A5 in BR hepatotoxicity. BR induced CYP2A5 expression at the mRNA and protein levels in a dose-dependent manner in primary mouse hepatocytes. BR treatment also caused nuclear translocation of Nuclear factor-E2 p45-related factor 2 (Nrf2) in hepatocytes. In reporter assays, BR treatment ofmore » primary hepatocytes transfected with a Cyp2a5 promoter-luciferase reporter construct resulted in a 2-fold induction of Cyp2a5 reporter activity. Furthermore, cotransfection of the hepatocytes with a Nrf2 expression vector without BR treatment resulted in an increase in Cyp2a5 reporter activity of approximately 2-fold and BR treatment of Nrf2 cotransfectants further increased reporter activity by 4-fold. In addition, site-directed mutation of the ARE in the reporter construct completely abolished both the BR- and Nrf2-mediated increases in reporter activity. The cytoprotective role of CYP2A5 against BR-mediated apoptosis was also examined in Hepa 1–6 cells that lack endogenous CYP2A5. Transient overexpression of CYP2A5 partially blocked BR-induced caspase-3 cleavage in Hepa 1–6 cells. Furthermore, in vitro degradation of BR was increased by microsomes from Hepa 1–6 cells overexpressing CYP2A5 compared to control cells transfected with an empty vector. Collectively, these results suggest that Nrf2-mediated CYP2A5 transactivation in response to BR may provide an additional mechanism for adaptive cytoprotection against BR hepatotoxicity. - Highlights: • The mechanism of Cyp2a5 gene regulation by BR was investigated. • The cytoprotective role of CYP2A5 in BR hepatotoxicity was determined

The unusual amino acid l-ergothioneine is a physiologic cytoprotectant

PubMed Central

Paul, BD; Snyder, SH

2010-01-01

Ergothioneine (ET) is an unusual sulfur-containing derivative of the amino acid, histidine, which is derived exclusively through the diet. Although ET was isolated a century ago, its physiologic function has not been clearly established. Recently, a highly specific transporter for ET (ETT) was identified in mammalian tissues, which explains abundant tissue levels of ET and implies a physiologic role. Using RNA interference, we depleted cells of its transporter. Cells lacking ETT are more susceptible to oxidative stress, resulting in increased mitochondrial DNA damage, protein oxidation and lipid peroxidation. ETT is concentrated in mitochondria, suggesting a specific role in protecting mitochondrial components such as DNA from oxidative damage associated with mitochondrial generation of superoxide. In combating cytotoxic effects of pyrogallol, a known superoxide generator, ET is as potent as glutathione. Because of its dietary origin and the toxicity associated with its depletion, ET may represent a new vitamin whose physiologic roles include antioxidant cytoprotection. PMID:19911007

Selective cytoprotective effect of histamine on doxorubicin-induced hepatic and cardiac toxicity in animal models

PubMed Central

Lamas, DJMartinel; Nicoud, MB; Sterle, HA; Carabajal, E; Tesan, F; Perazzo, JC; Cremaschi, GA; Rivera, ES; Medina, VA

2015-01-01

The aim of the present work was to evaluate the potential protective effect of histamine on Doxorubicin (Dox)-induced hepatic and cardiac toxicity in different rodent species and in a triple-negative breast tumor-bearing mice model. Male Sprague Dawley rats and Balb/c mice were divided into four groups: control (received saline), histamine (5 mg/kg for rats and 1 mg/kg for mice, daily subcutaneous injection starting 24 h before treatment with Dox), Dox (2 mg/kg, intraperitoneally injected three times a week for 2 weeks) and Dox+histamine (received both treatments). Tissue toxicity was evaluated by histopathological studies and oxidative stress and biochemical parameters. The combined effect of histamine and Dox was also investigated in vitro and in vivo in human MDA-MB-231 triple-negative breast cancer model. Heart and liver of Dox-treated animals displayed severe histological damage, loss of tissue weight, increased TBARS levels and DNA damage along with an augment in serum creatine kinase-myocardial band. Pretreatment with histamine prevented Dox-induced tissue events producing a significant preservation of the integrity of both rat and mouse myocardium and liver, through the reduction of Dox-induced oxidative stress and apoptosis. Histamine treatment preserved anti-tumor activity of Dox, exhibiting differential cytotoxicity and increasing the Dox-induced inhibition of breast tumor growth. Findings provide preclinical evidence indicating that histamine could be a promising candidate as a selective cytoprotective agent for the treatment of Dox-induced cardiac and hepatic toxicity, and encourage the translation to clinical practice. PMID:27551485

Up-regulation of Heme Oxygenase-1 by Korean Red Ginseng Water Extract as a Cytoprotective Effect in Human Endothelial Cells

PubMed Central

Yang, Hana; Lee, Seung Eun; Jeong, Seong Il; Park, Cheung-Seog; Jin, Young-Ho; Park, Yong Seek

2011-01-01

Korean red ginseng (KRG) is used worldwide as a popular traditional herbal medicine. KRG has shown beneficial effects on cardiovascular diseases, such as atherosclerosis, diabetes, and hypertension. Up-regulation of a cytoprotective protein, heme oxygenase (HO)-1, is considered to augment the cellular defense against various agents that may induce cytotoxic injury. In the present study, we demonstrate that KRG water extract induces HO-1 expression in human umbilical vein endothelial cells (HUVECs) and possible involvement of the anti-oxidant transcription factor nuclear factor-eythroid 2-related factor 2 (Nrf2). KRG-induced HO-1 expression was examined by western blots, reverse transcriptase polymerase chain reaction and immunofluorescence staining. Specific silencing of Nrf2 genes with Nrf2-siRNA in HUVECs abolished HO-1 expression. In addition, the HO inhibitor zinc protoporphyrin blunted the preventive effect of KRG on H2O2-induced cell death, as demonstrated by terminal transferase dUTP nick end labeling assay. Taken together, these results suggest that KRG may exert a vasculoprotective effect through Nrf2- mediated HO-1 induction in human endothelial cell by inhibition of cell death. PMID:23717080

The Effect of Covalently-Attached ATRP-Synthesized Polymers on Membrane Stability and Cytoprotection in Human Erythrocytes

PubMed Central

Clafshenkel, William P.; Murata, Hironobu; Andersen, Jill; Creeger, Yehuda; Russell, Alan J.

2016-01-01

Erythrocytes have been described as advantageous drug delivery vehicles. In order to ensure an adequate circulation half-life, erythrocytes may benefit from protective enhancements that maintain membrane integrity and neutralize oxidative damage of membrane proteins that otherwise facilitate their premature clearance from circulation. Surface modification of erythrocytes using rationally designed polymers, synthesized via atom-transfer radical polymerization (ATRP), may further expand the field of membrane-engineered red blood cells. This study describes the fate of ATRP-synthesized polymers that were covalently attached to human erythrocytes as well as the effect of membrane engineering on cell stability under physiological and oxidative conditions in vitro. The biocompatible, membrane-reactive polymers were homogenously retained on the periphery of modified erythrocytes for at least 24 hours. Membrane engineering stabilized the erythrocyte membrane and effectively neutralized oxidative species, even in the absence of free-radical scavenger-containing polymers. The targeted functionalization of Band 3 protein by NHS-pDMAA-Cy3 polymers stabilized its monomeric form preventing aggregation in the presence of the crosslinking reagent, bis(sulfosuccinimidyl)suberate (BS3). A free radical scavenging polymer, NHS-pDMAA-TEMPO˙, provided additional protection of surface modified erythrocytes in an in vitro model of oxidative stress. Preserving or augmenting cytoprotective mechanisms that extend circulation half-life is an important consideration for the use of red blood cells for drug delivery in various pathologies, as they are likely to encounter areas of imbalanced oxidative stress as they circuit the vascular system. PMID:27331401

The Effect of Covalently-Attached ATRP-Synthesized Polymers on Membrane Stability and Cytoprotection in Human Erythrocytes.

PubMed

Clafshenkel, William P; Murata, Hironobu; Andersen, Jill; Creeger, Yehuda; Koepsel, Richard R; Russell, Alan J

2016-01-01

Erythrocytes have been described as advantageous drug delivery vehicles. In order to ensure an adequate circulation half-life, erythrocytes may benefit from protective enhancements that maintain membrane integrity and neutralize oxidative damage of membrane proteins that otherwise facilitate their premature clearance from circulation. Surface modification of erythrocytes using rationally designed polymers, synthesized via atom-transfer radical polymerization (ATRP), may further expand the field of membrane-engineered red blood cells. This study describes the fate of ATRP-synthesized polymers that were covalently attached to human erythrocytes as well as the effect of membrane engineering on cell stability under physiological and oxidative conditions in vitro. The biocompatible, membrane-reactive polymers were homogenously retained on the periphery of modified erythrocytes for at least 24 hours. Membrane engineering stabilized the erythrocyte membrane and effectively neutralized oxidative species, even in the absence of free-radical scavenger-containing polymers. The targeted functionalization of Band 3 protein by NHS-pDMAA-Cy3 polymers stabilized its monomeric form preventing aggregation in the presence of the crosslinking reagent, bis(sulfosuccinimidyl)suberate (BS3). A free radical scavenging polymer, NHS-pDMAA-TEMPO˙, provided additional protection of surface modified erythrocytes in an in vitro model of oxidative stress. Preserving or augmenting cytoprotective mechanisms that extend circulation half-life is an important consideration for the use of red blood cells for drug delivery in various pathologies, as they are likely to encounter areas of imbalanced oxidative stress as they circuit the vascular system.

An exceptionally potent inducer of cytoprotective enzymes: elucidation of the structural features that determine inducer potency and reactivity with Keap1.

PubMed

Dinkova-Kostova, Albena T; Talalay, Paul; Sharkey, John; Zhang, Ying; Holtzclaw, W David; Wang, Xiu Jun; David, Emilie; Schiavoni, Katherine H; Finlayson, Stewart; Mierke, Dale F; Honda, Tadashi

2010-10-29

The Keap1/Nrf2/ARE pathway controls a network of cytoprotective genes that defend against the damaging effects of oxidative and electrophilic stress, and inflammation. Induction of this pathway is a highly effective strategy in combating the risk of cancer and chronic degenerative diseases, including atherosclerosis and neurodegeneration. An acetylenic tricyclic bis(cyano enone) bearing two highly electrophilic Michael acceptors is an extremely potent inducer in cells and in vivo. We demonstrate spectroscopically that both cyano enone functions of the tricyclic molecule react with cysteine residues of Keap1 and activate transcription of cytoprotective genes. Novel monocyclic cyano enones, representing fragments of rings A and C of the tricyclic compound, reveal that the contribution to inducer potency of the ring C Michael acceptor is much greater than that of ring A, and that potency is further enhanced by spatial proximity of an acetylenic function. Critically, the simultaneous presence of two cyano enone functions in rings A and C within a rigid three-ring system results in exceptionally high inducer potency. Detailed understanding of the structural elements that contribute to the reactivity with the protein sensor Keap1 and to high potency of induction is essential for the development of specific and selective lead compounds as clinically relevant chemoprotective agents.

Sargassum fusiforme polysaccharides activate antioxidant defense by promoting Nrf2-dependent cytoprotection and ameliorate stress insult during aging.

PubMed

Chen, Peichao; He, Dan; Zhang, Ya; Yang, Shanshan; Chen, Liujun; Wang, Shengqin; Zou, Huixi; Liao, Zhiyong; Zhang, Xu; Wu, Mingjiang

2016-11-09

Aging is a complex issue, which results in a progressive decline process in cellular protection and physiological functions. Illustrating the causes of aging and pharmaceutical interference with the aging process has been a pivotal issue for thousands of years. Sargassum fusiforme (S. fusiforme), a kind of brown alga, is also named the "longevity vegetable" as it is not only a kind of food, but also used as an herb in traditional Chinese Medicine for maintaining health and treatment of thyroid disease, cardiovascular disease and so on. But how S. fusiforme promotes longevity is vastly equivocal. We got clues from S. fusiforme polysaccharides, which exhibited antioxidant activity, but the underlying mechanisms remained unclear. In this study, we evaluated the antioxidant effect and the possible mechanisms that S. fusiforme polysaccharides have against d-galactose-induced aging and chronic aging. We selected the SFPS as the candidate for antioxidant defense evaluation, which is a type of S. fusiforme polysaccharide with strong free radical scavenging activity and non-toxicity. It revealed that the antioxidant defense of the d-galactose-induced mice was markedly recovered when they were intragastrically administrated with the SFPS. However, oxidative damage may not be the only cause of aging. We further evaluated the function of the SFPS in the chronic aging mice. Intriguingly, we even found an obvious aging phenotype in the middle aged male ICR mice, which showed a significant decline in Nrf2-dependent cytoprotection. When 9-month old male ICR mice were treated with the SFPS for 2 months or even 11 months to their mean survival age, experimental measurements showed that the SFPS significantly promoted the antioxidant defense and mitochondrial integrity during aging. Furthermore, we suggest that the SFPS promotes Nrf2-dependent cytoprotection by upregulating the nuclear Nrf2 translocation, which may be mediated by p21 and JNK dependent pathways. These results suggest

Cytoprotective function of heme oxygenase 1 induced by a nitrated cyclic nucleotide formed during murine salmonellosis.

PubMed

Zaki, Mohammad Hasan; Fujii, Shigemoto; Okamoto, Tatsuya; Islam, Sabrina; Khan, Shahzada; Ahmed, Khandaker Ahtesham; Sawa, Tomohiro; Akaike, Takaaki

2009-03-15

Signaling mechanisms of NO-mediated host defense are yet to be elucidated. In this study, we report a unique signal pathway for cytoprotection during Salmonella infection that involves heme oxygenase 1 (HO-1) induced by a nitrated cyclic nucleotide, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP). Wild-type C57BL/6 mice and C57BL/6 mice lacking inducible NO synthase (iNOS) were infected with Salmonella enterica serovar Typhimurium LT2. HO-1 was markedly up-regulated during the infection, the level being significantly higher in wild-type mice than in iNOS-deficient mice. HO-1 up-regulation was associated with 8-nitro-cGMP formation detected immunohistochemically in Salmonella-infected mouse liver and peritoneal macrophages. 8-Nitro-cGMP either exogenously added or formed endogenously induced HO-1 in cultured macrophages infected with Salmonella. HO-1 inhibition by polyethylene glycol-conjugated zinc-protoporphyrin IX impaired intracellular killing of bacteria in mouse liver and in both RAW 264 cells and peritoneal macrophages. Infection-associated apoptosis was also markedly increased in polyethylene glycol-conjugated zinc-protoporphyrin IX-treated mouse liver cells and cultured macrophages. This effect of HO-1 inhibition was further confirmed by using HO-1 short interfering RNA in peritoneal macrophages. Our results suggest that HO-1 induced by NO-mediated 8-nitro-cGMP formation contributes, via its potent cytoprotective function, to host defense during murine salmonellosis.

[COMPARISON OF CYTOPROTECTIVE EFFECTS OF HEMANTANE AND AMANTADINE UNDER CONDITIONS OF 6-HYDROXYDOPAMINE NEUROTOXIN ACTION ON CULTURED HUMAN NEUROBLASTOMA CELLS].

PubMed

Logvinov, I O; Antipova, T A; Nepoklonov, A V; Valdman, E A

2016-01-01

Potential neuroprotective activity of the novel antiparkinsonian drug hemantane (hydrochloride N-2-(adamantyl)-hexamethylenimine) in comparison to amantadine has been studied in various regimes of administration on human neuroblastoma SH-SY5Y cell line injury induced by 6-hydroxydopamine (6-OHDA), which is used as in vitro model of dopaminergic neurons for Parkinson's disease. Two regimes of hemantane and amantadine administration in a range of final concentrations 10⁻⁶-10⁻⁸ M were used either prior to or immediately after 6-OHDA introduction. MTT colorimetric assay was used to assess the viability of test cells. Significant decrease in viability of SH-SY5Y cells treated with 6-OHDA was observed. The addition of hemantane to cell medium produced cytoprotective effects in both regimes of administration--before and after 6-OHDA--at concentrations 10⁻⁷ M and 10⁻⁶-10⁻⁸ M, respectively. Amantadine in con- centrations 10⁻⁷-10⁻⁸ M was effective to increase cell survival only when administered after 6-OHDA. These results show that hemantane has a greater neu-roprotective potential in comparison to amantadine.

Cytoprotective and pro-angiogenic functions of thrombomodulin are preserved in the C loop of the fifth epidermal growth factor-like domain.

PubMed

Wang, Xiangmin; Pan, Bin; Honda, Goichi; Wang, Xintao; Hashimoto, Yuko; Ohkawara, Hiroshi; Xu, Kailin; Zeng, Lingyu; Ikezoe, Takayuki

2018-06-14

We previously found that the fifth epidermal growth factor-like domain of thrombomodulin (TME5) exerts cytoprotective and pro-angiogenic functions via G-protein coupled receptor 15 (GPR15). TME5 is comprised of three S-S bonds that divide it into three loops: A (TME5A), B (TME5B), and C (TME5C). Here, we identified the minimum structure of TME5 that produces favorable effects in vascular endothelial cells (ECs). We found that TME5C, composed of 19 amino acids, but not TME5A or TME5B, stimulated the proliferation of human umbilical vein endothelial cells (HUVECs) and human hepatic sinusoidal endothelial cells (HHSECs). Matrigel plug assays showed that TME5C stimulates in vivo angiogenesis. In addition, TME5C counteracted calcineurin inhibitor-induced apoptosis and vascular permeability in HUVECs and HHSECs. Western blot analysis indicated that exposure of either HUVECs or HHSECs to TME5C increased the levels of anti-apoptotic myeloid cell leukemia-1 protein in association with the activation of signal transduction pathways, including extracellular signal-regulated kinase, AKT, and mitogen-activated protein kinase p38. Importantly, TME5C did not affect the coagulation pathway in vitro. The cytoprotective function of TME5C was mediated by cell surface-expressed GPR15, as TME5C was not able to protect vascular ECs isolated from GPR15 knock-out mice. Strikingly, TME5C successfully ameliorated sinusoidal obstruction syndrome in a murine model by counteracting the reduction of sinusoidal ECs numbers. Taken together, the cytoprotective and pro-angiogenetic functions of TM are preserved in TME5C. Use of TME5C may be a promising treatment strategy to prevent or treat lethal complications such as sinusoidal obstruction syndrome whose pathogenesis is based on endothelial insults. Copyright © 2018, Ferrata Storti Foundation.

40 CFR 262.21 - Manifest tracking numbers, manifest printing, and obtaining manifests.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Manifest tracking numbers, manifest printing, and obtaining manifests. 262.21 Section 262.21 Protection of Environment ENVIRONMENTAL PROTECTION..., scanned, or faxed, except that the marginal words indicating copy distribution must be printed with a...

40 CFR 262.21 - Manifest tracking numbers, manifest printing, and obtaining manifests.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Manifest tracking numbers, manifest printing, and obtaining manifests. 262.21 Section 262.21 Protection of Environment ENVIRONMENTAL PROTECTION..., scanned, and faxed, except that the marginal words indicating copy distribution must be in red ink. (5...

40 CFR 262.21 - Manifest tracking numbers, manifest printing, and obtaining manifests.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 27 2012-07-01 2012-07-01 false Manifest tracking numbers, manifest printing, and obtaining manifests. 262.21 Section 262.21 Protection of Environment ENVIRONMENTAL PROTECTION..., scanned, or faxed, except that the marginal words indicating copy distribution must be printed with a...

40 CFR 262.21 - Manifest tracking numbers, manifest printing, and obtaining manifests.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 27 2013-07-01 2013-07-01 false Manifest tracking numbers, manifest printing, and obtaining manifests. 262.21 Section 262.21 Protection of Environment ENVIRONMENTAL PROTECTION..., scanned, or faxed, except that the marginal words indicating copy distribution must be printed with a...

Co-evolution of proteins and solutions: protein adaptation versus cytoprotective micromolecules and their roles in marine organisms.

PubMed

Yancey, Paul H; Siebenaller, Joseph F

2015-06-01

Organisms experience a wide range of environmental factors such as temperature, salinity and hydrostatic pressure, which pose challenges to biochemical processes. Studies on adaptations to such factors have largely focused on macromolecules, especially intrinsic adaptations in protein structure and function. However, micromolecular cosolutes can act as cytoprotectants in the cellular milieu to affect biochemical function and they are now recognized as important extrinsic adaptations. These solutes, both inorganic and organic, have been best characterized as osmolytes, which accumulate to reduce osmotic water loss. Singly, and in combination, many cosolutes have properties beyond simple osmotic effects, e.g. altering the stability and function of proteins in the face of numerous stressors. A key example is the marine osmolyte trimethylamine oxide (TMAO), which appears to enhance water structure and is excluded from peptide backbones, favoring protein folding and stability and counteracting destabilizers like urea and temperature. Co-evolution of intrinsic and extrinsic adaptations is illustrated with high hydrostatic pressure in deep-living organisms. Cytosolic and membrane proteins and G-protein-coupled signal transduction in fishes under pressure show inhibited function and stability, while revealing a number of intrinsic adaptations in deep species. Yet, intrinsic adaptations are often incomplete, and those fishes accumulate TMAO linearly with depth, suggesting a role for TMAO as an extrinsic 'piezolyte' or pressure cosolute. Indeed, TMAO is able to counteract the inhibitory effects of pressure on the stability and function of many proteins. Other cosolutes are cytoprotective in other ways, such as via antioxidation. Such observations highlight the importance of considering the cellular milieu in biochemical and cellular adaptation. © 2015. Published by The Company of Biologists Ltd.

Calcium-dependent nitric oxide production is involved in the cytoprotective properties of n-acetylcysteine in glycochenodeoxycholic acid-induced cell death in hepatocytes

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

Gonzalez-Rubio, Sandra; Linares, Clara I.; Bello, Rosario I.

The intracellular oxidative stress has been involved in bile acid-induced cell death in hepatocytes. Nitric oxide (NO) exerts cytoprotective properties in glycochenodeoxycholic acid (GCDCA)-treated hepatocytes. The study evaluated the involvement of Ca{sup 2+} on the regulation of NO synthase (NOS)-3 expression during N-acetylcysteine (NAC) cytoprotection against GCDCA-induced cell death in hepatocytes. The regulation of Ca{sup 2+} pools (EGTA or BAPTA-AM) and NO (L-NAME or NO donor) production was assessed during NAC cytoprotection in GCDCA-treated HepG2 cells. The stimulation of Ca{sup 2+} entrance was induced by A23187 in HepG2. Cell death, Ca{sup 2+} mobilization, NOS-1, -2 and -3 expression, AP-1 activation,more » and NO production were evaluated. GCDCA reduced intracellular Ca{sup 2+} concentration and NOS-3 expression, and enhanced cell death in HepG2. NO donor prevented, and L-NAME enhanced, GCDCA-induced cell death. The reduction of Ca{sup 2+} entry by EGTA, but not its release from intracellular stores by BAPTA-AM, enhanced cell death in GCDCA-treated cells. The stimulation of Ca{sup 2+} entrance by A23187 reduced cell death and enhanced NOS-3 expression in GCDCA-treated HepG2 cells. The cytoprotective properties of NAC were related to the recovery of intracellular Ca{sup 2+} concentration, NOS-3 expression and NO production induced by GCDCA-treated HepG2 cells. The increase of NO production by Ca{sup 2+}-dependent NOS-3 expression during NAC administration reduces cell death in GCDCA-treated hepatocytes.« less

Cytoprotection of Human Endothelial Cells Against Oxidative Stress by 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im): Application of Systems Biology to Understand the Mechanism of Action

DTIC Science & Technology

2014-04-03

and exogenous oxidants, electrophiles , and toxicants. Activation of this pathway was reported to facilitate the induction of HMOX1 (Heiss et al., 2009...cytoprotective effect of caffeic acid phenethyl ester (CAPE) and fluorinated derivatives: effects on heme oxygenase-1 induction and antioxidant

Assessment of Antioxidant and Cytoprotective Potential of Jatropha (Jatropha curcas) Grown in Southern Italy

PubMed Central

Papalia, Teresa; Barreca, Davide; Panuccio, Maria Rosaria

2017-01-01

Jatropha (Jatropha curcas L.) is a plant native of Central and South America, but widely distributed in the wild or semi-cultivated areas in Africa, India, and South East Asia. Although studies are available in literature on the polyphenolic content and bioactivity of Jatropha curcas L., no information is currently available on plants grown in pedoclimatic and soil conditions different from the autochthon regions. The aim of the present work was to characterize the antioxidant system developed by the plant under a new growing condition and to evaluate the polyphenol amount in a methanolic extract of leaves. Along with these analyses we have also tested the antioxidant and cytoprotective activities on lymphocytes. RP-HPLC-DAD analysis of flavonoids revealed a chromatographic profile dominated by the presence of flavone C-glucosydes. Vitexin is the most abundant identified compound followed by vicenin-2, stellarin-2, rhoifolin, and traces of isovitexin and isorhoifolin. Methanolic extract had high scavenging activity in all antioxidant assays tested and cytoprotective activity on lymphocytes exposed to tertz-buthylhydroperoxide. The results highlighted a well-defined mechanism of adaptation of the plant and a significant content of secondary metabolites with antioxidant properties, which are of interest for their potential uses, especially as a rich source of biologically active products. PMID:28335473

Assessment of Antioxidant and Cytoprotective Potential of Jatropha (Jatropha curcas) Grown in Southern Italy.

PubMed

Papalia, Teresa; Barreca, Davide; Panuccio, Maria Rosaria

2017-03-18

Jatropha ( Jatropha curcas L.) is a plant native of Central and South America, but widely distributed in the wild or semi-cultivated areas in Africa, India, and South East Asia. Although studies are available in literature on the polyphenolic content and bioactivity of Jatropha curcas L., no information is currently available on plants grown in pedoclimatic and soil conditions different from the autochthon regions. The aim of the present work was to characterize the antioxidant system developed by the plant under a new growing condition and to evaluate the polyphenol amount in a methanolic extract of leaves. Along with these analyses we have also tested the antioxidant and cytoprotective activities on lymphocytes. RP-HPLC-DAD analysis of flavonoids revealed a chromatographic profile dominated by the presence of flavone C -glucosydes. Vitexin is the most abundant identified compound followed by vicenin-2, stellarin-2, rhoifolin, and traces of isovitexin and isorhoifolin. Methanolic extract had high scavenging activity in all antioxidant assays tested and cytoprotective activity on lymphocytes exposed to tertz-buthylhydroperoxide. The results highlighted a well-defined mechanism of adaptation of the plant and a significant content of secondary metabolites with antioxidant properties, which are of interest for their potential uses, especially as a rich source of biologically active products.

An Organ System Approach to Explore the Antioxidative, Anti-Inflammatory, and Cytoprotective Actions of Resveratrol

PubMed Central

Bath, Sundeep

2015-01-01

Resveratrol is a phenolic phytochemical, with a stilbene backbone, derived from edible plants such as grape and peanut. It is a bioactive molecule with physiological effects on multiple organ systems. Its effects range from the neuroprotective to the nephroprotective, including cardiovascular, neuronal, and antineoplastic responses as a part of its broad spectrum of action. In this review, we examine the effects of resveratrol on the following organ systems: the central nervous system, including neurological pathology such as Parkinson's and Alzheimer's disease; the cardiovascular system, including disorders such as atherosclerosis, ischemia-reperfusion injury, and cardiomyocyte hypertrophy; the kidneys, including primary and secondary nephropathies and nephrolithiasis; multiple forms of cancer; and metabolic syndromes including diabetes. We emphasize commonalities in extracellular matrix protein alterations and intracellular signal transduction system induction following resveratrol treatment. We summarize the known anti-inflammatory, antioxidative, and cytoprotective effects of resveratrol across disparate organ systems. Additionally, we analyze the available literature regarding the pharmacokinetics of resveratrol formulations used in these studies. Finally, we critically examine select clinical trials documenting a lack of effect following resveratrol treatment. PMID:26180596

NF-κB-dependent transcriptional upregulation of cyclin D1 exerts cytoprotection against hypoxic injury upon EGFR activation

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

Chen, Zhi-Dong; Xu, Liang; Tang, Kan-Kai

Apoptosis of neural cells is one of the main pathological features in hypoxic/ischemic brain injury. Nuclear factor-κB (NF-κB) might be a potential therapeutic target for hypoxic/ischemic brain injury since NF-κB has been found to be inactivated after hypoxia exposure, yet the underlying molecular mechanisms of NF-κB inactivation are largely unknown. Here we report that epidermal growth factor receptor (EGFR) activation prevents neuron-like PC12 cells apoptosis in response to hypoxia via restoring NF-κB-dependent transcriptional upregulation of cyclin D1. Functionally, EGFR activation by EGF stimulation mitigates hypoxia-induced PC12 cells apoptosis in both dose- and time-dependent manner. Of note, EGFR activation elevates IKKβmore » phosphorylation, increases IκBα ubiquitination, promotes P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as upregulates cyclin D1 expression. EGFR activation also abrogates the decrease of IKKβ phosphorylation, reduction of IκBα ubiquitination, blockade of P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as downregulation of cyclin D1 expression induced by hypoxia. Furthermore, NF-κB-dependent upregulation of cyclin D1 is instrumental for the EGFR-mediated cytoprotection against hypoxic apoptosis. In addition, the dephosphorylation of EGFR induced by either EGF siRNA transfection or anti-HB-EGF neutralization antibody treatment enhances hypoxic cytotoxicity, which are attenuated by EGF administration. Our results highlight the essential role of NF-κB-dependent transcriptional upregulation of cyclin D1 in EGFR-mediated cytoprotective effects under hypoxic preconditioning and support further investigation of EGF in clinical trials of patients with hypoxic/ischemic brain injury. - Highlights: • EGFR activation significantly decreases hypoxia-induced PC12 cells injury. • EGFR activation abrogates the transcriptional repression of cyclin D1 induced by hypoxia in a

Mechanism of phytoestrogen puerarin-mediated cytoprotection following oxidative injury: Estrogen receptor-dependent up-regulation of PI3K/Akt and HO-1

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

Hwang, Yong Pil; Jeong, Hye Gwang

2008-12-15

Phytoestrogens are polyphenolic non-steroidal plant compounds with estrogen-like biological activity. The phytoestrogen puerarin, the main isoflavone glycoside found in the root of Pueraria lobata, has been used for various medicinal purposes in traditional Chinese medicines for thousands of years. Recent studies have indicated that the estrogen receptor (ER), through interaction with p85, regulates phosphoinositide 3-kinase (PI3K) activity, revealing a physiologic, non-nuclear function of ER that may be relevant in cytoprotection. In this study, we demonstrate that the phytoestrogen puerarin inhibits tert-butyl hydroperoxide (t-BHP)-induced oxidative injury via an ER-dependent G{beta}1/PI3K/Akt and heme oxygenase-1 (HO-1) pathway. Pretreatment of Hepa1c1c7 and HepG2 cellsmore » with puerarin significantly reduced t-BHP-induced caspase-3 activation and subsequent cell death. Also, puerarin up-regulated HO-1 expression and this expression conferred cytoprotection against oxidative injury induced by t-BHP. Moreover, puerarin induced Nrf2 nuclear translocation, which is upstream of puerarin-induced HO-1 expression, and PI3K activation, a pathway that is involved in induced Nrf2 nuclear translocation, HO-1 expression and cytoprotection. Puerarin-induced up-regulation of HO-1 and cytoprotection against t-BHP were abolished by silencing Nrf2 expression with specific siRNA. Also, puerarin-mediated increases in PI3K activation and HO-1 induction were reversed by co-treatment with ICI 182,780 and pertussis toxin. Taken together, these results suggest that puerarin augments cellular antioxidant defense capacity through ER-dependent HO-1 induction via the G{beta}1/PI3K/Akt-Nrf2 signaling pathway, thereby protecting cells from oxidative stress.« less

Efficacy ranking of triterpenoids as inducers of a cytoprotective enzyme and as inhibitors of a cellular inflammatory response via their electron affinity and their electrophilicity index

PubMed Central

Bensasson, René V.; Zoete, Vincent; Berthier, Gaston; Talalay, Paul; Dinkova-Kostova, Albena T.

2010-01-01

Electron affinity (EA) and electrophilicity index (ω) of 16 synthetic triterpenoids (TP), previously identified as inducers of cytoprotective enzymes and as inhibitors of cellular inflammatory responses, have been calculated by the molecular orbital method. Linear correlations were obtained by plotting the values of EA, as well as those of ω versus (i) the potencies of induction of NAD(P)H quinone reductase (NQO1, EC 1.6.99.2), a cytoprotective enzyme, expressed via the concentration of TP required to double the specific activity of NQO1 (CD value) and (ii) the values of their anti-inflammatory activity expressed via the IC-50 of TP for suppression of upregulation of inducible nitric oxide synthase (iNOS, EC 1.14.13.39), both previously experimentally determined. The observed correlations demonstrate quantitatively for a series of triterpenoids that their electrophilicity is a major factor determining their potency as inducers of the cytoprotective phase 2 response and as inhibitors of inflammatory processes. PMID:20433811

Distinct cytoprotective roles of pyruvate and ATP by glucose metabolism on epithelial necroptosis and crypt proliferation in ischaemic gut

PubMed Central

Huang, Ching‐Ying; Kuo, Wei‐Ting; Huang, Chung‐Yen; Lee, Tsung‐Chun; Chen, Chin‐Tin; Peng, Wei‐Hao; Lu, Kuo‐Shyan; Yang, Chung‐Yi

2016-01-01

Key points Intestinal ischaemia causes epithelial death and crypt dysfunction, leading to barrier defects and gut bacteria‐derived septic complications.Enteral glucose protects against ischaemic injury; however, the roles played by glucose metabolites such as pyruvate and ATP on epithelial death and crypt dysfunction remain elusive.A novel form of necrotic death that involves the assembly and phosphorylation of receptor interacting protein kinase 1/3 complex was found in ischaemic enterocytes.Pyruvate suppressed epithelial cell death in an ATP‐independent manner and failed to maintain crypt function. Conversely, replenishment of ATP partly restored crypt proliferation but had no effect on epithelial necroptosis in ischaemic gut.Our data argue against the traditional view of ATP as the main cytoprotective factor by glucose metabolism, and indicate a novel anti‐necroptotic role of glycolytic pyruvate under ischaemic stress. Abstract Mesenteric ischaemia/reperfusion induces epithelial death in both forms of apoptosis and necrosis, leading to villus denudation and gut barrier damage. It remains unclear whether programmed cell necrosis [i.e. receptor‐interacting protein kinase (RIP)‐dependent necroptosis] is involved in ischaemic injury. Previous studies have demonstrated that enteral glucose uptake by sodium‐glucose transporter 1 ameliorated ischaemia/reperfusion‐induced epithelial injury, partly via anti‐apoptotic signalling and maintenance of crypt proliferation. Glucose metabolism is generally assumed to be cytoprotective; however, the roles played by glucose metabolites (e.g. pyruvate and ATP) on epithelial cell death and crypt dysfunction remain elusive. The present study aimed to investigate the cytoprotective effects exerted by distinct glycolytic metabolites in ischaemic gut. Wistar rats subjected to mesenteric ischaemia were enterally instilled glucose, pyruvate or liposomal ATP. The results showed that intestinal ischaemia caused RIP1�

Neurologic manifestations of electrolyte disturbances.

PubMed

Riggs, Jack E

2002-02-01

Electrolyte disturbances occur commonly and are associated with a variety of characteristic neurologic manifestations involving both the central and peripheral nervous systems. Electrolyte disturbances are essentially always secondary processes. Effective management requires identification and treatment of the underlying primary disorder. Since neurological symptoms of electrolyte disorders are generally functional rather than structural, the neurologic manifestations of electrolyte disturbances are typically reversible. The neurologic manifestations of serum sodium, potassium, calcium, and magnesium disturbances are reviewed.

Gastric cytoprotective anti-ulcerogenic actions of hydroxychalcones in rats.

PubMed

Yamamoto, K; Kakegawa, H; Ueda, H; Matsumoto, H; Sudo, T; Miki, T; Satoh, T

1992-10-01

The preventive effects of hydroxychalcone derivatives on ulcer formation induced by severe necrotizing agents such as 60% ethanol in 150 mM HCl (HCl-ethanol) and 0.2 N NaOH in rats were examined. Among the compounds tested, 2',4'-dihydroxychalcone gave the strongest activity in both experimental models and protected the gastric mucosa from the insult of either necrotizing agent at oral doses ranging from 1 to 10 mg/kg, as evidenced by a dose-related reduction in the ulcer index. The mucosal protective activity of 2',4'-dihydroxychalcone was not affected by pretreatment with indomethacin (5 mg/kg, s.c.). To investigate the detailed mechanism of the mucosal protective action of 2',4'-dihydroxychalcone, its inhibitory effects on the decrease in the hexosamine content from the gastric mucus induced by HCl-ethanol were studied by using it in combination with a dye, Alcian blue. As a result, 2',4'-dihydroxychalcone at an oral dose of 10 mg/kg inhibited the decrease in the dye-recovery from the gastric mucus induced by HCl-ethanol. PGE2 at an oral dose of 0.1 mg/kg exhibited a similar action. These results established that 2',4'-dihydroxychalcone is a potent cytoprotective agent similar to PGE2 effectively preventing gastric ulcer formation induced by strong necrotizing agents and seems to suggest that this compound protects the stomach against its own peptic secretions by reinforcement of gastric resistances. In fact, 2',4'-dihydroxychalcone prevented ulcer formation induced by water-immersion stress in rats and also showed a marked enhancement of the healing of acetic acid-induced gastric ulcers in rats.

Multiparametric evaluation of the cytoprotective effect of the Mangifera indica L. stem bark extract and mangiferin in HepG2 cells.

PubMed

Tolosa, Laia; Rodeiro, Idania; Donato, M Teresa; Herrera, José A; Delgado, René; Castell, José V; Gómez-Lechón, M José

2013-07-01

Mango (Mangifera indica L.) stem bark extract (MSBE) is a natural product with biological properties and mangiferin is the major component. This paper reported the evaluation of the protective effects of MSBE and mangiferin against the toxicity induced in HepG2 cells by tert-butyl hydroperoxide or amiodarone. Nuclear morphology, cell viability, intracellular calcium concentration and reactive oxygen species (ROS) production were measured by using a high-content screening multiparametric assay. MSBE and mangiferin produced no toxicity below 500 mg/ml doses. A marked recovery in cell viability, which was reduced by the toxicants, was observed in cells pre-exposed to MSBE or mangiferin at 5-100 mg/ml doses. We also explored the possible interaction of both products over P-glycoprotein (P-gp). MSBE and mangiferin above 100 mg/ml inhibited the activity of P-gp in HepG2 cells. MSBE and mangiferin showed cytoprotective effects of against oxidative damage and mitochondrial toxicity induced by xenobiotics to human hepatic cells but it seemed that other constituents of the extract could contribute to MSBE protective properties. In addition, the drug efflux should be taken into account because of the inhibition of the P-gp function observed in those cells exposed to both natural products. © 2013 Royal Pharmaceutical Society.

Characterizing the cytoprotective activity of Sarracenia purpurea L., a medicinal plant that inhibits glucotoxicity in PC12 cells.

PubMed

Harris, Cory S; Asim, Muhammad; Saleem, Ammar; Haddad, Pierre S; Arnason, John T; Bennett, Steffany A L

2012-12-05

The purple pitcher plant, Sarracenia purpurea L., is a widely distributed species in North America with a history of use as both a marketed pain therapy and a traditional medicine in many aboriginal communities. Among the Cree of Eeyou Istchee in northern Québec, the plant is employed to treat symptoms of diabetes and the leaf extract demonstrates multiple anti-diabetic activities including cytoprotection in an in vitro model of diabetic neuropathy. The current study aimed to further investigate this activity by identifying the plant parts and secondary metabolites that contribute to these cytoprotective effects. Ethanolic extracts of S. purpurea leaves and roots were separately administered to PC12 cells exposed to glucose toxicity with subsequent assessment by two cell viability assays. Assay-guided fractionation of the active extract and fractions was then conducted to identify active principles. Using high pressure liquid chromatography together with mass spectrometry, the presence of identified actives in both leaf and root extracts were determined. The leaf extract, but not that of the root, prevented glucose-mediated cell loss in a concentration-dependent manner. Several fractions elicited protective effects, indicative of multiple active metabolites, and, following subfractionation of the polar fraction, hyperoside (quercetin-3-O-galactoside) and morroniside were isolated as active constituents. Phytochemical analysis confirmed the presence of hyperoside in the leaf but not root extract and, although morroniside was detected in both organs, its concentration was seven times higher in the leaf. Our results not only support further study into the therapeutic potential and safety of S. purpurea as an alternative and complementary treatment for diabetic complications associated with glucose toxicity but also identify active principles that can be used for purposes of standardization and quality control.

Characterizing the cytoprotective activity of Sarracenia purpurea L., a medicinal plant that inhibits glucotoxicity in PC12 cells

PubMed Central

2012-01-01

Background The purple pitcher plant, Sarracenia purpurea L., is a widely distributed species in North America with a history of use as both a marketed pain therapy and a traditional medicine in many aboriginal communities. Among the Cree of Eeyou Istchee in northern Québec, the plant is employed to treat symptoms of diabetes and the leaf extract demonstrates multiple anti-diabetic activities including cytoprotection in an in vitro model of diabetic neuropathy. The current study aimed to further investigate this activity by identifying the plant parts and secondary metabolites that contribute to these cytoprotective effects. Methods Ethanolic extracts of S. purpurea leaves and roots were separately administered to PC12 cells exposed to glucose toxicity with subsequent assessment by two cell viability assays. Assay-guided fractionation of the active extract and fractions was then conducted to identify active principles. Using high pressure liquid chromatography together with mass spectrometry, the presence of identified actives in both leaf and root extracts were determined. Results The leaf extract, but not that of the root, prevented glucose-mediated cell loss in a concentration-dependent manner. Several fractions elicited protective effects, indicative of multiple active metabolites, and, following subfractionation of the polar fraction, hyperoside (quercetin-3-O-galactoside) and morroniside were isolated as active constituents. Phytochemical analysis confirmed the presence of hyperoside in the leaf but not root extract and, although morroniside was detected in both organs, its concentration was seven times higher in the leaf. Conclusion Our results not only support further study into the therapeutic potential and safety of S. purpurea as an alternative and complementary treatment for diabetic complications associated with glucose toxicity but also identify active principles that can be used for purposes of standardization and quality control. PMID:23216659

Signaling pathways underpinning the manifestations of ionizing radiation-induced bystander effects.

PubMed

Hamada, Nobuyuki; Maeda, Munetoshi; Otsuka, Kensuke; Tomita, Masanori

2011-06-01

For nearly a century, ionizing radiation has been indispensable to medical diagnosis. Furthermore, various types of electromagnetic and particulate radiation have also been used in cancer therapy. However, the biological mechanism of radiation action remains incompletely understood. In this regard, a rapidly growing body of experimental evidence indicates that radiation exposure induces biological effects in cells whose nucleus has not been irradiated. This phenomenon termed the 'non-targeted effects' challenges the long-held tenet that radiation traversal through the cell nucleus is a prerequisite to elicit genetic damage and biological responses. The non-targeted effects include biological effects in cytoplasm-irradiated cells, bystander effects that arise in non-irradiated cells having received signals from irradiated cells, and genomic instability occurring in the progeny of irradiated cells. Such non-targeted responses are interrelated, and the bystander effect is further related with an adaptive response that manifests itself as the attenuated stressful biological effects of acute high-dose irradiation in cells that have been pre-exposed to low-dose or low-dose-rate radiation. This paper reviews the current body of knowledge about the bystander effect with emphasis on experimental approaches, in vitro and in vivo manifestations, radiation quality dependence, temporal and spatial dependence, proposed mechanisms, and clinical implications. Relations of bystander responses with the effects in cytoplasm-irradiated cells, genomic instability and adaptive response will also be briefly discussed.

A novel shogaol analog suppresses cancer cell invasion and inflammation, and displays cytoprotective effects through modulation of NF-κB and Nrf2-Keap1 signaling pathways.

PubMed

Gan, Fei-Fei; Ling, Hui; Ang, Xiaohui; Reddy, Shridhivya A; Lee, Stephanie S-H; Yang, Hong; Tan, Sock-Hoon; Hayes, John D; Chui, Wai-Keung; Chew, Eng-Hui

2013-11-01

Natural compounds containing vanilloid and Michael acceptor moieties appear to possess anti-cancer and chemopreventive properties. The ginger constituent shogaol represents one such compound. In this study, the anti-cancer potential of a synthetic novel shogaol analog 3-phenyl-3-shogaol (3-Ph-3-SG) was assessed by evaluating its effects on signaling pathways. At non-toxic concentrations, 3-Ph-3-SG suppressed cancer cell invasion in MDA-MB-231 and MCF-7 breast carcinoma cells through inhibition of PMA-activated MMP-9 expression. At similar concentrations, 3-Ph-3-SG reduced expression of the inflammatory mediators nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and prostanglandin-E2 (PGE2) in RAW 264.7 macrophage-like cells. Inhibition of cancer cell invasion and inflammation by 3-Ph-3-SG were mediated through suppression of the nuclear factor-kappaB (NF-κB) signaling pathway. The 3-Ph-3-SG also demonstrated cytoprotective effects by inducing the antioxidant response element (ARE)-driven genes NAD(P)H quinone oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1). Cytoprotection by 3-Ph-3-SG was achieved at least partly through modification of cysteine residues in the E3 ubiquitin ligase substrate adaptor Kelch-like ECH-associated protein 1 (Keap1), which resulted in accumulation of transcription factor NF-E2 p45-related factor 2 (Nrf2). The activities of 3-Ph-3-SG were comparable to those of 6-shogaol, the most abundant naturally-occurring shogaol, and stronger than those of 4-hydroxyl-null deshydroxy-3-phenyl-3-shogaol, which attested the importance of the 4-hydroxy substituent in the vanilloid moiety for bioactivity. In summary, 3-Ph-3-SG is shown to possess activities that modulate stress-associated pathways relevant to multiple steps in carcinogenesis. Therefore, it warrants further investigation of this compound as a promising candidate for use in chemotherapeutic and chemopreventive strategies. © 2013.

A genetic screen in Drosophila reveals novel cytoprotective functions of the autophagy-lysosome pathway.

PubMed

Arsham, Andrew M; Neufeld, Thomas P

2009-06-29

The highly conserved autophagy-lysosome pathway is the primary mechanism for breakdown and recycling of macromolecular and organellar cargo in the eukaryotic cell. Autophagy has recently been implicated in protection against cancer, neurodegeneration, and infection, and interest is increasing in additional roles of autophagy in human health, disease, and aging. To search for novel cytoprotective features of this pathway, we carried out a genetic mosaic screen for mutations causing increased lysosomal and/or autophagic activity in the Drosophila melanogaster larval fat body. By combining Drosophila genetics with live-cell imaging of the fluorescent dye LysoTracker Red and fixed-cell imaging of autophagy-specific fluorescent protein markers, the screen was designed to identify essential metazoan genes whose disruption causes increased flux through the autophagy-lysosome pathway. The screen identified a large number of genes associated with the protein synthesis and ER-secretory pathways (e.g. aminoacyl tRNA synthetases, Oligosaccharyl transferase, Sec61alpha), and with mitochondrial function and dynamics (e.g. Rieske iron-sulfur protein, Dynamin-related protein 1). We also observed that increased lysosomal and autophagic activity were consistently associated with decreased cell size. Our work demonstrates that disruption of the synthesis, transport, folding, or glycosylation of ER-targeted proteins at any of multiple steps leads to autophagy induction. In addition to illuminating cytoprotective features of autophagy in response to cellular damage, this screen establishes a genetic methodology for investigating cell biological phenotypes in live cells, in the context of viable wild type organisms.

Cholinergic and cytoprotective signaling cascades mediate the mitigative effect of erythropoietin on acute radiation syndrome.

PubMed

Galal, Shereen Mohamed; Abdel-Rafei, Mohamed Khairy; Hasan, Hesham Farouk

2018-05-01

The present investigation aimed to evaluate the radiomitigative efficacy of the recombinant human erythropoietin (EPO) against acute radiation syndrome (ARS) in a rat model. Rats were irradiated with a single sublethal dose of γ-radiation (7 Gy; total body irradiation; TBI) on the 1st day of experimental course, then received EPO (5000 IU/kg; i.p.) 24 h after irradiation, and rats were observed for 30 days of survival analysis. Administration of EPO improved 30-day survival, alleviated TBI-induced myelosuppression and pancytopenia, by augmenting lymphocytes and other white blood cells in the peripheral blood of rats, while bone marrow and spleen cellularity were restored. EPO post-exposure treatment alleviated hepatotoxicity biomarkers and restored splenic function. EPO abrogated radiation-induced oxidative stress through the upregulation of the cholinergic anti-inflammatory nicotinic acetylcholine receptor (α-7-nAChR) and the pro-survival Janus kinase-2 and signal transducers and activators of transcription JAK-2/STAT-3 signaling mediated via enhancing nuclear factor erythroid-2 related factor-2 (Nrf-2) cytoprotective machinery in liver and spleen of irradiated rats. Moreover, EPO treatment prevented hepatic and splenic apoptosis. The present study establishes the implication of α-7-nAChR-JAK-2/STAT-3-Nrf-2 signaling cascade in the radiomitigative potential of EPO against ARS.

Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy

PubMed Central

García, Isabel Mercedes; Altamirano, Liliana; Mazzei, Luciana; Fornés, Miguel; Molina, Marisa Nile; Ferder, León

2012-01-01

Vitamin D slows the progression of chronic kidney disease. Furthermore, activators of vitamin D receptors (VDR) have suppressant effects on the renin-angiotensin system, as well as anti-inflammatory and antifibrotic actions. This study aimed to evaluate the cytoprotective effects of paricalcitol, a VDR activator, at the mitochondrial level using an obstructive nephropathy model [unilateral ureteral obstruction (UUO)]. Rats subjected to UUO and controls were treated daily with vehicle or paricalcitol. The control group underwent a sham surgery. The treatment was done for 15 days (30 ng/kg). The following were determined: biochemical parameters; fibrosis; apoptosis; mitochondrial morphology; VDR, AT1 receptor, and NADPH oxidase 4 expression; and NADPH oxidase activity (in total and in mitochondrial fractions from the renal cortex). VDR activation prevented fibrosis (20 ± 5 vs. 60 ± 10%) and the number of TUNEL-positive apoptotic cells (10 ± 3 vs. 25 ± 4) in UUO. Biochemical, histological, and molecular studies suggest mitochondrial injury. Electron microscopy revealed in UUO electronically luminous material in the nucleus. Some mitochondria were increased in size and contained dilated crests and larger than normal spaces in their interiors. These changes were not present with paricalcitol treatment. Additionally, high AT1-receptor mRNA and NADPH activity was reverted in mitochondrial fractions from obstructed paricalcitol-treated animals (0.58 ± 0.06 vs. 0.95 ± 0.05 relative densitometry units and 9,000 ± 800 vs. 15,000 ± 1,000 relative fluorescence units·μg protein−1·min−1, respectively). These changes were consistent with an improvement in VDR expression (0.75 ± 0.05 vs. 0.35 ± 0.04 relative densitometry units). These results suggest that paricalcitol confers a protective effect and reveal, as well, a possible AT1 receptor-dependent protective effect that occurs at the mitochondrial level. PMID:22492946

Different effects of cytoprotective drugs on ethanol- and aspirin-induced gastric mucosal injury in pylorus-ligated rats

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

Takeuchi, K.; Nishiwaki, H.; Niida, H.

In anesthetized rats oral administration (2 ml) of both ethanol (50% in 150 mM HCl) and aspirin (80 mM in 150 mM HCl) produced bandlike lesions in the stomach, while more generalized lesions occurred in the pylorus-ligated stomach when the irritant was given intragastrically through the fistula prepared in the rumen and the mucosal folds were removed by stomach distension. The bandlike lesions induced in the intact stomach by both irritants were significantly and dose-dependently prevented by 16,16-dimethyl PGE2 (dmPGE2: 3 and 10 micrograms/kg, subcutaneously), cysteamine (30 and 100 mg/kg, subcutaneously) or timoprazole (10 and 30 mg/kg, per os) atmore » the doses which significantly inhibited gastric motility. In the pylorus-ligated stomach, however, neither of these agents showed any protection against the generalized lesions induced by ethanol, but such lesions caused by aspirin were significantly prevented only by dmPGE2. These agents also showed similar effects against the reduction of transmucosal PD in the pylorus-ligated stomach exposed to ethanol and aspirin. These results suggest that (1) the formation of bandlike lesions caused by ethanol and aspirin depends on the presence of mucosal folds and may be prevented by the agents that inhibit gastric motility, (2) the pathogenesis of the lesions induced by aspirin and ethanol may be different in the pylorus-ligated stomach, and (3) dmPGE2 has a unique protective ability that is not shared by usual cytoprotective agents.« less

In Vitro Evaluation of the Antioxidant, Cytoprotective, and Antimicrobial Properties of Essential Oil from Pistacia vera L. Variety Bronte Hull

PubMed Central

Smeriglio, Antonella; Denaro, Marcella; Barreca, Davide; Calderaro, Antonella; Bisignano, Carlo; Ginestra, Giovanna; Bellocco, Ersilia; Trombetta, Domenico

2017-01-01

Although the chemical composition and biological properties of some species of the genus Pistacia has been investigated, studies on hull essential oil of Pistacia vera L. variety Bronte (HEO) are currently lacking. In this work, we have carried out an in-depth phytochemical profile elucidation by Gas Chromatography-Mass Spectrometry (GC-MS) analysis, and an evaluation of antioxidant scavenging properties of HEO, using several different in vitro methods, checking also its cytoprotective potential on lymphocytes treated with tert-butyl hydroperoxide. Moreover, the antimicrobial activity against Gram-positive and Gram-negative strains, both American Type Culture Collection (ATCC) and clinical isolates, was also investigated. GC-MS analysis highlighted the richness of this complex matrix, with the identification of 40 derivatives. The major components identified were 4-Carene (31.743%), α-Pinene (23.584%), d-Limonene (8.002%), and 3-Carene (7.731%). The HEO showed a strong iron chelating activity and was found to be markedly active against hydroxyl radical, while scarce effects were found against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. Moreover, pre-treatment with HEO was observed to significantly increase the cell viability, decreasing the lactate dehydrogenase (LDH) release. HEO was bactericidal against all the tested strains at the concentration of 7.11 mg/mL, with the exception of Pseudomonas aeruginosa ATCC 9027. The obtained results demonstrate the strong free-radical scavenging activity of HEO along with remarkable cytoprotective and antimicrobial properties. PMID:28587291

In Vitro Evaluation of the Antioxidant, Cytoprotective, and Antimicrobial Properties of Essential Oil from Pistacia vera L. Variety Bronte Hull.

PubMed

Smeriglio, Antonella; Denaro, Marcella; Barreca, Davide; Calderaro, Antonella; Bisignano, Carlo; Ginestra, Giovanna; Bellocco, Ersilia; Trombetta, Domenico

2017-06-06

Although the chemical composition and biological properties of some species of the genus Pistacia has been investigated, studies on hull essential oil of Pistacia vera L. variety Bronte (HEO) are currently lacking. In this work, we have carried out an in-depth phytochemical profile elucidation by Gas Chromatography-Mass Spectrometry (GC-MS) analysis, and an evaluation of antioxidant scavenging properties of HEO, using several different in vitro methods, checking also its cytoprotective potential on lymphocytes treated with tert-butyl hydroperoxide. Moreover, the antimicrobial activity against Gram-positive and Gram-negative strains, both American Type Culture Collection (ATCC) and clinical isolates, was also investigated. GC-MS analysis highlighted the richness of this complex matrix, with the identification of 40 derivatives. The major components identified were 4-Carene (31.743%), α-Pinene (23.584%), d-Limonene (8.002%), and 3-Carene (7.731%). The HEO showed a strong iron chelating activity and was found to be markedly active against hydroxyl radical, while scarce effects were found against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. Moreover, pre-treatment with HEO was observed to significantly increase the cell viability, decreasing the lactate dehydrogenase (LDH) release. HEO was bactericidal against all the tested strains at the concentration of 7.11 mg/mL, with the exception of Pseudomonas aeruginosa ATCC 9027. The obtained results demonstrate the strong free-radical scavenging activity of HEO along with remarkable cytoprotective and antimicrobial properties.

Modulation of transglutaminase 2 activity in H9c2 cells by PKC and PKA signalling: a role for transglutaminase 2 in cytoprotection

PubMed Central

Almami, Ibtesam; Dickenson, John M; Hargreaves, Alan J; Bonner, Philip L R

2014-01-01

BACKGROUND AND PURPOSE Tissue transglutaminase (TG2) has been shown to mediate cell survival in many cell types. In this study, we investigated whether the role of TG2 in cytoprotection was mediated by the activation of PKA and PKC in cardiomyocyte-like H9c2 cells. EXPERIMENTAL APPROACH H9c2 cells were extracted following stimulation with phorbol-12-myristate-13-acetate (PMA) and forskolin. Transglutaminase activity was determined using an amine incorporating and a protein crosslinking assay. The presence of TG isoforms (TG1, 2, 3) was determined using Western blot analysis. The role of TG2 in PMA- and forskolin-induced cytoprotection was investigated by monitoring H2O2-induced oxidative stress in H9c2 cells. KEY RESULTS Western blotting showed TG2 >> TG1 protein expression but no detectable TG3. The amine incorporating activity of TG2 in H9c2 cells increased in a time and concentration-dependent manner following stimulation with PMA and forskolin. PMA and forskolin-induced TG2 activity was blocked by PKC (Ro 31-8220) and PKA (KT 5720 and Rp-8-Cl-cAMPS) inhibitors respectively. The PMA- and forskolin-induced increases in TG2 activity were attenuated by the TG2 inhibitors Z-DON and R283. Immunocytochemistry revealed TG2-mediated biotin-X-cadaverine incorporation into proteins and proteomic analysis identified known (β-tubulin) and novel (α-actinin) protein substrates for TG2. Pretreatment with PMA and forskolin reversed H2O2-induced decrease in MTT reduction and release of LDH. TG2 inhibitors R283 and Z-DON blocked PMA- and forskolin-induced cytoprotection. CONCLUSIONS AND IMPLICATIONS TG2 activity was stimulated via PKA- and PKC-dependent signalling pathways in H9c2 cells These results suggest a role for TG2 in cytoprotection induced by these kinases. PMID:24821315

The chalcone compound isosalipurposide (ISPP) exerts a cytoprotective effect against oxidative injury via Nrf2 activation

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

Han, Jae Yun; Cho, Seung Sik; Yang, Ji Hye

2015-08-15

The chalcone compound isosalipurposide (ISPP) has been successfully isolated from the native Korean plant species Corylopsis coreana Uyeki (Korean winter hazel). However, the therapeutic efficacy of ISPP remains poorly understood. This study investigated whether ISPP has the capacity to activate NF-E2-related factor (Nrf2)-antioxidant response element (ARE) signaling and induce its target gene expression, and to determined the protective role of ISPP against oxidative injury of hepatocytes. In HepG2 cells, nuclear translocation of Nrf2 is augmented by ISPP treatment. Consistently, ISPP increased ARE reporter gene activity and the protein levels of glutamate cysteine ligase (GCL) and hemeoxygenase (HO-1), resulting in increasedmore » intracellular glutathione levels. Cells pretreated with ISPP were rescued from tert-butylhydroperoxide-induced reactive oxygen species (ROS) production and glutathione depletion and consequently, apoptotic cell death. Moreover, ISPP ameliorated the mitochondrial dysfunction and apoptosis induced by rotenone which is an inhibitor of complex 1 of the mitochondrial respiratory chain. The specific role of Nrf2 activation by ISPP was demonstrated using an ARE-deletion mutant plasmid and Nrf2-knockout cells. Finally, we observed that extracellular signal-regulated kinase (ERK) and AMP-activated protein kinase (AMPK), but not protein kinase C (PKC)-δ or other mitogen-activated protein kinases (MAPKs), are involved in the activation of Nrf2 by ISPP. Taken together, our results demonstrate that ISPP has a cytoprotective effect against oxidative damage mediated through Nrf2 activation and induction of its target gene expression in hepatocytes. - Highlights: • We investigated the effect of ISPP on Nrf2 activation. • ISPP increased Nrf2 activity and its target gene expression. • ISPP inhibited the mitochondrial dysfunction and ROS production. • Nrf2 activation by ISPP is dependent on ERK1/2 and AMPK phosphorylation. • ISPP may be a

Antioxidant and gastric cytoprotective prostaglandins properties of Cassia sieberiana roots bark extract as an anti-ulcerogenic agent.

PubMed

Nartey, Edmund T; Ofosuhene, Mark; Kudzi, William; Agbale, Caleb M

2012-05-20

Cassia sieberiana is a savannah tree with a wide phytotherapeutic application including the use of its roots in the management of various stomach disorders including gastric ulcer, stomach pains and indigestion. The aim of the study is to evaluate the antioxidant, gastric cytoprotective prostaglandins, secretory phospholipase A2, phytochemical and acute toxicity properties of Cassia sieberiana roots bark extract in a bid to justify its phytotherapeutic applications in gastric ulcer. Antioxidant and radical scavenging activities of the roots bark extract of Cassia sieberiana were assayed. Serum secretory phospholipase A2 (sPLA2) concentration and activity and the formation of gastric mucosal prostaglandins E2 (PGE2) and I2 (PGI2) were also assessed. Comparisons between means were performed using analysis of variance (ANOVA) followed by Students Standard Newman-Keuls post hoc analysis to determine statistical significance. P < 0.05 was considered significant. The extract was found to possess significant ferric reducing antioxidant power and can scavenge hydroxyl radicals. The extract also possesses DPPH scavenging activity, can chelate ferrous ion and a dose-dependent protective effect against lipid peroxidation and free radical generation. Prostaglandin studies showed that the roots bark extract dose dependently increased gastric mucosal PGE2 and PGI2 levels and also decreased serum sPLA2 activity. Phytochemical analyses suggest that the roots extract contains polyhydroxyl/phenolic substances. Acute toxicity test showed no sign of toxicity up to a dose level of 2000 mg/kg body weight p.o. C. sieberiana roots extract possesses significant antioxidant and gastric cytoprotective prostaglandin properties as well as serum secretory phospholipase A2 inhibitory activity which could be due to its content of polyhydroxy and/or phenolic substances. This may justify its use as an anti-ulcerogenic agent in traditional medicine in West Africa.

Clinical manifestations of scrub typhus.

PubMed

Rajapakse, Senaka; Weeratunga, Praveen; Sivayoganathan, Sriharan; Fernando, Sumadhya Deepika

2017-02-01

The mite-borne rickettsial zoonosis scrub typhus is widely prevalent in parts of Southeast and Far East Asia, and northern Australia. The disease is an acute febrile illness, associated with rash and often an eschar, which responds dramatically to treatment with antibiotics. In some cases it results in a serious illness leading to multiple organ involvement and death. The disease manifestations are thought to result from a systemic vasculitis, caused by both direct effects of the organisms as well as an exaggerated immune response, although little is understood about its pathogenesis. A wide spectrum of clinical manifestations, affecting nearly every organ system, have been described with scrub typhus. Some of these manifestations are serious and life threatening. In this systematic review, we summarise the typical and atypical manifestations of scrub typhus reported in the literature. Awareness of these unusual manifestations will hopefully guide clinicians towards diagnosing the condition early, and initiating early appropriate antibiotics and other supportive measures. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Enhancement of the depigmenting effect of hydroquinone and 4-hydroxyanisole by all-trans-retinoic acid (tretinoin): the impairment of glutathione-dependent cytoprotection?

PubMed

Kasraee, Behrooz; Handjani, Farhad; Aslani, Fatemeh S

2003-01-01

Many of the well-known depigmenting agents such as hydroquinone and 4-hydroxyanisole are, in fact, melanocytotoxic chemicals which are oxidized in melanocytes to produce highly toxic compounds such as quinones. These cytotoxic compounds are responsible for the destruction of pigment cells, which results in skin depigmentation. However, cells are capable of protecting themselves against cytotoxic agents by intracellular glutathione (GSH). This protection takes place under the enzymatic action of the detoxification enzyme glutathione S-transferase (GST), which is responsible for the conjugation of toxic species to GSH. The depigmenting effect of hydroquinone is shown to be potentiated by buthionine sulfoximine (BSO) and cystamine as the result of the reduction of intracellular levels of GSH by these two agents. Additionally, BSO and cystamine are shown to inhibit the activity of GST. The combination of all-trans-retinoic acid (tretinoin, TRA) with hydroquinone or 4-hydroxyanisole is also known to produce synergetic skin depigmentation. TRA serves as a potent inhibitor of mammalian GSTs and is known to make cells more susceptible to the cytotoxic effect of chemicals by inhibiting the activity of this enzyme. This agent is also shown to reduce the level of intracellular GSH in certain cells. We have proposed that the mechanism of action of TRA to synergistically enhance the melanocytotoxic effect of chemicals involves the inhibition of GST and the impairment of glutathione-dependent cytoprotection against melanocytotoxic agents. Copyright 2003 S. Karger AG, Basel

10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress

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

Furumoto, Hidehiro; Nanthirudjanar, Tharnath; Kume, Toshiaki

Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H:quinone oxidoreductasemore » 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. - Highlights: • We evaluated the effect of modified fatty acids generated by Lactobacillus plantarum. • 10-Oxo-trans-11-ocatadecenoic acid (KetoC) protected cells from oxidative stress. • KetoC activated the Nrf2-ARE pathway to promote antioxidative gene expression. • KetoC promoted the expression of antioxidative enzymes in mice organs. • The cytoprotective effect of KetoC was because of α,β-unsaturated carbonyl moiety.« less

Oral manifestations of inflammatory bowel disease.

PubMed

Mortada, I; Leone, A; Gerges Geagea, A; Mortada, R; Matar, C; Rizzo, M; Hajj Hussein, I; Massaad-Massade, L; Jurjus, A

2017-01-01

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, have important extraintestinal manifestations, notably in the oral cavity. These oral manifestations can constitute important clinical clues in the diagnosis and management of IBD, and include changes at the immune and bacterial levels. Aphthous ulcers, pyostomatitis vegetans, cobblestoning and gingivitis are important oral findings frequently observed in IBD patients. Their presentations vary considerably and might be well diagnosed and distinguished from other oral lesions. Infections, drug side effects, deficiencies in some nutrients and many other diseases involved with oral manifestations should also be taken into account. This article discusses the most recent findings on the oral manifestations of IBD with a focus on bacterial modulations and immune changes. It also includes an overview on options for management of the oral lesions of IBD.

Vitamin E confers cytoprotective effects on cardiomyocytes under conditions of heat stress by increasing the expression of metallothionein.

PubMed

Wang, Xiaowu; Dong, Wenpeng; Yuan, Binbin; Yang, Yongchao; Yang, Dongpeng; Lin, Xi; Chen, Changfu; Zhang, Weida

2016-05-01

Heat stress (HS) is commonly used to refer to the heat load that an individual is subjected to due to either metabolic heat, or environmental factors, including high temperatures and high humidity levels. HS has been reported to affect and even damage the functioning of various organs; overexposure to high temperatures and high humidity may lead to accidental deaths. It has been suggested that the cardiovascular system is primarily targeted by exposure to HS conditions; the HS-induced dysfunction of cardiomyocytes, which is characterized by mitochondrial dysfunction, may result in the development of cardiovascular diseases. The excessive production of reactive oxygen species (ROS) also participates in mitochondrial dysfunction. However, effective methods for the prevention and treatment of mitochondrial and cardiovascular dysfunction induced by exposure to HS are lacking. In the present study, we hypothesized that vitamin E (VE), an antioxidant, is capable of preventing oxidative stress and mitochondrial injury in cardiomyocytes induced by exposure to HS. The results revealed that pre‑treatment with VE increased the expression of metallothionein (MT), which has previously been reported to confer cytoprotective effects, particularly on the cardiovascular system. Pre-treatment with VE restored mitochondrial function in cardiomyocytes under conditions of HS by increasing the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM), and by increasing adenosine triphosphate (ATP) levels. Furthermore, pre-treatment with VE decreased the production of ROS, which was induced by exposure to HS and thus exerted antioxidant effects. In addition, pre-treatment with VE attenuated oxidative stress induced by exposure to HS, as demonstrated by the increased levels of antioxidant enzymes [superoxide dismutase (SOD) and glutathione (GSH)], and by the decreased levels

Erythrocytes and cell line-based assays to evaluate the cytoprotective activity of antioxidant components obtained from natural sources.

PubMed

Botta, Albert; Martínez, Verónica; Mitjans, Montserrat; Balboa, Elena; Conde, Enma; Vinardell, M Pilar

2014-02-01

Oxidative stress can damage cellular components including DNA, proteins or lipids, and may cause several skin diseases. To protect from this damage and addressing consumer's appeal to natural products, antioxidants obtained from algal and vegetal extracts are being proposed as antioxidants to be incorporated into formulations. Thus, the development of reliable, quick and economic in vitro methods to study the cytoactivity of these products is a meaningful requirement. A combination of erythrocyte and cell line-based assays was performed on two extracts from Sargassum muticum, one from Ulva lactuca, and one from Castanea sativa. Antioxidant properties were assessed in erythrocytes by the TBARS and AAPH assays, and cytotoxicity and antioxidant cytoprotection were assessed in HaCaT and 3T3 cells by the MTT assay. The extracts showed no antioxidant activity on the TBARS assay, whereas their antioxidant capacity in the AAPH assay was demonstrated. On the cytotoxicity assays, extracts showed low toxicity, with IC50 values higher than 200μg/mL. C. sativa extract showed the most favourable antioxidant properties on the antioxidant cytoprotection assays; while S. muticum and U. lactuca extracts showed a slight antioxidant activity. This battery of methods was useful to characterise the biological antioxidant properties of these natural extracts. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hazardous Waste Electronic Manifest System (e-Manifest) Advisory Board

EPA Pesticide Factsheets

This page is all about the e-manifest Advisory board, formed under the Federal Advisory Committee Act, and part of the EPA's e-manifest development process. Here you can learn about the members and their meetings.

e-Manifest

EPA Pesticide Factsheets

This is the primary hub for those seeking information about the e-Manifest system, its advisory board, and its development. Once the system is complete this area will serve as the portal into the e-Manifest system from EPA webpages.

VEGF-A165b Is Cytoprotective and Antiangiogenic in the Retina

PubMed Central

Magnussen, Anette L.; Rennel, Emma S.; Hua, Jing; Bevan, Heather S.; Long, Nicholas Beazley; Lehrling, Christina; Gammons, Melissa; Floege, Juergen; Harper, Steven J.; Agostini, Hansjürgen T.; Bates, David O.; Churchill, Amanda J.

2010-01-01

Purpose. A number of key ocular diseases, including diabetic retinopathy and age-related macular degeneration, are characterized by localized areas of epithelial or endothelial damage, which can ultimately result in the growth of fragile new blood vessels, vitreous hemorrhage, and retinal detachment. VEGF-A165, the principal neovascular agent in ocular angiogenic conditions, is formed by proximal splice site selection in its terminal exon 8. Alternative splicing of this exon results in an antiangiogenic isoform, VEGF-A165b, which is downregulated in diabetic retinopathy. Here the authors investigate the antiangiogenic activity of VEGF165b and its effect on retinal epithelial and endothelial cell survival. Methods. VEGF-A165b was injected intraocularly in a mouse model of retinal neovascularization (oxygen-induced retinopathy [OIR]). Cytotoxicity and cell migration assays were used to determine the effect of VEGF-A165b. Results. VEGF-A165b dose dependently inhibited angiogenesis (IC50, 12.6 pg/eye) and retinal endothelial migration induced by 1 nM VEGF-A165 across monolayers in culture (IC50, 1 nM). However, it also acts as a survival factor for endothelial cells and retinal epithelial cells through VEGFR2 and can stimulate downstream signaling. Furthermore, VEGF-A165b injection, while inhibiting neovascular proliferation in the eye, reduced the ischemic insult in OIR (IC50, 2.6 pg/eye). Unlike bevacizumab, pegaptanib did not interact directly with VEGF-A165b. Conclusions. The survival effects of VEGF-A165b signaling can protect the retina from ischemic damage. These results suggest that VEGF-A165b may be a useful therapeutic agent in ischemia-induced angiogenesis and a cytoprotective agent for retinal pigment epithelial cells. PMID:20237249

Learn about the Hazardous Waste Electronic Manifest System (e-Manifest)

EPA Pesticide Factsheets

This webpage provides information on EPA's work toward developing a hazardous waste electronic manifest system. Information on the Hazardous Waste Electronic Manifest Establishment Act, progress on the project and frequent questions are available.

The Cytoprotective Effects of E-α-(4-Methoxyphenyl)-2’,3,4,4'-Tetramethoxychalcone (E-α-p-OMe-C6H4-TMC)—A Novel and Non-Cytotoxic HO-1 Inducer

PubMed Central

Kaufmann, Kai B.; Al-Rifai, Nafisah; Ulbrich, Felix; Schallner, Nils; Rücker, Hannelore; Enzinger, Monika; Petkes, Hermina; Pitzl, Sebastian

2015-01-01

Cell protection against different noxious stimuli like oxidative stress or chemical toxins plays a central role in the treatment of many diseases. The inducible heme oxygenase isoform, heme oxygenase-1 (HO-1), is known to protect cells against a variety of harmful conditions including apoptosis. Because a number of medium strong electrophiles from a series of α-X-substituted 2’,3,4,4’-tetramethoxychalcones (α-X-TMCs, X = H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH) had proven to activate Nrf2 resulting in HO-1 induction and inhibit NF-κB downstream target genes, their protective effect against staurosporine induced apoptosis and reactive oxygen species (ROS) production was investigated. RAW264.7 macrophages treated with 19 different chalcones (15 α-X-TMCs, chalcone, 2’-hydroxychalcone, calythropsin and 2’-hydroxy-3,4,4’-trimethoxychalcone) prior to staurosporine treatment were analyzed for apoptosis and ROS production, as well as HO-1 protein expression and enzyme activity. Additionally, Nrf2 and NF-κB activity was assessed. We found that amongst all tested chalcones only E-α-(4-methoxyphenyl)-2’,3,4,4'-tetramethoxychalcone (E-α-p-OMe-C6H4-TMC) demonstrated a distinct, statistically significant antiapoptotic effect in a dose dependent manner, showing no toxic effects, while its double bond isomer Z-α-p-OMe-C6H4-TMC displayed no significant activity. Also, E-α-p-OMe-C6H4-TMC induced HO-1 protein expression and increased HO-1 activity, whilst inhibition of HO-1 by SnPP-IX abolished its antiapoptotic effect. The only weakly electrophilic chalcone E-α-p-OMe-C6H4-TMC reduced the staurosporine triggered formation of ROS, while inducing the translocation of Nrf2 into the nucleus. Furthermore, staurosporine induced NF-κB activity was attenuated following E-α-p-OMe-C6H4-TMC treatment. Overall, E-α-p-OMe-C6H4-TMC demonstrated its effective cytoprotective potential via a non-toxic induction of HO-1 in RAW264

Cajanus cajan Linn. (Leguminosae) prevents alcohol-induced rat liver damage and augments cytoprotective function.

PubMed

Kundu, Rakesh; Dasgupta, Suman; Biswas, Anindita; Bhattacharya, Anirban; Pal, Bikas C; Bandyopadhyay, Debashis; Bhattacharya, Shelley; Bhattacharya, Samir

2008-08-13

Cajanus cajan Linn. (Leguminosae) is a nontoxic edible herb, widely used in Indian folk medicine for the prevention of various liver disorders. In the present study we have demonstrated that methanol-aqueous fraction (MAF2) of Cajanus cajan leaf extract could prevent the chronically treated alcohol induced rat liver damage. Chronic doses of alcohol (3.7 g/ kg) orally administered to rats for 28 days and liver function marker enzymes such as GPT, GOT, ALP and anti-oxidant enzyme activities were determined. Effect of MAF2 at a dose of 50mg/kg body weight on alcohol treated rats was noted. Alcohol effected significant increase in liver marker enzyme activities and reduced the activities of anti-oxidant enzymes. Co-administration of MAF2 reversed the liver damage due to alcohol; it decreased the activities of liver marker enzymes and augmented antioxidant enzyme activities. We also demonstrate significant decrease of the phase II detoxifying enzyme, UDP-glucuronosyl transferase (UGT) activity along with a three- and two-fold decrease of UGT2B gene and protein expression respectively. MAF2 co-administration normalized UGT activity and revived the expression of UGT2B with a concomitant expression and nuclear translocation of Nrf2, a transcription factor that regulates the expression of many cytoprotective genes. Cajanus cajan extract therefore shows a promise in therapeutic use in alcohol induced liver dysfunction.

Hsp27 binding to the 3′UTR of bim mRNA prevents neuronal death during oxidative stress–induced injury: a novel cytoprotective mechanism

PubMed Central

Dávila, David; Jiménez-Mateos, Eva M.; Mooney, Claire M.; Velasco, Guillermo; Henshall, David C.; Prehn, Jochen H. M.

2014-01-01

Neurons face a changeable microenvironment and therefore need mechanisms that allow rapid switch on/off of their cytoprotective and apoptosis-inducing signaling pathways. Cellular mechanisms that control apoptosis activation include the regulation of pro/antiapoptotic mRNAs through their 3′-untranslated region (UTR). This region holds binding elements for RNA-binding proteins, which can control mRNA translation. Here we demonstrate that heat shock protein 27 (Hsp27) prevents oxidative stress–induced cell death in cerebellar granule neurons by specific regulation of the mRNA for the proapoptotic BH3-only protein, Bim. Hsp27 depletion induced by oxidative stress using hydrogen peroxide (H2O2) correlated with bim gene activation and subsequent neuronal death, whereas enhanced Hsp27 expression prevented these. This effect could not be explained by proteasomal degradation of Bim or bim promoter inhibition; however, it was associated with a specific increase in the levels of bim mRNA and with its binding to Hsp27. Finally, we determined that enhanced Hsp27 expression in neurons exposed to H2O2 or glutamate prevented the translation of a reporter plasmid where bim-3′UTR mRNA sequence was cloned downstream of a luciferase gene. These results suggest that repression of bim mRNA translation through binding to the 3′UTR constitutes a novel cytoprotective mechanism of Hsp27 during stress in neurons. PMID:25187648

Hepatic manifestations of non-steroidal inflammatory bowel disease therapy

PubMed Central

Hirten, Robert; Sultan, Keith; Thomas, Ashby; Bernstein, David E

2015-01-01

Inflammatory bowel disease (IBD) is composed of Crohn’s disease and ulcerative colitis and is manifested by both bowel-related and extraintestinal manifestations. Recently the number of therapeutic options available to treat IBD has dramatically increased, with each new medication having its own mechanism of action and side effect profile. A complete understanding of the hepatotoxicity of these medications is important in order to distinguish these complications from the hepatic manifestations of IBD. This review seeks to evaluate the hepatobiliary complications of non-steroid based IBD medications and aide providers in the recognition and management of these side-effects. PMID:26644815

Thymoquinone inhibits phorbol ester-induced activation of NF-κB and expression of COX-2, and induces expression of cytoprotective enzymes in mouse skin in vivo

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

Kundu, Joydeb Kumar; Liu, Lijia; Shin, Jun-Wan

2013-09-06

Highlights: •Thymoquinone inhibits phorbol ester-induced COX-2 expression in mouse skin. •Thymoquinone attenuates phosphorylation of IκBα and DNA binding of NF-κB in mouse skin. •Thymoquinone inhibits phosphorylation of p38 MAP kinase, JNK and Akt in mouse skin. •Thymoquinone induces the expression of cytoprotective proteins in mouse skin. -- Abstract: Thymoquinone (TQ), the active ingredient of Nigella sativa, has been reported to possess anti-inflammatory and chemopreventive properties. The present study was aimed at elucidating the molecular mechanisms of anti-inflammatory and antioxidative activities of thymoquinone in mouse skin. Pretreatment of female HR-1 hairless mouse skin with TQ attenuated 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of cyclooxygenase-2more » (COX-2). TQ diminished nuclear translocation and the DNA binding of nuclear factor-kappaB (NF-κB) via the blockade of phosphorylation and subsequent degradation of IκBα in TPA-treated mouse skin. Pretreatment with TQ attenuated the phosphorylation of Akt, c-Jun-N-terminal kinase and p38 mitogen-activated protein kinase, but not that of extracellular signal-regulated kinase-1/2. Moreover, topical application of TQ induced the expression of heme oxygenase-1, NAD(P)H-quinoneoxidoreductase-1, glutathione-S-transferase and glutamate cysteine ligase in mouse skin. Taken together, the inhibitory effects of TQ on TPA-induced COX-2 expression and NF-κB activation, and its ability to induce the expression of cytoprotective proteins provide a mechanistic basis of anti-inflammatory and antioxidative effects of TQ in hairless mouse skin.« less

Cytoprotective effect of lacritin on human corneal epithelial cells exposed to benzalkonium chloride in vitro

PubMed Central

Feng, Mary M.; Baryla, Julia; Liu, Hong; Laurie, Gordon W.; McKown, Robert L.; Ashki, Negin; Bhayana, Dinesh

2015-01-01

Purpose Benzalkonium chloride (BAK) is the most commonly found preservative in eye drops, and has been shown to cause ocular surface inflammation and toxicity. Lacritin is a human tear glycoprotein secreted from the lacrimal glands that has been found to be cytoprotective. This study was designed to determine if the presence of lacritin confers protection to a cultured human corneal epithelial (HCE) cell line, CRL-11515, and primary HCE cells after exposure to the ocular preservative agent BAK. Materials and Methods Recombinant human lacritin was cloned into intein fusion vectors, expressed in E. coli, and purified on chitin beads and DEAE Sepharose. Metabolic curves were established using the MTT assay after exposure of subconfluent CRL-11515 cells to BAK or lacritin. Western blot analysis of lipidated LC3 (LC3-II) provided a measure of autophagy in CRL-11515 cells exposed to lacritin and/or BAK. Results BAK reduced CRL-11515 cellular metabolic activity in a time and dose dependent manner. BAK-induced cellular stress was evident by elevated autophagy that increased with rising concentrations of BAK compared to control (P < 0.05). Lacritin increased HCE cell proliferation at an optimal dose of 1 nM. Preconditioning HCE cells with 1 nM lacritin for 24 hours prior to BAK exposure significantly dampened levels of LC3-II (P < 0.05) and promoted a significant increase in cellular metabolic activity (P < 0.01) compared to BAK alone. Conclusions These results suggest lacritin protects cultured HCE cells stressed with BAK. Lacritin may have the potential to be used as a topical adjunctive therapy in eyes chronically exposed to BAK. PMID:24401093

Cytoprotective effect of lacritin on human corneal epithelial cells exposed to benzalkonium chloride in vitro.

PubMed

Feng, Mary M; Baryla, Julia; Liu, Hong; Laurie, Gordon W; McKown, Robert L; Ashki, Negin; Bhayana, Dinesh; Hutnik, Cindy M L

2014-06-01

Benzalkonium chloride (BAK) is the most commonly found preservative in eye drops, and has been shown to cause ocular surface inflammation and toxicity. Lacritin is a human tear glycoprotein secreted from the lacrimal glands that has been found to be cytoprotective. This study was designed to determine if the presence of lacritin confers protection to a cultured human corneal epithelial (HCE) cell line, CRL-11515, and primary HCE cells after exposure to the ocular preservative agent BAK. Recombinant human lacritin was cloned into intein fusion vectors, expressed in E. coli, and purified on chitin beads and DEAE Sepharose. Metabolic curves were established using the MTT assay after exposure of sub-confluent CRL-11515 cells to BAK or lacritin. Western blot analysis of lipidated LC3 (LC3-II) provided a measure of autophagy in CRL-11515 cells exposed to lacritin and/or BAK. BAK reduced CRL-11515 cellular metabolic activity in a time- and dose-dependent manner. BAK-induced cellular stress was evident by elevated autophagy that increased with rising concentrations of BAK compared to control (p < 0.05). Lacritin increased HCE cell proliferation at an optimal dose of 1 nM. Preconditioning HCE cells with 1 nM lacritin for 24 h prior to BAK exposure significantly dampened levels of LC3-II (p < 0.05) and promoted a significant increase in cellular metabolic activity (p < 0.01) compared to BAK alone. These results suggest lacritin protects cultured HCE cells stressed with BAK. Lacritin may have the potential to be used as a topical adjunctive therapy in eyes chronically exposed to BAK.

A hybrid of coumarin and phenylsulfonylfuroxan induces caspase-dependent apoptosis and cytoprotective autophagy in lung adenocarcinoma cells.

PubMed

Wang, Qian; Guo, Yalan; Jiang, Shanshan; Dong, Mengxue; Kuerban, Kudelaidi; Li, Jiyang; Feng, Meiqing; Chen, Ying; Ye, Li

2018-01-15

Lung adenocarcinoma is the most primary histologic subtype of non-small cell lung cancer (NSCLC). Compound 8b, a novel coumarin derivative with phenylsulfonylfuroxan group, shows significant antiproliferation activity against lung adenocarcinoma cell with low toxicity. This study aims to uncover the potential of compound 8b in relation to apoptosis as well as autophagy induction in lung adenocarcinoma cells. The cytotoxicity and apoptosis of A549 and H1299 cells induced by compound 8b were detected by MTT, microscope and western blot analysis. Autophagy was determined by TEM, confocal microscopy and western blot analysis. Akt/mTOR and Erk signaling pathway were also examined by western blot analysis. First, significant growth inhibition and caspase-dependent apoptosis were observed in compound 8b-treated A549 and H1299 cells. Then, we confirmed compound 8b-induced autophagy by autophagosomes formation, upregulated expression of autophagy-related protein LC3-II and autophagic flux. Importantly, abolishing autophagy using inhibitors and ATG5 siRNA enhanced the cytotoxicity of compound 8b, indicating the cytoprotective role of autophagy in lung adenocarcinoma. Further mechanistic investigations suggested that Akt/mTOR and Erk signaling pathways contributed to autophagy induction by compound 8b. This results demonstrate that compound 8b induces caspase-dependent apoptosis as well as cytoprotective autophagy in lung adenocarcinoma cells, which may provide scientific evidence for developing this furoxan-based NO-releasing coumarin derivative as a potential anti-lung adenocarcinoma therapeutic agents. Copyright © 2017 Elsevier GmbH. All rights reserved.

Neurologic manifestations of hypothyroidism in dogs.

PubMed

Bertalan, Abigail; Kent, Marc; Glass, Eric

2013-03-01

Hypothyroidism is a common endocrine disease in dogs. A variety of clinicopathologic abnormalities may be present; however, neurologic deficits are rare. In some instances, neurologic deficits may be the sole manifestation of hypothyroidism. Consequent ly, the diagnosis and management of the neurologic disorders associated with hypothyroidism can be challenging. This article describes several neurologic manifestations of primary hypothyroidism in dogs; discusses the pathophysiology of hypothyroidism-induced neurologic disorders affecting the peripheral and central nervous systems; and reviews the evidence for the neurologic effects of hypothyroidism.

Ca2+-Dependent Cytoprotective Effects of Ursodeoxycholic and Tauroursodeoxycholic Acid on the Biliary Epithelium in a Rat Model of Cholestasis and Loss of Bile Ducts

PubMed Central

Marzioni, Marco; Francis, Heather; Benedetti, Antonio; Ueno, Yoshiyuki; Fava, Giammarco; Venter, Juliet; Reichenbach, Ramona; Mancino, Maria Grazia; Summers, Ryun; Alpini, Gianfranco; Glaser, Shannon

2006-01-01

Chronic cholestatic liver diseases are characterized by impaired balance between proliferation and death of cholangiocytes, as well as vanishing of bile ducts and liver failure. Ursodeoxycholic acid (UDCA) is a bile acid widely used for the therapy of cholangiopathies. However, little is known of the cytoprotective effects of UDCA on cholangiocytes. Therefore, UDCA and its taurine conjugate tauroursodeoxycholic acid (TUDCA) were administered in vivo to rats simultaneously subjected to bile duct ligation and vagotomy, a model that induces cholestasis and loss of bile ducts by apoptosis of cholangiocytes. Because these two bile acids act through Ca2+ signaling, animals were also treated with BAPTA/AM (an intracellular Ca2+ chelator) or Gö6976 (a Ca2+-dependent protein kinase C-α inhibitor). The administration of UDCA or TUDCA prevented the induction of apoptosis and the loss of proliferative and functional responses observed in the bile duct ligation-vagotomized rats. These effects were neutralized by the simultaneous administration of BAPTA/AM or Gö6976. UDCA and TUDCA enhanced intracellular Ca2+ and IP3 levels, together with increased phosphorylation of protein kinase C-α. Parallel changes were observed regarding the activation of the MAPK and PI3K pathways, changes that were abolished by addition of BAPTA/AM or Gö6976. These studies provide information that may improve the response of cholangiopathies to medical therapy. PMID:16436655

Cyclo(His-Pro) promotes cytoprotection by activating Nrf2-mediated up-regulation of antioxidant defence

PubMed Central

Minelli, Alba; Conte, Carmela; Grottelli, Silvia; Bellezza, Maria; Cacciatore, Ivana; Bolaños, Juan P

2009-01-01

Hystidyl-proline [cyclo(His-Pro)] is an endogenous cyclic dipeptide produced by the cleavage of thyrotropin releasing hormone. Previous studies have shown that cyclo(His-Pro) protects against oxidative stress, although the underlying mechanism has remained elusive. Here, we addressed this issue and found that cyclo(His-Pro) triggered nuclear accumulation of NF-E2-related factor-2 (Nrf2), a transcription factor that up-regulates antioxidant-/electrophile-responsive element (ARE-EpRE)-related genes, in PC12 cells. Cyclo(His-Pro) attenuated reactive oxygen species production, and prevented glutathione depletion caused by glutamate, rotenone, paraquat and β-amyloid treatment. Moreover, real-time PCR analyses revealed that cyclo(His-Pro) induced the expression of a number of ARE-related genes and protected cells against hydrogen peroxide-mediated apoptotic death. Furthermore, these effects were abolished by RNA interference-mediated Nrf2 knockdown. Finally, pharmacological inhibition of p-38 MAPK partially prevented both cyclo(His-Pro)-mediated Nrf2 activation and cellular protection. These results suggest that the signalling mechanism responsible for the cytoprotective actions of cyclo(His-Pro) would involve p-38 MAPK activation leading to Nrf2-mediated up-regulation of antioxidant cellular defence. PMID:18373731

[Cytoprotection with amifostine in radiotherapy or radio-chemotherapy of head and neck tumors].

PubMed

Altmann, S; Hoffmanns, H

1999-11-01

A considerable amount of experimental and clinical data prove the cytoprotective effect of amifostine on normal tissue exposed to different types of antineoplastic treatments. The present study examines its influence on the short-term toxicity of either radiotherapy alone or combined radio-chemotherapy in patients with advanced head and neck cancer. Twenty-three patients with advanced head and neck cancer, mainly Stage III and IV, were treated with preoperative radiation (n = 1), pre- as well as postoperative radiotherapy (n = 5), postoperative radiation (n = 9) or combined postoperative radio-chemotherapy (n = 6). Before each radiation application a total dose of 500 mg amifostine was administered intravenously over 15 minutes. The documentation of this unselected patient group was compared retrospectively to a historical control group comprising 17 patients. In 15 patients (65%) of the amifostine group, therapy induced side effects such as mucositis and dermatitis of WHO Grade < or = 2 were detected, requiring interruptions of the radiotherapy (mean: 6.5, maximum 17 days). No mucosa or dermatologic toxicity of WHO Grade 3 or 4 was observed in this group. Significantly more acute toxicity was detected in the historical control group. Stomatitis or epitheliolysis of WHO Grade 3 occurred in 7 patients (41%). The side effects induced by the antineoplastic therapy caused an interruption of treatment in 15 patients (88%) (mean: 16, maximum 40 days; p = 0.0016). The application of amifostine before each radiation treatment seems to result in a distinct reduction of short-term toxicity of radiotherapy or combined radio-chemotherapy in patients with head and neck cancer, allowing for a better adherence to the planned radiation time schedule.

Ophthalmologic manifestations of celiac disease

PubMed Central

Martins, Thiago Gonçalves dos Santos; Costa, Ana Luiza Fontes de Azevedo; Oyamada, Maria Kiyoko; Schor, Paulo; Sipahi, Aytan Miranda

2016-01-01

Celiac disease is an autoimmune disorder that affects the small intestine of genetically predisposed individuals. Ophthalmic manifestations are within the extra-intestinal manifestations, and can be divided into those of autoimmune disorders or those due to absorptive disabilities. This article reviewed the ophthalmologic manifestation of celiac disease. Ophthalmic symptoms are rare, but should be investigated in patients with celiac disease and taken into consideration as the first systemic manifestation. PMID:26949627

Sclerodermatomyositis, ocular manifestations.

PubMed

Pedroza-Seres, M; Serna-Ojeda, J C; Flores-Suárez, L F

2017-07-01

Sclerodermatomyositis is an overlap syndrome of myositis and scleroderma, with dermatological, muscular and joint involvement, but may also present with ocular manifestations. A 57 year-old woman presented with ophthalmological manifestations, including scleral thinning 360°, and the presence of cells in the anterior and posterior chamber. Oriented physical examination and laboratory studies led to the diagnosis, with the need for systemic treatment. Sclerodermatomyositis is a rare disease. Its diagnosis needs thorough clinical and laboratory studies, and its management should be multidisciplinary when inflammatory ocular manifestations may be present. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Selective Akt Inhibitors Synergize with Tyrosine Kinase Inhibitors and Effectively Override Stroma-Associated Cytoprotection of Mutant FLT3-Positive AML Cells

PubMed Central

Zhang, Xin; Nelson, Erik; Sattler, Martin; Liu, Feiyang; Nicolais, Maria; Zhang, Jianming; Mitsiades, Constantine; Smith, Robert W.; Stone, Richard; Galinsky, Ilene; Nonami, Atsushi; Griffin, James D.; Gray, Nathanael

2013-01-01

Objectives Tyrosine kinase inhibitor (TKI)-treated acute myeloid leukemia (AML) patients commonly show rapid and significant peripheral blood blast cell reduction, however a marginal decrease in bone marrow blasts. This suggests a protective environment and highlights the demand for a better understanding of stromal:leukemia cell communication. As a strategy to improve clinical efficacy, we searched for novel agents capable of potentiating the stroma-diminished effects of TKI treatment of mutant FLT3-expressing cells. Methods We designed a combinatorial high throughput drug screen using well-characterized kinase inhibitor-focused libraries to identify novel kinase inhibitors capable of overriding stromal-mediated resistance to TKIs, such as PKC412 and AC220. Standard liquid culture proliferation assays, cell cycle and apoptosis analysis, and immunoblotting were carried out with cell lines or primary AML to validate putative candidates from the screen and characterize the mechanism(s) underlying observed synergy. Results and Conclusions Our study led to the observation of synergy between selective Akt inhibitors and FLT3 inhibitors against mutant FLT3-positive AML in either the absence or presence of stroma. Our findings are consistent with evidence that Akt activation is characteristic of mutant FLT3-transformed cells, as well as observed residual Akt activity following FLT3 inhibitor treatment. In conclusion, our study highlights the potential importance of Akt as a signaling factor in leukemia survival, and supports the use of the co-culture chemical screen to identify agents able to potentiate TKI anti-leukemia activity in a cytoprotective microenvironment. PMID:23437141

Cardiovascular manifestations of phaeochromocytoma.

PubMed

Prejbisz, Aleksander; Lenders, Jacques W M; Eisenhofer, Graeme; Januszewicz, Andrzej

2011-11-01

Clinical expression of phaeochromocytoma may involve numerous cardiovascular manifestations, but usually presents as sustained or paroxysmal hypertension associated with other signs and symptoms of catecholamine excess. Most of the life-threatening cardiovascular manifestations of phaeochromocytoma, such as hypertensive emergencies, result from a rapid and massive release of catecholamines from the tumour. More rarely, patients with phaeochromocytoma present with low blood pressure or even shock that may then precede multisystem crisis. Sinus tachycardia, with palpitations as the presenting symptom, is the most prevalent abnormality of cardiac rhythm in phaeochromocytoma, but tumours can also be associated with more serious ventricular arrhythmias or conduction disturbances. Reversible dilated or hypertrophic cardiomyopathy are well established cardiac manifestations of phaeochromocytoma, with more recent attention to an increasing number of cases with Takotsubo cardiomyopathy. This review provides an update on the cause, clinical presentation and treatment of the cardiovascular manifestations of phaeochromocytoma. As the cardiovascular complications of phaeochromocytoma can be life-threatening, all patients who present with manifestations that even remotely suggest excessive catecholamine secretion should be screened for the disease.

Cutaneous Manifestation of Food Allergy.

PubMed

Tam, Jonathan S

2017-02-01

Hypersensitivity reactions to foods can have diverse and highly variable manifestations. Cutaneous reactions, such as acute urticaria and angioedema, are among the most common manifestations of food allergy. However, cutaneous manifestations of food allergy encompass more than just IgE-mediated processes and include atopic dermatitis, contact dermatitis, and even dermatitis herpetiformis. These cutaneous manifestations provide an opportunity to better understand the diversity of adverse immunologic responses to food and the interconnected pathways that produce them. Copyright © 2016 Elsevier Inc. All rights reserved.

Neuropsychiatric Manifestations of Scrub Typhus.

PubMed

Mahajan, Sanjay K; Mahajan, Sanyam K

2017-01-01

Scrub typhus is caused by Orientia tsutsugamushi characterized by focal or disseminated vasculitis and perivasculitis which may involve the lungs, heart, liver, spleen and central nervous system. It was thought to have been eradicated from India. Recently it is being reported from many areas of India. The clinical picture and severity of the symptoms varies widely. The neurological manifestations of scrub typhus are not uncommon but are diverse. Meningoencephalitis is classical manifestation of scrub typhus but cerebellitis, cranial nerve palsies, plexopathy, transverse myelitis, neuroleptic malignant syndrome and Guillan-Barré syndrome are other manifestations reported in literature. The availability of literature on the neurological manifestations of scrub typhus is limited to case reports mainly. This article reviews various neurological manifestations of scrub typhus reported in literature.

Disrupted chronobiology of sleep and cytoprotection in obesity: possible therapeutic value of melatonin.

PubMed

Cardinali, Daniel P; Pagano, Eleonora S; Scacchi Bernasconi, Pablo A; Reynoso, Roxana; Scacchi, Pablo

2011-01-01

From a physiological perspective the sleep-wake cycle can be envisioned as a sequence of three physiological states (wakefulness, non-rapid eye movement, NREM, sleep and REM sleep) which are defined by a particular neuroendocrine-immune profile regulating the metabolic balance, body weight and inflammatory responses. Sleep deprivation and circadian disruption in contemporary "24/7 Society" lead to the predominance of pro-orexic and proinflammatory mechanisms that contribute to a pandemic metabolic syndrome (MS) including obesity, diabetes and atherosclerotic disease. Thus, a successful management of MS may require a drug that besides antagonizing the trigger factors of MS could also correct a disturbed sleep-wake rhythm. This review deals with the analysis of the therapeutic validity of melatonin in MS. Melatonin is an effective chronobiotic agent changing the phase and amplitude of the sleep/wake rhythm and having cytoprotective and immunomodulatory properties useful to prevent a number of MS sequels. Several studies support that melatonin can prevent hyperadiposity in animal models of obesity. Melatonin at a low dose (2-5 mg/day) has been used for improving sleep in patients with insomnia and circadian rhythm sleep disorders. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects (ramelteon, agomelatine, tasimelteon, TK 301). In clinical trials these analogs were employed in doses considerably higher than those usually employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin doses in the range of 50-100 mg/day are needed to assess its therapeutic value in MS.

Haematological manifestations of lupus

PubMed Central

Fayyaz, Anum; Igoe, Ann; Kurien, Biji T; Danda, Debashish; James, Judith A; Stafford, Haraldine A; Scofield, R Hal

2015-01-01

Our purpose was to compile information on the haematological manifestations of systemic lupus erythematosus (SLE), namely leucopenia, lymphopenia, thrombocytopenia, autoimmune haemolytic anaemia (AIHA), thrombotic thrombocytopenic purpura (TTP) and myelofibrosis. During our search of the English-language MEDLINE sources, we did not place a date-of-publication constraint. Hence, we have reviewed previous as well as most recent studies with the subject heading SLE in combination with each manifestation. Neutropenia can lead to morbidity and mortality from increased susceptibility to infection. Severe neutropenia can be successfully treated with granulocyte colony-stimulating factor. While related to disease activity, there is no specific therapy for lymphopenia. Severe lymphopenia may require the use of prophylactic therapy to prevent select opportunistic infections. Isolated idiopathic thrombocytopenic purpura maybe the first manifestation of SLE by months or even years. Some manifestations of lupus occur more frequently in association with low platelet count in these patients, for example, neuropsychiatric manifestation, haemolytic anaemia, the antiphospholipid syndrome and renal disease. Thrombocytopenia can be regarded as an important prognostic indicator of survival in patients with SLE. Medical, surgical and biological treatment modalities are reviewed for this manifestation. First-line therapy remains glucocorticoids. Through our review, we conclude glucocorticoids do produce a response in majority of patients initially, but sustained response to therapy is unlikely. Glucocorticoids are used as first-line therapy in patients with SLE with AIHA, but there is no conclusive evidence to guide second-line therapy. Rituximab is promising in refractory and non-responding AIHA. TTP is not recognised as a criteria for classification of SLE, but there is a considerable overlap between the presenting features of TTP and SLE, and a few patients with SLE have concurrent

HIV-1 Gp120 clade B/C induces a GRP78 driven cytoprotective mechanism in astrocytoma

PubMed Central

López, Sheila N.; Rodríguez-Valentín, Madeline; Rivera, Mariela; Rodríguez, Maridaliz; Babu, Mohan; Cubano, Luis A.; Xiong, Huangui; Wang, Guangdi; Kucheryavykh, Lilia; Boukli, Nawal M.

2017-01-01

HIV-1 clades are known to be one of the key factors implicated in modulating HIV-associated neurocognitive disorders. HIV-1 B and C clades account for the majority of HIV-1 infections, clade B being the most neuropathogenic. The mechanisms behind HIV-mediated neuropathogenesis remain the subject of active research. We hypothesized that HIV-1 gp120 clade B and C proteins may exert differential proliferation, cell survival and NeuroAIDS effects in human astrocytoma cells via the Unfolded Protein Response, an endoplasmic reticulum- based cytoprotective mechanism. The differential effect of gp120 clade B and C was evaluated using for the first time a Tandem Mass Tag isobaric labeling quantitative proteomic approach. Flow cytometry analyses were performed for cell cycle and cell death identification. Among the proteins differentiated by HIV-1 gp120 proteins figure cytoskeleton, oxidative stress, UPR markers and numerous glycolytic metabolism enzymes. Our results demonstrate that HIV-1 gp120 B induced migration, proliferative and protective responses granted by the expression of GRP78, while HIV-1 gp120 C induced the expression of key inflammatory and pro-apoptotic markers. These novel findings put forward the first evidence that GRP78 is a key player in HIV-1 clade B and C neuropathogenic discrepancies and can be used as a novel target for immunotherapies. PMID:28978127

In vitro antioxidant and cytoprotective properties of Maillard reaction products from phloridzin-amino acid model systems.

PubMed

Han, Linna; Li, Feng; Yu, Qijian; Li, Dapeng

2018-01-01

The aim of this study was to investigate in vitro antioxidant activities and cytoprotective effect of Maillard reaction products (MRPs) from phloridzin (Pz)-amino acid model systems. Their structures were also characterised by Fourier transform-infrared spectroscopy (FTIR). MRPs were prepared from the Pz-methionine (Met), Pz-lysine (Lys), Pz-isoleucine (Ile), Pz-histidine (His) or Pz-glutamic acid (Glu) model system. The Pz-Lys MRPs, rich in antioxidant potency, were subjected to ultrafiltration to yield four MRPs fractions with different molecular weights (Mw). The fraction with Mw 30-50 kDa had significantly (P < 0.05) higher antioxidant activity than other fractions. Moreover, it significantly (P < 0.05) attenuated the 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH)-elicited decrease in cell viability in HepG2 cells in a concentration-dependent manner. FTIR analysis indicated that the fraction with Mw 30-50 kDa had the strong stretching vibration for the OH, NH, CH, CO and CC groups, suggesting the formation of intermediate MRPs during Maillard reaction. The results obtained in this study may provide some basis for the purported health-promoting effects of MRPs and their potential application as antioxidant agents in food industry. Also, it is important for our understanding of the variation of bioactive substances in food during thermal processing. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Experimental basis for a role for sulfhydryls and dopamine in ulcerogenesis: a primer for cytoprotection--organoprotection.

PubMed

Szabo, S

1986-01-01

This brief review presents the evolution of the concept of cytoprotection which was originally described by Robert (1979) to represent prevention of chemically induced hemorrhagic gastric erosions without inhibiting acid secretion. Prostaglandins (PG) and sulfhydryls (SH) protect only against deep hemorrhagic necrosis in the mucosa without altering the initial damage to surface epithelial cells. Organ integrity and function are thus maintained (i.e., organoprotection) despite the loss of several layers of mucosal cells. While both PG and SH are natural products it must be stressed that only SH compounds can enter directly into protective reactions (e.g., free radical scavenging, modification of receptor SH groups, oxidation of certain structural and enzyme proteins). In addition, SH compounds also stimulate PG synthesis. A major target of gastroprotection by either PG or SH is the preservation of mucosal microvasculature to maintain blood flow for rapid restitution and cell proliferation. Dopamine-related compounds are reviewed because of their possible role in duodenal ulceration. Dopamine and dopamine agonists are antiulcerogens in duodenal ulcer models. Dopamine antagonists are proulcerogens and the dopamine neurotoxin MPTP causes duodenal ulcer in experimental animals. The mechanism of duodenal antiulcerogenic effect involves inhibition of gastric acid and pepsin secretion, stimulation of duodenal bicarbonate secretion, correction of duodenal dysmotility, and maybe increased blood flow. Because of their multiple beneficial effects, SH compounds and dopamine drugs are good models for gastroenteroprotection.

Neuropsychiatric Manifestations of Scrub Typhus

PubMed Central

Mahajan, Sanjay K.; Mahajan, Sanyam K.

2017-01-01

Scrub typhus is caused by Orientia tsutsugamushi characterized by focal or disseminated vasculitis and perivasculitis which may involve the lungs, heart, liver, spleen and central nervous system. It was thought to have been eradicated from India. Recently it is being reported from many areas of India. The clinical picture and severity of the symptoms varies widely. The neurological manifestations of scrub typhus are not uncommon but are diverse. Meningoencephalitis is classical manifestation of scrub typhus but cerebellitis, cranial nerve palsies, plexopathy, transverse myelitis, neuroleptic malignant syndrome and Guillan-Barré syndrome are other manifestations reported in literature. The availability of literature on the neurological manifestations of scrub typhus is limited to case reports mainly. This article reviews various neurological manifestations of scrub typhus reported in literature. PMID:28694624

Ocular Manifestations of Acquired Immunodeficiency Syndrome.

PubMed

Kim, Young Shin; Sun, Hae Jung; Kim, Tae Hyong; Kang, Kui Dong; Lee, Sung Jin

2015-08-01

To investigate the patterns and risk factors of the ocular manifestations of acquired immunodeficiency syndrome (AIDS) and their correlation with CD4+ count in the era of highly active antiretroviral therapy (HAART). This retrospective study examined 127 AIDS patients who presented to Soonchunhyang University Hospital. Data were collected from patient interviews, clinical examinations, and laboratory investigations. Ophthalmologic examinations included the best-corrected visual acuity, intraocular pressure, anterior segment and adnexal examination, and dilated fundus examination. Of the 127 patients with AIDS, 118 were on HAART and 9 were not. The mean CD4+ count was 266.7 ± 209.1 cells/µL. There were ocular manifestations in 61 patients (48.0%). The incidence of anterior segment manifestations was higher than posterior segment manifestations at 28.3% and 19.7%, respectively. The mean CD4+ count was significantly (p < 0.05) lower in the patients with posterior versus anterior segment ocular manifestations. The most common ocular manifestation was retinal microvasculopathy (15.0%), followed by keratoconjunctivitis sicca (14.2%), conjunctival microvasculopathy (9.4%), cytomegalovirus retinitis (3.1%), herpes zoster ophthalmicus (2.4%), and blepharitis (1.6%). Retinal microvasculopathy and cytomegalovirus retinitis were common in patients with CD4+ counts <200 cells/µL, while keratoconjunctivitis sicca and conjunctival microvasculopathy were common in patients with CD4+ counts of 200 to 499 cells/µL. There was a significant (p < 0.05) association between ocular manifestation and CD4+ count or age. The introduction of HAART has changed the landscape of ocular presentations in patients with AIDS. In this study, anterior segment and external ocular manifestations occurred more frequently than posterior segment manifestations. Also, the mean CD4+ count was significantly lower in patients with posterior segment ocular manifestations versus anterior segment ocular

Hsp27 binding to the 3'UTR of bim mRNA prevents neuronal death during oxidative stress-induced injury: a novel cytoprotective mechanism.

PubMed

Dávila, David; Jiménez-Mateos, Eva M; Mooney, Claire M; Velasco, Guillermo; Henshall, David C; Prehn, Jochen H M

2014-11-01

Neurons face a changeable microenvironment and therefore need mechanisms that allow rapid switch on/off of their cytoprotective and apoptosis-inducing signaling pathways. Cellular mechanisms that control apoptosis activation include the regulation of pro/antiapoptotic mRNAs through their 3'-untranslated region (UTR). This region holds binding elements for RNA-binding proteins, which can control mRNA translation. Here we demonstrate that heat shock protein 27 (Hsp27) prevents oxidative stress-induced cell death in cerebellar granule neurons by specific regulation of the mRNA for the proapoptotic BH3-only protein, Bim. Hsp27 depletion induced by oxidative stress using hydrogen peroxide (H2O2) correlated with bim gene activation and subsequent neuronal death, whereas enhanced Hsp27 expression prevented these. This effect could not be explained by proteasomal degradation of Bim or bim promoter inhibition; however, it was associated with a specific increase in the levels of bim mRNA and with its binding to Hsp27. Finally, we determined that enhanced Hsp27 expression in neurons exposed to H2O2 or glutamate prevented the translation of a reporter plasmid where bim-3'UTR mRNA sequence was cloned downstream of a luciferase gene. These results suggest that repression of bim mRNA translation through binding to the 3'UTR constitutes a novel cytoprotective mechanism of Hsp27 during stress in neurons. © 2014 Dávila et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

The MANIFEST prototyping design study

NASA Astrophysics Data System (ADS)

Lawrence, Jonathan S.; Ben-Ami, Sagi; Brown, David M.; Brown, Rebecca A.; Case, Scott; Chapman, Steve; Churilov, Vladimir; Colless, Matthew; Content, Robert; Depoy, Darren; Evans, Ian; Farrell, Tony; Goodwin, Michael; Jacoby, George; Klauser, Urs; Kuehn, Kyler; Lorente, Nuria P. F.; Mali, Slavko; Marshall, Jennifer; Muller, Rolf; Nichani, Vijay; Pai, Naveen; Prochaska, Travis; Saunders, Will; Schmidt, Luke; Shortridge, Keith; Staszak, Nicholas F.; Szentgyorgyi, Andrew; Tims, Julia; Vuong, Minh V.; Waller, Lewis G.; Zhelem, Ross

2016-08-01

MANIFEST is a facility multi-object fibre system for the Giant Magellan Telescope, which uses `Starbug' fibre positioning robots. MANIFEST, when coupled to the telescope's planned seeing-limited instruments, GMACS, and G-CLEF, offers access to: larger fields of view; higher multiplex gains; versatile reformatting of the focal plane via IFUs; image-slicers; and in some cases higher spatial and spectral resolution. The Prototyping Design Study phase for MANIFEST, nearing completion, has focused on developing a working prototype of a Starbugs system, called TAIPAN, for the UK Schmidt Telescope, which will conduct a stellar and galaxy survey of the Southern sky. The Prototyping Design Study has also included work on the GMT instrument interfaces. In this paper, we outline the instrument design features of TAIPAN, highlight the modifications that will be necessary for the MANIFEST implementation, and provide an update on the MANIFEST/instrument interfaces.

Ocular Manifestations of Acquired Immunodeficiency Syndrome

PubMed Central

Kim, Young Shin; Sun, Hae Jung; Kim, Tae Hyong; Kang, Kui Dong

2015-01-01

Purpose To investigate the patterns and risk factors of the ocular manifestations of acquired immunodeficiency syndrome (AIDS) and their correlation with CD4+ count in the era of highly active antiretroviral therapy (HAART). Methods This retrospective study examined 127 AIDS patients who presented to Soonchunhyang University Hospital. Data were collected from patient interviews, clinical examinations, and laboratory investigations. Ophthalmologic examinations included the best-corrected visual acuity, intraocular pressure, anterior segment and adnexal examination, and dilated fundus examination. Results Of the 127 patients with AIDS, 118 were on HAART and 9 were not. The mean CD4+ count was 266.7 ± 209.1 cells/µL. There were ocular manifestations in 61 patients (48.0%). The incidence of anterior segment manifestations was higher than posterior segment manifestations at 28.3% and 19.7%, respectively. The mean CD4+ count was significantly (p < 0.05) lower in the patients with posterior versus anterior segment ocular manifestations. The most common ocular manifestation was retinal microvasculopathy (15.0%), followed by keratoconjunctivitis sicca (14.2%), conjunctival microvasculopathy (9.4%), cytomegalovirus retinitis (3.1%), herpes zoster ophthalmicus (2.4%), and blepharitis (1.6%). Retinal microvasculopathy and cytomegalovirus retinitis were common in patients with CD4+ counts <200 cells/µL, while keratoconjunctivitis sicca and conjunctival microvasculopathy were common in patients with CD4+ counts of 200 to 499 cells/µL. There was a significant (p < 0.05) association between ocular manifestation and CD4+ count or age. Conclusions The introduction of HAART has changed the landscape of ocular presentations in patients with AIDS. In this study, anterior segment and external ocular manifestations occurred more frequently than posterior segment manifestations. Also, the mean CD4+ count was significantly lower in patients with posterior segment ocular manifestations

Musculoskeletal manifestations in diabetic versus prediabetic patients.

PubMed

Fatemi, Alimohammad; Iraj, Bijan; Barzanian, Jafar; Maracy, Mohammadreza; Smiley, Abbas

2015-09-01

This study was carried out to evaluate the prevalence of musculoskeletal manifestations in a sample of patients with diabetes mellitus (DM) and those with prediabetes and compare the findings between the two groups. One hundred and eighty-eight patients with DM and 125 prediabetic subjects were randomly enrolled in this cross-sectional study. Demographic data and past history were recorded. Musculoskeletal physical examinations were done by a single rheumatologist. Regression analyses were employed to assess the crude and adjusted effects of determinants on DM musculoskeletal manifestations (DMMMs). Female/male ratio was not significantly different between diabetic and prediabetic patients (4.4 vs. 4.7, respectively, P = 0.9). However, diabetic patients were significantly older than the prediabetic ones (56.6 vs. 52 years, respectively, P = 0.0001); 83.5% of diabetic patients and 52.8% of prediabetic ones had at least one musculoskeletal manifestation (P = 0.0001). The prevalence of knee osteoarthritis and shoulder involvement were almost two times more common (P = 0.0001 and P = 0.015) in diabetic patients than in prediabetic ones (73.4% vs. 38% and 21.2% vs. 9.5%, respectively). Prevalence of carpal tunnel syndrome (CTS) was 48% and 36.5% in patients with diabetes and prediabetes, respectively (P = 0.053). Multivariate backward regression analysis showed age, sex, BMI (body mass index) and DM as the significant determinants in development of musculoskeletal manifestations in all subjects. Age and BMI were the only significant factors associated with musculoskeletal manifestations in both diabetic and prediabetic patients. Diabetic and prediabetic patients may show high prevalence of musculoskeletal manifestations. In non-diabetic patients diagnosed with CTS, prediabetes might be ruled out. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Effects of heat shock, stannous chloride, and gallium nitrate on the rat inflammatory response.

PubMed

House, S D; Guidon, P T; Perdrizet, G A; Rewinski, M; Kyriakos, R; Bockman, R S; Mistry, T; Gallagher, R A; Hightower, L E

2001-04-01

Heat and a variety of other stressors cause mammalian cells and tissues to acquire cytoprotection. This transient state of altered cellular physiology is nonproliferative and antiapoptotic. In this study, male Wistar rats were stress conditioned with either stannous chloride or gallium nitrate, which have immunosuppressive effects in vivo and in vitro, or heat shock, the most intensively studied inducer of cytoprotection. The early stages of inflammation in response to topical suffusion of mesentery tissue with formyl-methionyl-leucyl-phenylalanine (FMLP) were monitored using intravital microscopy. Microvascular hemodynamics (venular diameter, red blood cell velocity [Vrbc], white blood cell [WBC] flux, and leukocyte-endothelial adhesion [LEA]) were used as indicators of inflammation, and tissue levels of inducible Hsp70, determined using immunoblot assays, provided a marker of cytoprotection. None of the experimental treatments blocked decreases in WBC flux during FMLP suffusion, an indicator of increased low-affinity interactions between leukocytes and vascular endothelium known as rolling adhesion. During FMLP suffusion LEA, an indicator of firm attachment between leukocytes and vascular endothelial cells increased in placebo and gallium nitrate-treated animals but not in heat- and stannous chloride-treated animals, an anti-inflammatory effect. Hsp70 was not detected in aortic tissue from placebo and gallium nitrate-treated animals, indicating that Hsp70-dependent cytoprotection was not present. In contrast, Hsp70 was detected in aortic tissues from heat- and stannous chloride-treated animals, indicating that these tissues were in a cytoprotected state that was also an anti-inflammatory state.

Nasal manifestations in chromium industry workers.

PubMed

Aiyer, R G; Kumar, Gaurav

2003-04-01

People working in mines, plating factories, cement industries are mainly exposed to chrome substances, IIexavalent chromium has been implicated for its toxic effect on the nasal mucosa. Hereby we present a rare study of 28 patients who attended out patient department of Otorhinolaryngology at SSG Hospital, Baroda from a nearby chromium industry. This study aims to present various nasal manifestations of toxic effects of prolonged chromium exposure.

I1 Imidazoline Receptor: Novel Potential Cytoprotective Target of TVP1022, the S-Enantiomer of Rasagiline

PubMed Central

Frolov, Luba; Ovcharenko, Elena; Angel, Itzchak; Youdim, Moussa B. H.; Binah, Ofer

2012-01-01

TVP1022, the S-enantiomer of rasagiline (Azilect®) (N-propargyl-1R-aminoindan), exerts cyto/cardio-protective effects in a variety of experimental cardiac and neuronal models. Previous studies have demonstrated that the protective activity of TVP1022 and other propargyl derivatives involve the activation of p42/44 mitogen-activated protein kinase (MAPK) signaling pathway. In the current study, we further investigated the molecular mechanism of action and signaling pathways of TVP1022 which may account for the cyto/cardio-protective efficacy of the drug. Using specific receptor binding and enzyme assays, we demonstrated that the imidazoline 1 and 2 binding sites (I1 & I2) are potential targets for TVP1022 (IC50 = 9.5E-08 M and IC50 = 1.4E-07 M, respectively). Western blotting analysis showed that TVP1022 (1–20 µM) dose-dependently increased the immunoreactivity of phosphorylated p42 and p44 MAPK in rat pheochromocytoma PC12 cells and in neonatal rat ventricular myocytes (NRVM). This effect of TVP1022 was significantly attenuated by efaroxan, a selective I1 imidazoline receptor antagonist. In addition, the cytoprotective effect of TVP1022 demonstrated in NRVM against serum deprivation-induced toxicity was markedly inhibited by efaroxan, thus suggesting the importance of I1imidazoline receptor in mediating the cardioprotective activity of the drug. Our findings suggest that the I1imidazoline receptor represents a novel site of action for the cyto/cardio-protective efficacy of TVP1022. PMID:23166584

I1 imidazoline receptor: novel potential cytoprotective target of TVP1022, the S-enantiomer of rasagiline.

PubMed

Barac, Yaron D; Bar-Am, Orit; Liani, Esti; Amit, Tamar; Frolov, Luba; Ovcharenko, Elena; Angel, Itzchak; Youdim, Moussa B H; Binah, Ofer

2012-01-01

TVP1022, the S-enantiomer of rasagiline (Azilect®) (N-propargyl-1R-aminoindan), exerts cyto/cardio-protective effects in a variety of experimental cardiac and neuronal models. Previous studies have demonstrated that the protective activity of TVP1022 and other propargyl derivatives involve the activation of p42/44 mitogen-activated protein kinase (MAPK) signaling pathway. In the current study, we further investigated the molecular mechanism of action and signaling pathways of TVP1022 which may account for the cyto/cardio-protective efficacy of the drug. Using specific receptor binding and enzyme assays, we demonstrated that the imidazoline 1 and 2 binding sites (I(1) & I(2)) are potential targets for TVP1022 (IC(50) =9.5E-08 M and IC(50) =1.4E-07 M, respectively). Western blotting analysis showed that TVP1022 (1-20 µM) dose-dependently increased the immunoreactivity of phosphorylated p42 and p44 MAPK in rat pheochromocytoma PC12 cells and in neonatal rat ventricular myocytes (NRVM). This effect of TVP1022 was significantly attenuated by efaroxan, a selective I(1) imidazoline receptor antagonist. In addition, the cytoprotective effect of TVP1022 demonstrated in NRVM against serum deprivation-induced toxicity was markedly inhibited by efaroxan, thus suggesting the importance of I(1)imidazoline receptor in mediating the cardioprotective activity of the drug. Our findings suggest that the I(1)imidazoline receptor represents a novel site of action for the cyto/cardio-protective efficacy of TVP1022.

40 CFR 761.215 - Manifest discrepancies.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROHIBITIONS PCB Waste Disposal Records and Reports § 761.215 Manifest discrepancies. (a) Manifest... Section 761.215 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES... quantity or type of PCB waste designated on the manifest or shipping paper, and the quantity and type of...

40 CFR 761.215 - Manifest discrepancies.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PROHIBITIONS PCB Waste Disposal Records and Reports § 761.215 Manifest discrepancies. (a) Manifest... Section 761.215 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES... quantity or type of PCB waste designated on the manifest or shipping paper, and the quantity and type of...

Determination of the anti-inflammatory and cytoprotective effects of l-glutamine and l-alanine, or dipeptide, supplementation in rats submitted to resistance exercise.

PubMed

Raizel, Raquel; Leite, Jaqueline Santos Moreira; Hypólito, Thaís Menezes; Coqueiro, Audrey Yule; Newsholme, Philip; Cruzat, Vinicius Fernandes; Tirapegui, Julio

2016-08-01

We evaluated the effects of chronic oral supplementation with l-glutamine and l-alanine in their free form or as the dipeptide l-alanyl-l-glutamine (DIP) on muscle damage, inflammation and cytoprotection, in rats submitted to progressive resistance exercise (RE). Wistar rats (n 8/group) were submitted to 8-week RE, which consisted of climbing a ladder with progressive loads. In the final 21 d before euthanasia, supplements were delivered in a 4 % solution in drinking water. Glutamine, creatine kinase (CK), lactate dehydrogenase (LDH), TNF-α, specific IL (IL-1β, IL-6 and IL-10) and monocyte chemoattractant protein-1 (MCP-1) levels were evaluated in plasma. The concentrations of glutamine, TNF-α, IL-6 and IL-10, as well as NF-κB activation, were determined in extensor digitorum longus (EDL) skeletal muscle. HSP70 level was assayed in EDL and peripheral blood mononuclear cells (PBMC). RE reduced glutamine concentration in plasma and EDL (P<0·05 v. sedentary group). However, l-glutamine supplements (l-alanine plus l-glutamine (GLN+ALA) and DIP groups) restored glutamine levels in plasma (by 40 and 58 %, respectively) and muscle (by 93 and 105 %, respectively). GLN+ALA and DIP groups also exhibited increased level of HSP70 in EDL and PBMC, consistent with the reduction of NF-κB p65 activation and cytokines in EDL. Muscle protection was also indicated by attenuation in plasma levels of CK, LDH, TNF-α and IL-1β, as well as an increase in IL-6, IL-10 and MCP-1. Our study demonstrates that chronic oral l-glutamine treatment (given with l-alanine or as dipeptide) following progressive RE induces cyprotective effects mediated by HSP70-associated responses to muscle damage and inflammation.

Frequent Questions about e-Manifest

EPA Pesticide Factsheets

Frequently Asked Questions (FAQ) about e-Manifest covering these areas: scope, generators, receivers, manifest preparation & brokers, federal and state implementation, fee obligations, record retention, data policy, data correction, and user registration.

Chemical study, antioxidant, anti-hypertensive, and cytotoxic/cytoprotective activities of Centaurea cyanus L. petals aqueous extract.

PubMed

Escher, Graziela Bragueto; Santos, Jânio Sousa; Rosso, Neiva Deliberali; Marques, Mariza Boscacci; Azevedo, Luciana; do Carmo, Mariana Araújo Vieira; Daguer, Heitor; Molognoni, Luciano; Prado-Silva, Leonardo do; Sant'Ana, Anderson S; da Silva, Marcia Cristina; Granato, Daniel

2018-05-19

This study aimed to optimise the experimental conditions of extraction of the phytochemical compounds and functional properties of Centaurea cyanus petals. The following parameters were determined: the chemical composition (LC-ESI-MS/MS), the effects of pH on the stability and antioxidant activity of anthocyanins, the inhibition of lipid peroxidation, antioxidant activity, anti-hemolytic activity, antimicrobial, anti-hypertensive, and cytotoxic/cytoprotective effect, and the measurements of intracellular reactive oxygen species. Results showed that the temperature and time influenced (p ≤ 0.05) the content of flavonoids, anthocyanins, and FRAP. Only the temperature influenced the total phenolic content, non-anthocyanin flavonoids, and antioxidant activity (DPPH). The statistical approach made it possible to obtain the optimised experimental extraction conditions to increase the level of bioactive compounds. Chlorogenic, caffeic, ferulic, and p-coumaric acids, isoquercitrin, and coumarin were identified as the major compounds in the optimised extract. The optimised extract presented anti-hemolytic and anti-hypertensive activity in vitro, in addition to showing stability and reversibility of anthocyanins and antioxidant activity with pH variation. The C. cyanus petals aqueous extract exhibited high IC 50 and GI 50 (>900 μg/mL) values for all cell lines, meaning low cytotoxicity. Based on the stress oxidative assay, the extract exhibited pro-oxidant action (10-100 μg/mL) but did not cause damage or cell death. Copyright © 2018 Elsevier Ltd. All rights reserved.

40 CFR 262.25 - Electronic manifest signatures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Electronic manifest signatures. 262.25... (CONTINUED) STANDARDS APPLICABLE TO GENERATORS OF HAZARDOUS WASTE The Manifest § 262.25 Electronic manifest signatures. Electronic signature methods for the e-Manifest system shall: (a) Be a legally valid and...

40 CFR 761.210 - Manifest discrepancies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROHIBITIONS PCB Waste Disposal Records and Reports § 761.210 Manifest discrepancies. (a) Manifest discrepancies are differences between the quantity or type of PCB waste designated on the manifest or shipping paper and the quantity or type of PCB waste actually delivered to and received by a designated facility...

Idiopathic Pulmonary Fibrosis: Diagnosis and Clinical Manifestations

PubMed Central

Nakamura, Yutaro; Suda, Takafumi

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is a parenchymal lung disease characterized by progressive interstitial fibrosis. The clinical course of IPF can be unpredictable and may be punctuated by acute exacerbations. Although much progress is being made in unraveling the mechanisms underlying IPF, effective therapy for improving survival remains elusive. Longitudinal disease profiling, especially in terms of clinical manifestations in a large cohort of patients, should lead to proper management of the patients and development of new treatments for IPF. Appropriate multidisciplinary assessment in ongoing registries is required to achieve this. This review summarizes the current status of the diagnosis and clinical manifestations of IPF. PMID:27625576

Effects of Vedolizumab Therapy on Extraintestinal Manifestations in Inflammatory Bowel Disease.

PubMed

Fleisher, Mark; Marsal, Jan; Lee, Scott D; Frado, Laura E; Parian, Alyssa; Korelitz, Burton I; Feagan, Brian G

2018-04-01

Approximately 15-20% of ulcerative colitis patients and 20-40% of those with Crohn's disease experience extraintestinal manifestations (EIMs) of their inflammatory bowel disease (IBD). Clinicians who treat IBD must manage EIMs affecting multiple organs that variably correlate with intestinal disease activity. Vedolizumab is a monoclonal antibody for the treatment of IBD with a gut-selective mechanism of action. This report evaluates whether vedolizumab is an effective treatment of EIMs, given its gut-specific mechanism of action. We report 8 case studies of patients with various EIMs, including pyoderma gangrenosum, peripheral arthralgia/arthritis, axial arthropathies, erythema nodosum, and uveitis, who received vedolizumab therapy. Vedolizumab therapy was effective for pyoderma gangrenosum in ulcerative colitis, uveitis, erythema nodosum, polyarticular arthropathy, and ankylosing spondylitis/sacroiliitis but did not provide sustained benefit for the treatment of pyoderma gangrenosum in a patient with Crohn's disease. These cases demonstrate the potential of vedolizumab as a treatment of EIMs in patients with IBD.

Gastrointestinal Manifestations of Cystic Fibrosis

PubMed Central

2016-01-01

Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis. PMID:27330503

Effects of heat shock, stannous chloride, and gallium nitrate on the rat inflammatory response

PubMed Central

House, S.D.; Guidon, P.T.; Perdrizet, G.A.; Rewinski, M.; Kyriakos, R.; Bockman, R.S.; Mistry, T.; Gallagher, P.A.; Hightower, L.E.

2001-01-01

Heat and a variety of other stressors cause mammalian cells and tissues to acquire cytoprotection. This transient state of altered cellular physiology is nonproliferative and antiapoptotic. In this study, male Wistar rats were stress conditioned with either stannous chloride or gallium nitrate, which have immunosuppressive effects in vivo and in vitro, or heat shock, the most intensively studied inducer of cytoprotection. The early stages of inflammation in response to topical suffusion of mesentery tissue with formyl-methionyl-leucyl-phenylalanine (FMLP) were monitored using intravital microscopy. Microvascular hemodynamics (venular diameter, red blood cell velocity [Vrbc], white blood cell [WBC] flux, and leukocyte-endothelial adhesion [LEA]) were used as indicators of inflammation, and tissue levels of inducible Hsp70, determined using immunoblot assays, provided a marker of cytoprotection. None of the experimental treatments blocked decreases in WBC flux during FMLP suffusion, an indicator of increased low-affinity interactions between leukocytes and vascular endothelium known as rolling adhesion. During FMLP suffusion LEA, an indicator of firm attachment between leukocytes and vascular endothelial cells increased in placebo and gallium nitrate-treated animals but not in heat- and stannous chloride–treated animals, an anti-inflammatory effect. Hsp70 was not detected in aortic tissue from placebo and gallium nitrate–treated animals, indicating that Hsp70-dependent cytoprotection was not present. In contrast, Hsp70 was detected in aortic tissues from heat- and stannous chloride–treated animals, indicating that these tissues were in a cytoprotected state that was also an anti-inflammatory state. PMID:11599578

Cutaneous manifestations of Prototheca infections.

PubMed

Boyd, A S; Langley, M; King, L E

1995-05-01

The genus Prototheca comprises several species, the most prevalent of which is Prototheca wickerhamii. These achlorophyllic algae are found in the slime flux of trees and in freshwater environs. Cutaneous infection with these microbes was first reported 30 years ago. Subsequent case reports have described other manifestations including systemic disease. Asymptomatic and stationary cutaneous plaques may be seen in otherwise healthy patients. Susceptibility to infection is ill defined but may involve an inability of neutrophils to effectively eradicate phagocytosed organisms. Characteristic morula are seen histologically. Antifungal medications are the most effective therapy.

[Lyme disease--clinical manifestations and treatment].

PubMed

Stock, Ingo

2016-05-01

Lyme disease (Lyme borreliosis) is a systemic infectious disease that can present in a variety of clinical manifestations. The disease is caused by a group of spirochaetes--Borrelia burgdorferi sensu lato or Lyme borrelia--that are transmitted to humans by the bite of Ixodes ticks. Lyme disease is the most common arthropode-borne infectious disease in many European countries including Germany. Early localized infection is typically manifested by an erythema migrans skin lesion, in rarer cases as a borrelial lymphocytoma. The most common early disseminated manifestation is (early) neuroborreliosis. In adults, neuroborreliosis appears typically as meningoradiculoneuritis. Neuroborreliosis in children, however, is typically manifested by meningitis. In addition, multiple erythema migrans lesions and Lyme carditis occur relatively frequently. The most common manifestation oflate Lyme disease is Lyme arthritis. Early manifestations (and usually also late manifestations) of Lyme disease can be treated successfully by application of suitable antibacterial agents. For the treatment of Lyme disease, doxycycline, certain penicillins such as amoxicillin and some cephalosporins (ceftriaxone, cefotaxime, cefuroxime axetil) are recommended in current guidelines. A major challenge is the treatment of chronic, non-specific disorders, i. e., posttreatment Lyme disease syndrome and "chronic Lyme disease". Prevention of Lyme disease is mainly accomplished by protecting against tick bites. Prophylactic administration of doxycycline after tick bites is generally not recommended in Germany. There is no vaccine available for human beings.

Cytoprotective Polyphenols Against Chronological Skin Aging and Cutaneous Photodamage.

PubMed

Davinelli, Sergio; Bertoglio, Juan Carlos; Polimeni, Ascanio; Scapagnini, Giovanni

2018-01-01

Skin aging is a complex biological process influenced by a combination of intrinsic and extrinsic factors, leading to cumulative alterations of skin structure, function and appearance. Polyphenols, which are secondary plant metabolites, represent one of the largest classes of compounds used in dermatology and nutricosmetics to combat skin aging. The main objective is to provide an overview of the existing literature linking skin aging and the ability of polyphenols as regulatory elements able to maintain skin homeostasis. In this review, we discuss recent progress in understanding the molecular bases of skin aging, with specific emphasis on some well known and extensively studied polyphenols which have significant anti-aging influences and photoprotective effects. Although no relevant clinical data exist and standard delivery systems have not been established, promising results have been obtained in many in vitro and animal models. A wide variety of polyphenols may minimize mechanisms underlying the functional manifestations of photoaging and chronological skin aging. Polyphenols exert their influence mostly through their antioxidant and anti-inflammatory effects, thereby abrogating collagen degradation and/or increasing procollagen synthesis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

78 FR 11877 - Announcement of Requirements Gathering Meetings for the Electronic Manifest (e-Manifest) System

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-20

... Gathering Meetings for the Electronic Manifest (e-Manifest) System AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of public meetings. SUMMARY: EPA's Office of Resource Conservation and Recovery...'') system to capture information regarding the shipment of hazardous waste from the time it leaves the...

Anti-inflammatory, antiproliferative, and cytoprotective activity of NO chimera nitrates of use in cancer chemoprevention.

PubMed

Hagos, Ghenet K; Abdul-Hay, Samer O; Sohn, Johann; Edirisinghe, Praneeth D; Chandrasena, R Esala P; Wang, Zhiqiang; Li, Qian; Thatcher, Gregory R J

2008-11-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown promise in colorectal cancer (CRC), but they are compromised by gastrotoxicity. NO-NSAIDs are hybrid nitrates conjugated to an NSAID designed to exploit the gastroprotective properties of NO bioactivity. The NO chimera ethyl 2-((2,3-bis(nitrooxy)propyl)disulfanyl)benzoate (GT-094), a novel nitrate containing an NSAID and disulfide pharmacophores, is effective in vivo in rat models of CRC and is a lead compound for design of agents of use in CRC. Preferred chemopreventive agents possess 1) antiproliferative and 2) anti-inflammatory actions and 3) the ability to induce cytoprotective phase 2 enzymes. To determine the contribution of each pharmacophore to the biological activity of GT-094, these three biological activities were studied in vitro in compounds that deconstructed the structural elements of the lead GT-094. The anti-inflammatory and antiproliferative actions of GT-094 in vivo were recapitulated in vitro, and GT-094 was seen to induce phase 2 enzymes via the antioxidant responsive element. In the variety of colon, macrophage-like, and liver cell lines studied, the evidence from structure-activity relationships was that the disulfide structural element of GT-094 is the dominant contributor in vitro to the anti-inflammatory activity, antiproliferation, and enzyme induction. The results provide a direction for lead compound refinement. The evidence for a contribution from the NO mimetic activity of nitrates in vitro was equivocal, and combinations of nitrates with acetylsalicylic acid were inactive.

40 CFR 263.25 - Electronic manifest signatures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Electronic manifest signatures. 263.25 Section 263.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES... Recordkeeping § 263.25 Electronic manifest signatures. (a) Electronic manifest signatures shall meet the...

Cutaneous Manifestations of Crohn Disease.

PubMed

Hagen, Joshua W; Swoger, Jason M; Grandinetti, Lisa M

2015-07-01

Awareness of the extraintestinal manifestations of Crohn disease is increasing in dermatology and gastroenterology, with enhanced identification of entities that range from granulomatous diseases recapitulating the underlying inflammatory bowel disease to reactive conditions and associated dermatoses. In this review, the underlying etiopathology of Crohn disease is discussed, and how this mirrors certain skin manifestations that present in a subset of patients is explored. The array of extraintestinal manifestations that do not share a similar pathology, but which are often seen in association with inflammatory bowel disease, is also discussed. Treatment and pathogenetic mechanisms, where available, are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical manifestations of sleep apnea

PubMed Central

2015-01-01

Obstructive sleep apnea (OSA) may manifest in a number of ways from subtle intrusion into daily life to profound sleepiness, snoring, witnessed apneas and other classic symptoms. Although there is increasing evidence suggesting OSA can adversely affect health in a variety of ways, this disorder remains underdiagnosed. The most well-escribed health consequences of OSA relate to the cardiovascular system. Hypertension and arrhythmias have a strong association with OSA, and evidence suggests that treatment of OSA in patients with refractory hypertension and in patients planning cardioversion for atrial fibrillation may be of particularly importance. Significant associations between heart failure and OSA as well as complex sleep apnea have also been well-described. Cerebrovascular insult, impaired neurocognition, and poorly controlled mood disorder are also associated with in OSA. Therapy for OSA may ameliorate atherosclerotic progression and improve outcomes post-cerebrovascular accident (CVA). OSA should be considered in patients complaining of poor concentration at work, actual or near-miss motor vehicle accidents, and patients with severe sleepiness as a component of their co-morbid mood disorders. The metabolic impact of OSA has also been studied, particularly in relation to glucose homeostasis. Also of interest is the potential impact OSA has on lipid metabolism. The adverse effect untreated OSA has on glucose tolerance and lipid levels has led to the suggestion that OSA is yet another constituent of the metabolic syndrome. Some of these metabolic derangements may be related to the adverse effects untreated OSA has on hepatic health. The cardiovascular, neurocognitive, and metabolic manifestations of OSA can have a significant impact on patient health and quality of life. In many instances, evidence exists that therapy not only improves outcomes in general, but also modifies the severity of co-morbid disease. To mitigate the long-term sequela of this disease

Manifestations of Lyme carditis.

PubMed

Kostić, Tomislav; Momčilović, Stefan; Perišić, Zoran D; Apostolović, Svetlana R; Cvetković, Jovana; Jovanović, Andriana; Barać, Aleksandra; Šalinger-Martinović, Sonja; Tasić-Otašević, Suzana

2017-04-01

The first data of Lyme carditis, a relatively rare manifestation of Lyme disease, were published in eighties of the last century. Clinical manifestations include syncope, light-headedness, fainting, shortness of breath, palpitations, and/or chest pain. Atrioventricular (AV) electrical block of varying severity presents the most common conduction disorder in Lyme carditis. Although is usually mild, AV block can fluctuates rapidly and progress from a prolonged P-R interval to a His-Purkinje block within minutes to hours and days. Rarely, Lyme disease may be the cause of endocarditis, while some studies and reports, based on serological and/or molecular investigations, have suggested possible influence of Borrelia burgdorferi on degenerative cardiac valvular disease. Myocarditis, pericarditis, pancarditis, dilated cardiomyopathy, and heart failure have also been described as possible manifestations of Lyme carditis. The clinical course of Lyme carditis is generally mild, short term, and in most cases, completely reversible after adequate antibiotic treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

19 CFR 122.48 - Air cargo manifest.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Air cargo manifest. 122.48 Section 122.48 Customs... AIR COMMERCE REGULATIONS Aircraft Entry and Entry Documents; Electronic Manifest Requirements for..., and Overflying the United States § 122.48 Air cargo manifest. (a) When required. Except as provided in...

19 CFR 122.48 - Air cargo manifest.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Air cargo manifest. 122.48 Section 122.48 Customs... AIR COMMERCE REGULATIONS Aircraft Entry and Entry Documents; Electronic Manifest Requirements for..., and Overflying the United States § 122.48 Air cargo manifest. (a) When required. Except as provided in...

19 CFR 122.48 - Air cargo manifest.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Air cargo manifest. 122.48 Section 122.48 Customs... AIR COMMERCE REGULATIONS Aircraft Entry and Entry Documents; Electronic Manifest Requirements for..., and Overflying the United States § 122.48 Air cargo manifest. (a) When required. Except as provided in...

19 CFR 122.48 - Air cargo manifest.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Air cargo manifest. 122.48 Section 122.48 Customs... AIR COMMERCE REGULATIONS Aircraft Entry and Entry Documents; Electronic Manifest Requirements for..., and Overflying the United States § 122.48 Air cargo manifest. (a) When required. Except as provided in...

Anti-inflammatory and cytoprotective effects of a squalene synthase inhibitor, TAK-475 active metabolite-I, in immune cells simulating mevalonate kinase deficiency (MKD)-like condition.

PubMed

Suzuki, Nobutaka; Ito, Tatsuo; Matsui, Hisanori; Takizawa, Masayuki

2016-01-01

TAK-475 (lapaquistat acetate) and its active metabolite-I (TAK-475 M-I) inhibit squalene synthase, which catalyzes the conversion of farnesyl diphosphate (FPP) to squalene. FPP is a substrate for synthesis of other mevalonate-derived isoprenoids (MDIs) such as farnesol (FOH), geranlygeranyl diphosphate (GGPP), and geranylgeraniol. In patients with MKD, a rare autosomal recessive disorder, defective activity of mevalonate kinase leads to a shortage of MDIs. MDIs especially GGPP are required for prenylation of proteins, which is a posttranslation modification necessary for proper functioning of proteins like small guanosine triphosphatases. Malfunction of prenylation of proteins results in upregulation of the inflammatory cascade, leading to increased production of proinflammatory cytokines like interleukin-1β (IL-1β), eventually leading to episodic febrile attacks. In vitro, TAK-475 M-I incubation in a concentration dependent manner increased levels of FPP, GGPP, and FOH in human monocytic THP-1 cells. In subsequent experiments, THP-1 cells or human peripheral blood mononuclear cells (PBMCs) were incubated with simvastatin, which inhibits hydroxymethylglutaryl-coenzyme A reductase and thereby decreases levels of the precursors of MDIs, leading to the depletion of MDIs as expected in MKD patients. Increased levels of GGPP and FPP attenuated lipopolysaccharide (LPS)-induced IL-1β production in THP-1 cells and human PBMCs in statin-treated conditions. The MDIs also significantly reduced the damaged cell ratio in this active MKD-like condition. Moreover, TAK-475 M-I directly inhibited LPS-induced IL-1β production from statin-treated THP-1 cells. These results show anti-inflammatory and cytoprotective effects of MDIs via TAK-475 M-I treatment in statin-treated immune cells, suggesting that possible therapeutic effects of TAK-475 treatment in MKD patients.

49 CFR 176.30 - Dangerous cargo manifest.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false Dangerous cargo manifest. 176.30 Section 176.30... Requirements § 176.30 Dangerous cargo manifest. (a) The carrier, its agents, and any person designated for this purpose by the carrier or agents shall prepare a dangerous cargo manifest, list, or stowage plan. This...

49 CFR 176.30 - Dangerous cargo manifest.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Dangerous cargo manifest. 176.30 Section 176.30... Requirements § 176.30 Dangerous cargo manifest. (a) The carrier, its agents, and any person designated for this purpose by the carrier or agents must prepare a dangerous cargo manifest, list, or stowage plan. This...

49 CFR 176.30 - Dangerous cargo manifest.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Dangerous cargo manifest. 176.30 Section 176.30... Requirements § 176.30 Dangerous cargo manifest. (a) The carrier, its agents, and any person designated for this purpose by the carrier or agents shall prepare a dangerous cargo manifest, list, or stowage plan. This...

49 CFR 176.30 - Dangerous cargo manifest.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Dangerous cargo manifest. 176.30 Section 176.30... Requirements § 176.30 Dangerous cargo manifest. (a) The carrier, its agents, and any person designated for this purpose by the carrier or agents must prepare a dangerous cargo manifest, list, or stowage plan. This...

Surgical Treatment of Extraesophageal Manifestations of Gastroesophageal Reflux Disease.

PubMed

Sidwa, Feroze; Moore, Alessandra L; Alligood, Elaine; Fisichella, P Marco

2017-10-01

To review the current literature on the role of antireflux surgery (ARS) for the treatment of extraesophageal manifestations of GERD. The extraesophageal manifestations of gastroesophageal reflux disease (GERD) include chronic cough, laryngopharyngeal reflux, and asthma. They are responsible for significant morbidity in affected patients and a high economic burden on healthcare resources. We recently published a larger review on the symptoms, diagnosis, medical, and surgical treatment of the extraesophageal manifestations of GERD. Through our investigation, we found that the role of ARS for respiratory symptoms was unclear. Hence, we resorted through the data of our previous meta-analysis to compile a comprehensive and focused review on the role of ARS for respiratory symptoms. Using the archive of our previous meta-analysis, we selected studies extracted from the MEDLINE, Cochran, PubMed, Google Scholar, and Embase databases pertaining to the surgical treatment of extraesophageal manifestations of reflux (cough laryngopharyngeal reflux, and asthma). We applied a similar reporting methodology as was used in our previous manuscript and then hand searched the bibliographies of included studies yielding a total of 27 articles for review. We graded the level of evidence and classified recommendations by size of treatment effect per the American Heart Association Task Force on Practice Guidelines. Observational data indicated that syndromes of chronic cough, laryngopharyngeal reflux and asthma might improve after antireflux surgery only in highly selected patients-likely those with non-acid reflux-while those patients with objective markers of asthma severity do not. Because of the varied methods of diagnosis and surgical technique, non-comparative observational data may be unreliable. Additionally, our search found no randomized controlled trials (RCTs) comparing antireflux surgery to medical therapy in the treatment of cough or laryngopharyngeal reflux. One RCT

Evaluation of antioxidant and cytoprotective activities of Arnica montana L. and Artemisia absinthium L. ethanolic extracts

PubMed Central

2012-01-01

Background Arnica montana L. and Artemisia absinthium L. (Asteraceae) are medicinal plants native to temperate regions of Europe, including Romania, traditionally used for treatment of skin wounds, bruises and contusions. In the present study, A. montana and A. absinthium ethanolic extracts were evaluated for their chemical composition, antioxidant activity and protective effect against H2O2-induced oxidative stress in a mouse fibroblast-like NCTC cell line. Results A. absinthium extract showed a higher antioxidant capacity than A. montana extract as Trolox equivalent antioxidant capacity, Oxygen radical absorbance capacity and 2,2-diphenyl-1-picrylhydrazyl free radical-scavenging activity, in correlation with its flavonoids and phenolic acids content. Both plant extracts had significant effects on the growth of NCTC cells in the range of 10–100 mg/L A. montana and 10–500 mg/L A. absinthium. They also protected fibroblast cells against hydrogen peroxide-induced oxidative damage, at the same doses. The best protection was observed in cell pre-treatment with 10 mg/L A. montana and 10–300 mg/L A. absinthium, respectively, as determined by Neutral red and lactate dehydrogenase assays. In addition, cell pre-treatment with plant extracts, at these concentrations, prevented morphological changes induced by hydrogen peroxide. Flow-cytometry analysis showed that pre-treatment with A. montana and A. absinthium extracts restored the proportion of cells in each phase of the cell cycle. Conclusions A. montana and A. absinthium extracts, rich in flavonoids and phenolic acids, showed a good antioxidant activity and cytoprotective effect against oxidative damage in fibroblast-like cells. These results provide scientific support for the traditional use of A. montana and A. absinthium in treatment of skin disorders. PMID:22958433

Reliability and minimal detectable change of physical performance measures in individuals with pre-manifest and manifest Huntington disease.

PubMed

Quinn, Lori; Khalil, Hanan; Dawes, Helen; Fritz, Nora E; Kegelmeyer, Deb; Kloos, Anne D; Gillard, Jonathan W; Busse, Monica

2013-07-01

Clinical intervention trials in people with Huntington disease (HD) have been limited by a lack of reliable and appropriate outcome measures. The purpose of this study was to determine the reliability and minimal detectable change (MDC) of various outcome measures that are potentially suitable for evaluating physical functioning in individuals with HD. This was a multicenter, prospective, observational study. Participants with pre-manifest and manifest HD (early, middle, and late stages) were recruited from 8 international sites to complete a battery of physical performance and functional measures at 2 assessments, separated by 1 week. Test-retest reliability (using intraclass correlation coefficients) and MDC values were calculated for all measures. Seventy-five individuals with HD (mean age=52.12 years, SD=11.82) participated in the study. Test-retest reliability was very high (>.90) for participants with manifest HD for the Six-Minute Walk Test (6MWT), 10-Meter Walk Test, Timed "Up & Go" Test (TUG), Berg Balance Scale (BBS), Physical Performance Test (PPT), Barthel Index, Rivermead Mobility Index, and Tinetti Mobility Test (TMT). Many MDC values suggested a relatively high degree of inherent variability, particularly in the middle stage of HD. Minimum detectable change values for participants with manifest HD that were relatively low across disease stages were found for the BBS (5), PPT (5), and TUG (2.98). For individuals with pre-manifest HD (n=11), the 6MWT and Four Square Step Test had high reliability and low MDC values. The sample size for the pre-manifest HD group was small. The BBS, PPT, and TUG appear most appropriate for clinical trials aimed at improving physical functioning in people with manifest HD. Further research in people with pre-manifest HD is necessary.

40 CFR 761.210 - Manifest discrepancies.

Code of Federal Regulations, 2011 CFR

2011-07-01

... PROHIBITIONS PCB Waste Disposal Records and Reports § 761.210 Manifest discrepancies. (a) Manifest... commercial storage or disposal facility shall attempt to reconcile the discrepancy with the waste generator... Section 761.210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES...

40 CFR 761.210 - Manifest discrepancies.

Code of Federal Regulations, 2012 CFR

2012-07-01

... PROHIBITIONS PCB Waste Disposal Records and Reports § 761.210 Manifest discrepancies. (a) Manifest... commercial storage or disposal facility shall attempt to reconcile the discrepancy with the waste generator... Section 761.210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES...

Paradoxical articular manifestations in patients with inflammatory bowel diseases treated with infliximab.

PubMed

Thiebault, Henri; Boyard-Lasselin, Pauline; Guignant, Caroline; Guillaume, Nicolas; Wacrenier, Adrien; Sabbagh, Charles; Rebibo, Lionel; Brazier, Franck; Meynier, Jonathan; Nguyen-Khac, Eric; Dupas, Jean-Louis; Goëb, Vincent; Fumery, Mathurin

2016-08-01

-TNF because of the articular manifestations. Methotrexate was effective on articular symptoms in two of the three treated patients with paradoxical manifestations. No clinical or biological factors, including IFX trough levels, were associated with the occurrence of paradoxical manifestations. Paradoxical articular manifestations in IBD patients treated by anti-TNF are common, affecting more than 10% of patients. These events are generally mild and do not need discontinuation of anti-TNF therapy.

[Neurological manifestations of Whipple disease].

PubMed

Vital Durand, D; Gérard, A; Rousset, H

2002-10-01

Whipple disease is an uncommon chronic bacterial infection due to Tropheryma whipplei. Clinical manifestations are protean (joint pain, fever, weight loss, abdominal pain, lymphadenopathies), and the diagnosis is often delayed. Although previously considered a late manifestation of Whipple disease, neurological involvement is now frequently the initial clinical manifestation and represents the greatest risk for long-term disability. All patients should be treated and monitored as if they had central nervous system disease even if they are asymptomatic. Neurological manifestations include dementia (56 percent), abnormalities of eye movements (33p. cent), involuntary movements (28 percent), seizures, hypothalamic dysfunction, myelopathy, ataxia and psychiatric manifestations. Uveitis, retinitis, optic neuritis and papilloedema may be found. 80 percent of the reported cases of neuro-Whipple had associated systemic symptoms or signs but many patients are presenting without concurrent intestinal manifestation. Thus, the disease may remain undiagnosed or misdiagnosed, as rheumatoid arthritis or sarcoidosis. Traditionally, the diagnostic procedure of choice is biopsy of the duodenal mucosa by demonstrating PAS-positive foamy macrophages. However, not all cases have small bowel infiltration and tissue obtained from sites clinically affected may be helpful. CT and MR images of the central nervous system are normal or not specific: atrophic changes, mass lesions, focal abnormalities and hydrocephalus. The application of a PCR assay against Tropheryma whipplei has transformed the diagnosis. Positive results have been obtained from several tissues and from CSF and PCR is more sensitive than other techniques. All patients must be treated with antibiotics which cross the blood-brain barrier. Most agree that initial treatment with a combination of parenteral penicillin and streptomycin for at least 14 days is appropriate, thereafter cotrimoxazole orally 3 times a day for at least

Frequent Questions about the Manifest Registry

EPA Pesticide Factsheets

FAQs Including Can I submit multiple form samples to the EPA Registry for approval? Must I submit a continuation sheet sample to the Manifest Registry under section 262.21(d)? Can I typeset the form after I am approved to print the manifest?

40 CFR 264.72 - Manifest discrepancies.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 264.72 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Manifest... waste acid, or toxic constituents not reported on the manifest or shipping paper. (c) Upon discovering a...

40 CFR 264.72 - Manifest discrepancies.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 264.72 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Manifest... waste acid, or toxic constituents not reported on the manifest or shipping paper. (c) Upon discovering a...

40 CFR 264.72 - Manifest discrepancies.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 264.72 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Manifest... waste acid, or toxic constituents not reported on the manifest or shipping paper. (c) Upon discovering a...

40 CFR 264.72 - Manifest discrepancies.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 264.72 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Manifest... waste acid, or toxic constituents not reported on the manifest or shipping paper. (c) Upon discovering a...

40 CFR 264.72 - Manifest discrepancies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 264.72 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Manifest... waste acid, or toxic constituents not reported on the manifest or shipping paper. (c) Upon discovering a...

Disease-related and drug-induced skin manifestations in inflammatory bowel disease.

PubMed

Hindryckx, Pieter; Novak, Gregor; Costanzo, Antonio; Danese, Silvio

2017-03-01

Skin manifestations are common in patients with inflammatory bowel diseases (IBD) and can be part of a concomitant illness with a shared genetic background, an extra-intestinal manifestation of the disease, or a drug side-effect. Areas covered: We provide a practical overview of the epidemiology, pathogenesis, diagnosis, therapeutic approach and prognosis of the most frequent disease-related and drug-induced cutaneous manifestations in IBD, illustrated by cases encountered in our clinical practice. Among the most frequently encountered IBD-related lesions are erythema nodosum, pyoderma gangrenosum and Sweet's syndrome. Common skin manifestations with a strong association to TNF antagonists are local injection site reactions, psoriasiform lesions, cutaneous infections, vasculitides and lupus-like syndromes. In addition, we discuss the relation of thiopurines and TNF antagonists with the risk of skin cancer. Expert commentary: We hope this review will help caretakers involved in the management of IBD patients to recognize the lesions and to manage them in close collaboration with a dedicated dermatologist.

Oral Manifestations in Pediatric Patients with Coeliac Disease - A Review Article.

PubMed

Macho, Viviana Marisa Pereira; Coelho, Ana Sofia; Veloso E Silva, Diana Maria; de Andrade, David José Casimiro

2017-01-01

Coeliac disease is a chronic enteropathy that remains a challenge for the clinician, due to its atypical manifestations and etiopathogenic complexity. This article intends to describe the oral characteristics of Coeliac Disease in children in order to facilitate their management in the dental office. A review of the literature was performed electronically in PubMed (PubMed Central, and MEDLINE) for articles published in English from 2000 to April of 2017. The article is also based on the authors' clinical experience with children with coeliac disease. The searched keywords were "coeliac disease ","oral manifestations ", "dental enamel defects", "recurrent aphthous stomatitis" and "oral aphthous ulcers". There are some oral manifestations which are strictly related to coeliac disease: dental enamel defects, recurrent aphthous stomatitis, delayed tooth eruption, multiple caries, angular cheilitis, atrophic glossitis, dry mouth and burning tongue. The complete knowledge of the oral manifestations of coeliac disease can trigger an effective change in the quality of life of the patients with this disease.

40 CFR 262.23 - Use of the manifest.

Code of Federal Regulations, 2010 CFR

2010-07-01

... generation, the generator must send at least three copies of the manifest dated and signed in accordance with....72(f)), the generator must: (1) Sign either: (i) Item 20 of the new manifest if a new manifest is...

Paraneoplastic cutaneous manifestations: concepts and updates*

PubMed Central

da Silva, Josenilson Antônio; Mesquita, Kleyton de Carvalho; Igreja, Ana Carolina de Souza Machado; Lucas, Isabella Cristina Rodrigues Naves; Freitas, Aline Ferreira; de Oliveira, Sandra Maximiano; Costa, Izelda Maria Carvalho; Campbell, Iphis Tenfuss

2013-01-01

The skin often signals systemic changes. Some neoplastic diseases that affect internal organs may trigger several cutaneous manifestations. Although these dermatoses are relatively unusual, the recognition of some typical paraneoplastic dermatoses may lead to the early diagnosis of a neoplasm and determine a better prognosis. In this review article, we discuss the paraneoplastic cutaneous manifestations strongly associated with neoplasms, which include acanthosis nigricans maligna, tripe palms, erythema gyratum repens, Bazex syndrome, acquired hypertrichosis lanuginosa, necrolytic migratory erythema, Leser-Trélat sign and paraneoplastic pemphigus. We also review the clinical manifestations of each condition and include updated knowledge on disease pathogenesis. PMID:23538999

Comparative analysis of the role of small G proteins in cell migration and cell death: Cytoprotective and promigratory effects of RalA

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

Jeon, Hyejin; Zheng, Long Tai; Lee, Shinrye

2011-08-15

Small G protein superfamily consists of more than 150 members, and is classified into six families: the Ras, Rho, Rab, Arf, Ran, and RGK families. They regulate a wide variety of cell functions such as cell proliferation/differentiation, cytoskeletal reorganization, vesicle trafficking, nucleocytoplasmic transport and microtubule organization. The small G proteins have also been shown to regulate cell death/survival and cell shape. In this study, we compared the role of representative members of the six families of small G proteins in cell migration and cell death/survival, two cellular phenotypes that are associated with inflammation, tumorigenesis, and metastasis. Our results show thatmore » small G proteins of the six families differentially regulate cell death and cell cycle distribution. In particular, our results indicate that Rho family of small G proteins is antiapoptotic. Ras, Rho, and Ran families promoted cell migration. There was no significant correlation between the cell death- and cell migration-regulating activities of the small G proteins. Nevertheless, RalA was not only cytoprotective against multiple chemotherapeutic drugs, but also promigratory inducing stress fiber formation, which was accompanied by the activation of Akt and Erk pathways. Our study provides a framework for further systematic investigation of small G proteins in the perspectives of cell death/survival and motility in inflammation and cancer.« less

Altered brain mechanisms of emotion processing in pre-manifest Huntington's disease.

PubMed

Novak, Marianne J U; Warren, Jason D; Henley, Susie M D; Draganski, Bogdan; Frackowiak, Richard S; Tabrizi, Sarah J

2012-04-01

, right pallidum, right thalamus, cerebellum, middle frontal, middle occipital, right superior and left inferior temporal gyri, and left superior parietal lobule. The modulated happiness network included postcentral gyri, left caudate, right cingulate cortex, right superior and inferior parietal lobules, and right superior frontal, middle temporal, middle occipital and precentral gyri. These effects were not driven merely by striatal dysfunction. We did not find equivalent associations between brain structure and emotion recognition, and the pre-manifest Huntington's disease cohort did not have a behavioural deficit in out-of-scanner emotion recognition relative to controls. In addition, we found increased neural activity in the pre-manifest subjects in response to all three emotions in frontal regions, predominantly in the middle frontal gyri. Overall, these findings suggest that pathophysiological effects of Huntington's disease may precede the development of overt clinical symptoms and detectable cerebral atrophy.

Articular manifestations of familial hypercholesterolaemia.

PubMed Central

Mathon, G; Gagné, C; Brun, D; Lupien, P J; Moorjani, S

1985-01-01

Familial hypercholesterolaemia is characterised by a decreased removal of low density lipoproteins and premature coronary artery disease. Tendinous xanthomata are a hallmark of the disease. The affected joints may also be the sites of inflammation and pain. Arthropathy has been associated mainly with the homozygous form of familial hypercholesterolaemia, but it is also known to occur in the heterozygous form. We report on the articular manifestations in 73 patients with heterozygous familial hypercholesterolaemia. About 40% of these patients had at least one episode of articular symptoms. The observed articular manifestations may be classified into four types: Achilles pain (18%), Achilles tendinitis (11%), oligoarticular arthritis (7%), polyarticular or rheumatic fever-like arthritis (4%). It is concluded that in heterozygous familial hypercholesterolaemia articular manifestations are frequent, diverse, and may be the first symptom of this metabolic disorder. Images PMID:4037885

40 CFR 262.24 - Use of the electronic manifest.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) STANDARDS APPLICABLE TO GENERATORS OF HAZARDOUS WASTE The Manifest § 262.24 Use of the electronic... originated that all waste handlers named on the manifest participate in the electronic manifest system. (d... is unavailable. If a generator has prepared an electronic manifest for a hazardous waste shipment...

Dermatologic manifestations of endocrine disorders

PubMed Central

Lause, Michael; Kamboj, Alisha

2017-01-01

The skin serves as a window for clinicians to understand, diagnose, and monitor endocrine disease. Dermatologic manifestations of endocrinopathies contribute significantly to an individual’s health and quality of life. In this review, we outline various disorders of the hypothalamic-pituitary axis, thyroid gland, pancreas, adrenal gland, and androgen axis as well as hereditary endocrine syndromes. In acromegaly, glycosaminoglycan deposition contributes to a thickening of skin and soft tissue, which manifests as coarsening and enlargement of facial and acral structures. Stimulation of the thyrotropin receptor in hyperthyroidism results in mesenchymal tissue proliferation and consequent pretibial myxedema; other associated cutaneous features include onycholysis, and hyperhidrosis. Individuals with hypothyroidism exhibit cold, dry skin and brittle hair as well as a jaundice-like appearance due to carotene excess. The cutaneous features of diabetes mellitus (DM), mediated to a large extent by hyperglycemia and hyperinsulinemia, include necrobiosis lipoidica diabeticorum (NLD), diabetic dermopathy, and acanthosis nigricans. Pediatric patients with Cushing’s syndrome almost invariably present with truncal obesity and growth retardation; disruption of collagen formation and the catabolic effects of hypercortisolism result in skin atrophy and purple abdominal striae. In patients with Addison’s disease, generalized hyperpigmentation, secondary to elevated levels of melanocyte-stimulating hormone (MSH), is most prominent in sun-exposed areas. Due to hyperandrogenism, individuals with polycystic ovarian syndrome (PCOS) often exhibit hirsutism, acne vulgaris, and androgenetic alopecia. In multiple endocrine neoplasia (MEN) syndromes, specific gene mutations may lead to angiofibromas, lichen amyloidosis, and ganglioneuromas. Disruptions of immune regulation result in autoimmune polyglandular syndromes (APS) and associated clinical features including chronic mucocutaneous

Intracoronary Cytoprotective Gene Therapy: A Study of VEGF-B167 in a Pre-Clinical Animal Model of Dilated Cardiomyopathy.

PubMed

Woitek, Felix; Zentilin, Lorena; Hoffman, Nicholas E; Powers, Jeffery C; Ottiger, Isabel; Parikh, Suraj; Kulczycki, Anna M; Hurst, Marykathryn; Ring, Nadja; Wang, Tao; Shaikh, Farah; Gross, Polina; Singh, Harinder; Kolpakov, Mikhail A; Linke, Axel; Houser, Steven R; Rizzo, Victor; Sabri, Abdelkarim; Madesh, Muniswamy; Giacca, Mauro; Recchia, Fabio A

2015-07-14

Vascular endothelial growth factor (VEGF)-B activates cytoprotective/antiapoptotic and minimally angiogenic mechanisms via VEGF receptors. Therefore, VEGF-B might be an ideal candidate for the treatment of dilated cardiomyopathy, which displays modest microvascular rarefaction and increased rate of apoptosis. This study evaluated VEGF-B gene therapy in a canine model of tachypacing-induced dilated cardiomyopathy. Chronically instrumented dogs underwent cardiac tachypacing for 28 days. Adeno-associated virus serotype 9 viral vectors carrying VEGF-B167 genes were infused intracoronarily at the beginning of the pacing protocol or during compensated heart failure. Moreover, we tested a novel VEGF-B167 transgene controlled by the atrial natriuretic factor promoter. Compared with control subjects, VEGF-B167 markedly preserved diastolic and contractile function and attenuated ventricular chamber remodeling, halting the progression from compensated to decompensated heart failure. Atrial natriuretic factor-VEGF-B167 expression was low in normally functioning hearts and stimulated by cardiac pacing; it thus functioned as an ideal therapeutic transgene, active only under pathological conditions. Our results, obtained with a standard technique of interventional cardiology in a clinically relevant animal model, support VEGF-B167 gene transfer as an affordable and effective new therapy for nonischemic heart failure. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

46 CFR 148.72 - Dangerous cargo manifest; exceptions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Dangerous cargo manifest; exceptions. 148.72 Section 148.72 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES CARRIAGE OF... Dangerous cargo manifest; exceptions. (a) No dangerous cargo manifest is required for— (1) Shipments by...

46 CFR 148.72 - Dangerous cargo manifest; exceptions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Dangerous cargo manifest; exceptions. 148.72 Section 148.72 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES CARRIAGE OF... Dangerous cargo manifest; exceptions. (a) No dangerous cargo manifest is required for— (1) Shipments by...

46 CFR 148.72 - Dangerous cargo manifest; exceptions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Dangerous cargo manifest; exceptions. 148.72 Section 148.72 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES CARRIAGE OF... Dangerous cargo manifest; exceptions. (a) No dangerous cargo manifest is required for— (1) Shipments by...

46 CFR 148.72 - Dangerous cargo manifest; exceptions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Dangerous cargo manifest; exceptions. 148.72 Section 148.72 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES CARRIAGE OF... Dangerous cargo manifest; exceptions. (a) No dangerous cargo manifest is required for— (1) Shipments by...

The effect of job insecurity on employee health complaints: A within-person analysis of the explanatory role of threats to the manifest and latent benefits of work.

PubMed

Vander Elst, Tinne; Näswall, Katharina; Bernhard-Oettel, Claudia; De Witte, Hans; Sverke, Magnus

2016-01-01

The current study contributes to the literature on job insecurity by highlighting threat to the benefits of work as an explanation of the effect of job insecurity on health complaints. Building on the latent deprivation model, we predicted that threats to both manifest (i.e., financial income) and latent benefits of work (i.e., collective purpose, social contacts, status, time structure, activity) mediate the relationships from job insecurity to subsequent mental and physical health complaints. In addition, in line with the conservation of resources theory, we proposed that financial resources buffer the indirect effect of job insecurity on health complaints through threat to the manifest benefit. Hypotheses were tested using a multilevel design, in which 3 measurements (time lag of 6 months between subsequent measurements) were clustered within 1,994 employees (in Flanders, Belgium). This allowed for the investigation of within-person processes, while controlling for variance at the between-person level. The results demonstrate that job insecurity was related to subsequent threats to both manifest and latent benefits, and that these threats in turn were related to subsequent health complaints (with an exception for threat to the manifest benefit that did not predict mental health complaints). Three significant indirect effects were found: threat to the latent benefits mediated the relationships between job insecurity and both mental and physical health complaints, and threat to the manifest benefit mediated the relationship between job insecurity and physical health complaints. Unexpectedly, the latter indirect effect was exacerbated by financial resources. (c) 2016 APA, all rights reserved).

Antiulcerogenic effects of coconut (Cocos nucifera) extract in rats.

PubMed

Nneli, R O; Woyike, O A

2008-07-01

A warm water crude extract of coconut milk and a coconut water dispersion were investigated for their antiulcerogenic effects in male Wistar albino rats. Ulcers were induced in the male rats by subcutaneous administration of indomethacin (40 mg/kg) using standard procedures. The ulcer inhibition rate (UIR) was taken as a measure of the cytoprotection offered by test substances. Coconut milk (2 mL daily oral feeding) produced a stronger percentage (54%) reduction in the mean ulcer area than coconut water (39%). The effect of coconut milk was similar to the effect of sucralfate that reduced the mean ulcer area by 56% in this study. Sucralfate is a conventional cytoprotective agent. The results showed that coconut milk and water via macroscopic observation had protective effects on the ulcerated gastric mucosa. It is concluded that coconut milk offered stronger protection on indomethacin-induced ulceration than coconut water in rats.

40 CFR 265.71 - Use of manifest system.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the manifest; (iv) Within 30 days of delivery, send a copy of the manifest to the generator; and (v... Pennsylvania Avenue, NW., Washington, DC 20460. (b) If a facility receives, from a rail or water (bulk shipment... on the manifest (excluding the EPA identification numbers, generator's certification, and signatures...

e-Manifest for Hazardous Wastes in Texas

EPA Pesticide Factsheets

EPA launches the hazardous waste electronic manifest (e-Manifest) system on June 30, 2018. The fact sheets here are written from EPA's federal perspective but do contain useful information about Texas

e-Manifest for Hazardous Wastes in Arkansas

EPA Pesticide Factsheets

EPA launches the hazardous waste electronic manifest (e-Manifest) system on June 30, 2018. The fact sheets here are written from EPA's federal perspective but do contain useful information about Arkansas

e-Manifest for Hazardous Wastes in Louisiana

EPA Pesticide Factsheets

EPA launches the hazardous waste electronic manifest (e-Manifest) system on June 30, 2018. The fact sheets here are written from EPA's federal perspective but do contain useful information about Louisiana

e-Manifest for Hazardous Wastes in Oklahoma

EPA Pesticide Factsheets

EPA launches the hazardous waste electronic manifest (e-Manifest) system on June 30, 2018. The fact sheets here are written from EPA's federal perspective but do contain useful information about Oklahoma

Oral Manifestations of Secondary Syphilis.

PubMed

de Paulo, Luiz Fernando Barbosa; Servato, João Paulo Silva; Oliveira, Maiolino Thomaz Fonseca; Durighetto, Antonio Francisco; Zanetta-Barbosa, Darceny

2015-06-01

Known as "the great imitator," secondary syphilis may clinically manifest itself in myriad ways, involving different organs including the oral mucosa, and mimicking, both clinically and histologically, several diseases, thereby making diagnosis a challenge for clinicians. We highlight the clinical aspects of oral manifestation in 7 patients with secondary syphilis. Clinicians should consider secondary syphilis in the differential diagnosis of ulcerative and/or white oral lesions. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

21 CFR 11.50 - Signature manifestations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Signature manifestations. 11.50 Section 11.50 Food... RECORDS; ELECTRONIC SIGNATURES Electronic Records § 11.50 Signature manifestations. (a) Signed electronic...: (1) The printed name of the signer; (2) The date and time when the signature was executed; and (3...

Orofacial manifestations of scleroderma. A literature review.

PubMed

Hadj Said, M; Foletti, J M; Graillon, N; Guyot, L; Chossegros, C

2016-11-01

Scleroderma is a rare disease of the connective tissue (50 to 200 patients/1 million people; 60,000 patients in France). We conducted a literature review about the orofacial manifestations of scleroderma that have been little studied. The 45 articles found in 6 different databases by using the keywords "scleroderma", "systemic sclerosis", "oral medicine", "face" and published between 1944 and 2016 were selected, for a total of 328 patients. A total of 1187 orofacial manifestations of scleroderma were identified, occurring mainly in women (84.5%) with a mean age of 40.2 years, 10 years on average after the first manifestation of the disease. The main ones were limitation of mouth opening (69.8%), widening of the periodontal ligament (67.3%), xerostomia (63.4%), telangiectasia (36.2%) and bone lesions (34.5%). Dental root resorptions, pulp and nose calcifications were also reported but with no evident link with scleroderma. Orofacial manifestations of scleroderma are probably more common than reported. They mostly affect women with a mean age of 40. The most common oral manifestations are limitation of mouth opening, widening of the periodontal ligament and xerostomia. Because of the handicap they may be responsible for, these manifestations must be detected early in order to prevent from functional impairments and from dental and periodontal lesions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Cardiac manifestations of sarcoidosis: diagnosis and management.

PubMed

Birnie, David H; Kandolin, Riina; Nery, Pablo B; Kupari, Markku

2017-09-14

Approximately 5% of patients with sarcoidosis will have clinically manifest cardiac involvement presenting with one or more of ventricular arrhythmias, conduction abnormalities, and heart failure. Cardiac presentations can be the first (and/or an unrecognized) manifestation of sarcoidosis in a variety of circumstances. Cardiac symptoms are usually dominant over extra-cardiac as most patients with clinically manifest disease have minimal extra-cardiac disease and up to two-thirds have isolated cardiac sarcoidosis (CS). It is estimated that another 20-25% of pulmonary/systemic sarcoidosis patients have asymptomatic cardiac involvement (clinically silent disease). The extent of left ventricular dysfunction seems to be the most important predictor of prognosis among patients with clinically manifest CS. In addition, the extent of myocardial late gadolinium enhancement is emerging as an important prognostic factor. The literature shows some controversy regarding outcomes for patients with clinically silent CS and larger studies are needed. Immunosuppression therapy (usually with corticosteroids) has been suggested for the treatment of clinically manifest CS despite minimal data supporting it. Fluorodeoxyglucose Positron Emission Tomography imaging is often used to detect active disease and guide immunosuppression. Patients with clinically manifest disease often need device therapy, typically with implantable cardioverter defibrillators. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Autorefraction Versus Manifest Refraction in Patients With Keratoconus.

PubMed

Soeters, Nienke; Muijzer, Marc B; Molenaar, Jurrian; Godefrooij, Daniel A; Wisse, Robert P L

2018-01-01

To compare visual performance using autorefraction and manifest refraction assessments in patients with keratoconus and investigate whether autorefraction measurements lead to suboptimal visual performance. Corrected distance visual acuity (CDVA) was measured in 90 eyes of 61 patients with keratoconus with both autorefraction and manifest refraction, in a random order. Maximum keratometry (Kmax), cone location, and wavefront aberration were determined with Scheimpflug tomography. The difference between the autorefraction and manifest refraction outcomes was converted to vectors and a multivariable analysis was performed to identify potential underlying causes of this difference. A significantly better CDVA was achieved with manifest refraction (0.06 vs 0.29 logMAR [20/23 vs 20/38 Snellen], P < .001). After vector analysis, a mean difference of 4.83 diopters was found between autorefraction and manifest refraction. Increased Kmax was strongly and significantly associated with better visual performance of manifest refraction compared to autorefraction (B = 0.496, P = .002). This study showed that a superior CDVA is achieved with manifest refraction compared to autorefraction in patients with keratoconus. Furthermore, the difference between the two refraction methods increases as the cornea steepens. According to this study, autorefraction is unreliable in patients with keratoconus and should be avoided. [J Refract Surg. 2018;34(1):30-34.]. Copyright 2018, SLACK Incorporated.

Oral manifestation in inflammatory bowel disease: A review

PubMed Central

Lankarani, Kamran B; Sivandzadeh, Gholam Reza; Hassanpour, Shima

2013-01-01

Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis, not only affect the intestinal tract but also have an extraintestinal involvement within the oral cavity. These oral manifestations may assist in the diagnosis and the monitoring of disease activity, whilst ignoring them may lead to an inaccurate diagnosis and useless and expensive workups. Indurated tag-like lesions, cobblestoning, and mucogingivitis are the most common specific oral findings encountered in CD cases. Aphthous stomatitis and pyostomatitis vegetans are among non-specific oral manifestations of IBD. In differential diagnosis, side effects of drugs, infections, nutritional deficiencies, and other inflammatory conditions should also be considered. Treatment usually involves managing the underlying intestinal disease. In severe cases with local symptoms, topical and/or systemic steroids and immunosuppressive drugs might be used. PMID:24379574

[Thoracic manifestation of tuberculosis].

PubMed

Kienzl-Palma, D; Prosch, H

2016-10-01

Tuberculosis (TB) is a granulomatous disease caused by Mycobacterium tuberculosis and transmission is via an airborne route by droplet infection. In the majority of cases patients have thoracic TB, which most frequently presents with hilar lymphadenopathy and pulmonary manifestation. Due to the rise in incidence of TB in central Europe to be expected over the coming years, it is essential to be acquainted with the radiological manifestations of pulmonary TB, particularly to be able to discriminate active from inactive TB. Due to the use of molecular techniques entailing DNA fingerprinting, the traditional classification of TB in primary and postprimary TB is being challenged. These genetic studies have revealed that variations in the clinical and radiographic appearance of TB are mainly affected by the immune status of the patients. Due to the low prevalence of TB in central Europe and the wide variation of radiological presentations, the diagnosis and therapy of TB is often delayed. In this article, the radiographic manifestations of thoracic TB are summarized and discussed. Together with the medical history and bacteriological tests, chest X‑ray imaging and computed tomography (CT) play a major role not only in the detection of TB but also in the follow-up during and after therapy. Chest X‑radiographs should be the primary diagnostic method in patients with suspected TB in screening as well as for diagnosis and therapy monitoring. The use of CT is more sensitive than chest radiographs and is frequently performed after chest radiographs to obtain detailed information about subtle parenchymal changes or lymph node manifestation. When active TB is suspected CT should be performed. Tree in bud, lobular consolidations, centrilobular nodules, cavities and ground-glass opacification are typical changes in active TB.

Piper betle Induced Cytoprotective Genes and Proteins via the Nrf2/ARE Pathway in Aging Mice.

PubMed

Aliahmat, Nor Syahida; Abdul Sani, Nur Fathiah; Wan Hasan, Wan Nuraini; Makpol, Suzana; Wan Ngah, Wan Zurinah; Mohd Yusof, Yasmin Anum

2016-01-01

The objective of this study was to elucidate the underlying antioxidant mechanism of aqueous extract of Piper betle (PB) in aging rats. The nuclear factor erythroid 2-related factor 2 (Nrf2)/ARE pathway involving phase II detoxifying and antioxidant enzymes plays an important role in the antioxidant system by reducing electrophiles and reactive oxygen species through induction of phase II enzymes and proteins. Genes and proteins of phase II detoxifying antioxidant enzymes were analyzed by QuantiGenePlex 2.0 Assay and Western blot analysis. PB significantly induced genes and proteins of phase II and antioxidant enzymes, NAD(P)H quinone oxidoreductase 1, and catalase in aging mice (p < 0.05). The expression of these enzymes were stimulated via translocation of Nrf2 into the nucleus, indicating the involvement of ARE, a cis-acting motif located in the promoter region of nearly all phase II genes. PB was testified for the first time to induce cytoprotective genes through the Nrf2/ARE signaling pathway, thus unraveling the antioxidant mechanism of PB during the aging process. © 2016 S. Karger AG, Basel.

The role of glycolysis and gluconeogenesis in the cytoprotection of neuroblastoma cells against 1-methyl 4-phenylpyridinium ion toxicity.

PubMed

Mazzio, Elizabeth; Soliman, Karam F A

2003-01-01

1-Methyl-4-phenylpyridinium (MPP+) is a mitochondrial Complex I inhibitor and is frequently used to investigate the pathological degeneration of neurons associated with Parkinson's disease (PD). In vitro, extracellular concentration of glucose is one of the most critical factors in establishing the vulnerability of neurons to MPP+ toxicity. While glucose is the primary energy fuel for the brain, central nervous system (CNS) neurons can also take up and utilize other metabolic intermediates for energy. In this study, we compared various monosaccharides, disaccharides, nutritive/non-nutritive sugar alcohols, glycolytic and gluconeogenic metabolic intermediates for their cytoprotection against MPP+ in murine brain neuroblastoma cells. Several monosaccharides were effective against MMP+ (500 microM) including glucose, fructose and mannose, which restored cell viability to 109 +/- 5%, 70 +/- 5%, 99 +/- 3% of live controls, respectively. Slight protective effects were observed in the presence of 3-phosphoglyceric acid and glucose-6-phosphate; however, no protective effects were exhibited by galactose, sucrose, sorbitol, mannitol, glycerol or various gluconeogenic and ketogenic amino acids. On the other hand, fructose 1,6 bisphosphate and gluconeogenic energy intermediates [pyruvic acid, malic acid and phospho(enol)pyruvate (PEP)] were neuroprotective against MPP+. The gluconeogenic intermediates elevated intracellular levels of ATP and reduced propidium iodide (PI) nucleic acid staining to live controls, but did not alter the MPP(+)-induced loss of mitochondrial O2 consumption. These data indicate that malic acid, pyruvic acid and PEP contribute to anaerobic substrate level phosphorylation. The use of hydrazine sulfate to impede gluconeogenesis through PEP carboxykinase (PEPCK) inhibition heightened the protective effects of energy substrates possibly due to attenuated ATP demands from pyruvate carboxylase (PC) activity and pyruvate mitochondrial transport. It was

Orofacial manifestations of achondroplasia

PubMed Central

Rohilla, Smriti; Kaushik, Atul; Vinod, V.C.; Tanwar, Renu; Kumar, Munish

2012-01-01

Achondroplasia (Online Mendelian Inheritance in Man [OMIM] 100800), is considered as a form of skeletal dysplasia dwarfism that manifests with stunted stature and disproportionate limb shortening. Achondroplasia is of special interest in the field of dentistry because of its characteristic craniofacial features which include relative macrocephaly, depressed nasal bridge and maxillary hypoplasia. Presence of large head, implanted shunt, airway obstruction and difficulty in head control requires special precautions during dental management. The current case report highlights the orofacial manifestations of Achondroplasia in a young pediatric patient, along with the multidisciplinary treatment (including the dental treatment) done for the patient which also might help the general practitioners in better understanding of the condition. PMID:27298609

Gene Therapy for Neurologic Manifestations of Mucopolysaccharidoses

PubMed Central

Wolf, Daniel A.; Banerjee, Sharbani; Hackett, Perry B.; Whitley, Chester B.; McIvor, R. Scott; Low, Walter C.

2015-01-01

Introduction Mucopolysaccharidoses are a family of lysosomal disorders caused by mutations in genes that encode enzymes involved in the catabolism of glycoaminoglycans. These mutations affect multiple organ systems and can be particularly deleterious to the nervous system. At the present time, enzyme replacement therapy and hematopoietic stem-cell therapy are used to treat patients with different forms of these disorders. However, to a great extent the nervous system is not adequately responsive to current therapeutic approaches. Areas Covered Recent advances in gene therapy show great promise for treating mucopolysaccharidoses. This article reviews the current state of the art for routes of delivery in developing genetic therapies for treating the neurologic manifestations of mucopolysaccharidoses. Expert Opinion Gene therapy for treating neurological manifestations of mucopolysaccharidoses can be achieved by intraventricular, intrathecal, intranasal, and systemic administration. The intraventricular route of administration appears to provide the most wide-spread distribution of gene therapy vectors to the brain. The intrathecal route of delivery results in predominant distribution to the caudal areas of the brain while the intranasal route of delivery results in good distribution to the rostral areas of brain. The systemic route of delivery via intravenous delivery can also achieve wide spread delivery to the CNS, however, the distribution to the brain is greatly dependent on the vector system. Intravenous delivery using lentiviral vectors appear to be less effective than adeno-associated viral (AAV) vectors. Moreover, some subtypes of AAV vectors are more effective than others in crossing the blood-brain-barrier. In summary, the recent advances in gene vector technology and routes of delivery to the CNS will facilitate the clinical translation of gene therapy for the treatment of the neurological manifestations of mucopolysaccharidoses. PMID:25510418

Clinical Manifestations Associated with Neurocysticercosis: A Systematic Review

PubMed Central

Carabin, Hélène; Ndimubanzi, Patrick Cyaga; Budke, Christine M.; Nguyen, Hai; Qian, Yingjun; Cowan, Linda Demetry; Stoner, Julie Ann; Rainwater, Elizabeth; Dickey, Mary

2011-01-01

Background The clinical manifestations of neurocysticercosis (NCC) are poorly understood. This systematic review aims to estimate the frequencies of different manifestations, complications and disabilities associated with NCC. Methods A systematic search of the literature published from January 1, 1990, to June 1, 2008, in 24 different electronic databases and 8 languages was conducted. Meta-analyses were conducted when appropriate. Results A total of 1569 documents were identified, and 21 included in the analysis. Among patients seen in neurology clinics, seizures/epilepsy were the most common manifestations (78.8%, 95%CI: 65.1%–89.7%) followed by headaches (37.9%, 95%CI: 23.3%–53.7%), focal deficits (16.0%, 95%CI: 9.7%–23.6%) and signs of increased intracranial pressure (11.7%, 95%CI: 6.0%–18.9%). All other manifestations occurred in less than 10% of symptomatic NCC patients. Only four studies reported on the mortality rate of NCC. Conclusions NCC is a pleomorphic disease linked to a range of manifestations. Although definitions of manifestations were very rarely provided, and varied from study to study, the proportion of NCC cases with seizures/epilepsy and the proportion of headaches were consistent across studies. These estimates are only applicable to patients who are ill enough to seek care in neurology clinics and likely over estimate the frequency of manifestations among all NCC cases. PMID:21629722

Clinical manifestations associated with neurocysticercosis: a systematic review.

PubMed

Carabin, Hélène; Ndimubanzi, Patrick Cyaga; Budke, Christine M; Nguyen, Hai; Qian, Yingjun; Cowan, Linda Demetry; Stoner, Julie Ann; Rainwater, Elizabeth; Dickey, Mary

2011-05-01

The clinical manifestations of neurocysticercosis (NCC) are poorly understood. This systematic review aims to estimate the frequencies of different manifestations, complications and disabilities associated with NCC. A systematic search of the literature published from January 1, 1990, to June 1, 2008, in 24 different electronic databases and 8 languages was conducted. Meta-analyses were conducted when appropriate. A total of 1569 documents were identified, and 21 included in the analysis. Among patients seen in neurology clinics, seizures/epilepsy were the most common manifestations (78.8%, 95%CI: 65.1%-89.7%) followed by headaches (37.9%, 95%CI: 23.3%-53.7%), focal deficits (16.0%, 95%CI: 9.7%-23.6%) and signs of increased intracranial pressure (11.7%, 95%CI: 6.0%-18.9%). All other manifestations occurred in less than 10% of symptomatic NCC patients. Only four studies reported on the mortality rate of NCC. NCC is a pleomorphic disease linked to a range of manifestations. Although definitions of manifestations were very rarely provided, and varied from study to study, the proportion of NCC cases with seizures/epilepsy and the proportion of headaches were consistent across studies. These estimates are only applicable to patients who are ill enough to seek care in neurology clinics and likely over estimate the frequency of manifestations among all NCC cases.

Articular manifestations in patients with Lyme disease.

PubMed

Vázquez-López, María Esther; Díez-Morrondo, Carolina; Sánchez-Andrade, Amalia; Pego-Reigosa, Robustiano; Díaz, Pablo; Castro-Gago, Manuel

To determine the percentage of Lyme patients with articular manifestations in NW Spain and to know their evolution and response to treatment. A retrospective study (2006-2013) was performed using medical histories of confirmed cases of Lyme disease showing articular manifestations. Clinical and laboratory characteristics, together with the treatment and evolution of the patients, were analysed. Seventeen out of 108 LD confirmed patients (15.7%) showed articular manifestations. Regarding those 17 patients, 64.7%, 29.4% and 5.9% presented arthritis, arthralgia and bursitis, respectively. The knee was the most affected joint. Articular manifestations were often associated to neurological, dermatological and cardiac pathologies. Otherwise, most patients were in Stage III. The 11.8% of the cases progressed to a recurrent chronic arthritis despite the administration of an appropriate treatment. Lyme disease patients showing articular manifestations should be included in the diagnosis of articular affections in areas of high risk of hard tick bite, in order to establish a suitable and early treatment and to avoid sequels. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

19 CFR 18.13 - Procedure; manifest.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Procedure; manifest. 18.13 Section 18.13 Customs... TRANSPORTATION IN BOND AND MERCHANDISE IN TRANSIT Shipment of Baggage in Bond § 18.13 Procedure; manifest. (a...-121, 35 FR 8222, May 26, 1970; T.D. 77-241, 42 FR 54937, Oct. 12, 1977; T.D. 87-75, 52 FR 20067, May...

19 CFR 18.13 - Procedure; manifest.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Procedure; manifest. 18.13 Section 18.13 Customs... TRANSPORTATION IN BOND AND MERCHANDISE IN TRANSIT Shipment of Baggage in Bond § 18.13 Procedure; manifest. (a...-121, 35 FR 8222, May 26, 1970; T.D. 77-241, 42 FR 54937, Oct. 12, 1977; T.D. 87-75, 52 FR 20067, May...

19 CFR 18.13 - Procedure; manifest.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Procedure; manifest. 18.13 Section 18.13 Customs... TRANSPORTATION IN BOND AND MERCHANDISE IN TRANSIT Shipment of Baggage in Bond § 18.13 Procedure; manifest. (a...-121, 35 FR 8222, May 26, 1970; T.D. 77-241, 42 FR 54937, Oct. 12, 1977; T.D. 87-75, 52 FR 20067, May...

19 CFR 18.13 - Procedure; manifest.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Procedure; manifest. 18.13 Section 18.13 Customs... TRANSPORTATION IN BOND AND MERCHANDISE IN TRANSIT Shipment of Baggage in Bond § 18.13 Procedure; manifest. (a...-121, 35 FR 8222, May 26, 1970; T.D. 77-241, 42 FR 54937, Oct. 12, 1977; T.D. 87-75, 52 FR 20067, May...

19 CFR 18.13 - Procedure; manifest.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Procedure; manifest. 18.13 Section 18.13 Customs... TRANSPORTATION IN BOND AND MERCHANDISE IN TRANSIT Shipment of Baggage in Bond § 18.13 Procedure; manifest. (a...-121, 35 FR 8222, May 26, 1970; T.D. 77-241, 42 FR 54937, Oct. 12, 1977; T.D. 87-75, 52 FR 20067, May...

[Pulmonary manifestations in systemic lupus erythematosus].

PubMed

Vincze, Krisztina; Odler, Balázs; Müller, Veronika

2016-07-01

Systemic lupus erythematosus is the most common connective tissue disease that is associated with pulmonary manifestations. Although lupus has the potential to affect any organ, lung involvement is observed during the course of the disease in most cases and it is prognostic for outcome. Pulmonary manifestations in lupus can be classified into five groups based on the anatomical involvement: pleura, lung parenchyma, bronchi and bronchioli, lung vasculature and respiratory muscles can be involved. The most common respiratory manifestations attributable to lupus are pleuritis with or without pleural effusion, pulmonary vascular disease, upper and lower airway dysfunction, parenchymal disease, and diaphragmatic dysfunction (shrinking lung syndrome). In this article the authors summarize lung involvement of lupus, its diagnosis, therapy and prognosis. Orv. Hetil., 2016, 157(29), 1154-1160.

Gastrointestinal Manifestations in X-linked Agammaglobulinemia

PubMed Central

Barmettler, Sara; Otani, Iris M.; Minhas, Jasmit; Abraham, Roshini S.; Chang, Yenhui; Dorsey, Morna J.; Ballas, Zuhair K.; Bonilla, Francisco A.; Ochs, Hans D.; Walter, Jolan E.

2017-01-01

Purpose X-linked agammaglobulinemia is a primary humoral immunodeficiency characterized by hypogammaglobulinemia and increased susceptibility to infection. Although there is increased awareness of autoimmune and inflammatory complications in XLA, the spectrum of gastrointestinal manifestations has not previously been fully explored. Methods We present a case report of a family with two affected patients with XLA. Given the gastrointestinal involvement of the grandfather in this family, we performed a retrospective descriptive analysis of XLA patients with reported diagnoses of GI manifestations and inflammatory bowel disease (IBD) or enteritis registered at the USIDNet, a national registry of primary immunodeficiencies. Results In this cohort of patients with XLA, we found that up to 35% had concurrent gastrointestinal manifestations, and 10% had reported diagnoses of IBD or enteritis. The most commonly reported mutations were missense, which have been associated with a less severe XLA phenotype in the literature. The severity of symptoms were wide-ranging, and management strategies were diverse and mainly experimental. Conclusions Patients with XLA may require close monitoring with particular attention for GI manifestations including IBD and infectious enteritis. Further studies are needed to improve diagnosis and management of GI conditions in XLA patients. PMID:28236219

Media and Technology in Preschool Classrooms: Manifesting Prosocial Sharing Behaviours When Using iPads

ERIC Educational Resources Information Center

Ralph, Rachel

2018-01-01

This empirical case study investigated prosocial sharing behaviours when using media and technology, i.e., iPads. The following research questions were explored: (1) How do prosocial behaviours of sharing manifest among preschool-aged children interacting with iPads? (2) What are the effects of iPad use on the manifestation of prosocial sharing…

Effects of manifest ethnic identification on employment discrimination.

PubMed

Barron, Laura G; Hebl, Michelle; King, Eden B

2011-01-01

Evidence from recent laboratory experiments suggests that ethnic identification can lead to negative evaluations of ethnic minorities (Kaiser & Pratt-Hyatt, 2009). The current research considers the generalizability of these findings to face-to-face interactions in contexts wherein impression management concerns are salient: the workplace hiring process. In a field experiment, Black, Hispanic, and Irish individuals applied for retail jobs with or without visible display of their ethnic identification. Analysis of indicators of formal (e.g., application offering, interview scheduling) and interpersonal discrimination (e.g., interaction length, nonverbal negativity) suggest store personnel interacting with other-race applicants exhibited greater positivity and longer interactions when applicants displayed ethnic identification than when they did not. The findings suggest that psychologists need to understand not only attitudes or intentions expressed in the lab, but also the behavioral consequences of manifest group identity as they unfold in natural environments.

[Cardiovascular manifestations of human toxocariasis].

PubMed

Bolívar-Mejía, Adrián; Rodríguez-Morales, Alfonso J; Paniz-Mondolfi, Alberto E; Delgado, Olinda

2013-01-01

Toxocariasis is a parasitic infection produced by helminths that cannot reach their adult stage in humans. For their etiological species (Toxocara canis and Toxocara cati), man is a paratenic host. Infection by such helminths can produce a variety of clinical manifestations, such as: visceral larvae migrans syndrome, ocular larvae migrans syndrome and covert toxocariasis. In the visceral larvae migrans syndrome, the organs that are mainly involved include liver, lungs, skin, nervous system, muscles, kidneys and the heart. Regarding the latter, the importance of cardiovascular manifestations in toxocariasis, as well as its clinical relevance, has increasingly begun to be recognized. The current article is based on a systematic information search, focused mainly on the clinical and pathological aspects of cardiovascular manifestations in toxocariasis, including its pathophysiology, laboratory findings, diagnosis and therapeutical options, with the objective of highlighting its importance as a zoonosis and its relevance to the fields of cardiovascular medicine in adults and children. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

[Neuropsychiatric manifestations ushering pernicious anemia].

PubMed

Mrabet, S; Ellouze, F; Ellini, S; Mrad, M F

2015-12-01

Biermer disease or pernicious anemia is an autoimmune atrophic gastritis characterized by the lack of secretion of gastric intrinsic factor. This leads to an insufficient absorption of vitamin B12 in the ileum. Clinical manifestations are mainly hematologic. Neuropsychiatric manifestations are known but are less frequent especially early in the disease. Inaugural neuropsychiatric arrays are rare and various thus making diagnosis difficult. In this article, we report through two clinical cases different neuropsychiatric manifestations revealing pernicious anemia. Mrs. C.O., aged 56, presented after surgery for gallstones, an acute psychiatric array associated with gait disorders. She had no history of neurological or psychiatric problems. The psychiatric interview revealed delirious syndrome, depressive symptoms and anxiety. Neurological examination noted a flaccid paraplegia with peripheral neuropathic syndrome and myoclonus in the upper limbs. At the full blood count, a macrocytosis (VGM: 112.2fl) without anemia was found. The level of vitamin B12 in the blood was low. Cerebro-spinal MRI was suggestive of a neuro-Biermer and showed hyper signal in the cervical cord on T2-weighted sagittal section. In axial section, hyper signal appears at the posterior columns in the form of V. There were no brain abnormalities. A sensorimotor axonal polyneuropathy was diagnosed. The patient received vitamin B12 intramuscularly for ten days associated with neuroleptic treatment. Mrs. R.M., aged 40, was brought to the psychiatry consultation for acute behavioral disorders progressively worsening over a month. An anxiety syndrome, depressive syndrome and delirious syndrome were identified. Neurological examination showed a posterior cordonal syndrome with quadripyramidal syndrome. Full blood count showed a macrocytic anemia. Serum B12 level was collapsed. Cerebro-spinal MRI was normal. She received vitamin B12 with clinical and biological improvement. Features of pernicious anemia

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.

Otologic manifestations of Larsen syndrome.

PubMed

Marques, Letícia Helena de Sousa; Martins, Daniela Vieira; Juares, Gabriel Liria; Lorenzetti, Fábio Tadeu Moura; Monsanto, Rafael da Costa

2017-10-01

To describe and discuss otologic manifestations of Larsen syndrome, based on a case report and a systematic review of the literature. We performed a PubMED database search, and we selected studies reporting otolaryngologic manifestations secondary to Larsen syndrome. The selected articles were read in full, and three researchers independently extracted data from the studies. In parallel, we report the case of a 14-year-old patient who had hearing loss secondary to Larsen syndrome. Fifteen studies met our selection criteria. Seven studies reported hearing loss in patients with Larsen syndrome (4 had conductive hearing loss and 3 had mixed hearing loss). The conductive hearing loss may be secondary to ossicular malformations and/or middle ear effusions. Other causes for conductive hearing loss are mesenchymal remnants in the middle ear, Eustachian tube dysfunction, and cleft palate. Surgical management of the hearing loss is possible in selected cases, although the surgical and anesthetic risks should be considered. Hearing aids seem to be safe and effective treatment options for the hearing loss secondary to Larsen syndrome. Although rare, patients with Larsen syndrome may have hearing loss. The most frequent type of deficit is conductive, either secondary to malformation of the ossicles or middle ear effusion. Possible surgical correction of these abnormalities should be weighed against the anesthetic risks of these patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Breast manifestations of systemic diseases

PubMed Central

Dilaveri, Christina A; Mac Bride, Maire Brid; Sandhu, Nicole P; Neal, Lonzetta; Ghosh, Karthik; Wahner-Roedler, Dietlind L

2012-01-01

Although much emphasis has been placed on the primary presentations of breast cancer, little focus has been placed on how systemic illnesses may affect the breast. In this article, we discuss systemic illnesses that can manifest in the breast. We summarize the clinical features, imaging, histopathology, and treatment recommendations for endocrine, vascular, systemic inflammatory, infectious, and hematologic diseases, as well as for the extramammary malignancies that can present in the breast. Despite the rarity of these manifestations of systemic disease, knowledge of these conditions is critical to the appropriate evaluation and treatment of patients presenting with breast symptoms. PMID:22371658

Oral Manifestations in Pediatric Patients with Coeliac Disease – A Review Article

PubMed Central

Macho, Viviana Marisa Pereira; Coelho, Ana Sofia; Veloso e Silva, Diana Maria; de Andrade, David José Casimiro

2017-01-01

Background: Coeliac disease is a chronic enteropathy that remains a challenge for the clinician, due to its atypical manifestations and etiopathogenic complexity. Objective: This article intends to describe the oral characteristics of Coeliac Disease in children in order to facilitate their management in the dental office. Methods: A review of the literature was performed electronically in PubMed (PubMed Central, and MEDLINE) for articles published in English from 2000 to April of 2017. The article is also based on the authors' clinical experience with children with coeliac disease. The searched keywords were “coeliac disease “,”oral manifestations “, “dental enamel defects”, “recurrent aphthous stomatitis” and “oral aphthous ulcers”. Results: There are some oral manifestations which are strictly related to coeliac disease: dental enamel defects, recurrent aphthous stomatitis, delayed tooth eruption, multiple caries, angular cheilitis, atrophic glossitis, dry mouth and burning tongue. Conclusion: The complete knowledge of the oral manifestations of coeliac disease can trigger an effective change in the quality of life of the patients with this disease. PMID:29238414

Effective treatment by glycolic acid peeling for cutaneous manifestation of familial generalized acanthosis nigricans caused by FGFR3 mutation.

PubMed

Ichiyama, S; Funasaka, Y; Otsuka, Y; Takayama, R; Kawana, S; Saeki, H; Kubo, A

2016-03-01

Acanthosis nigricans (AN) can occur as a cutaneous manifestation of genetic diseases, one of which is associated with activating mutations of the fibroblast growth factor receptor 3 gene (FGFR3). We explored familial AN patients with FGFR3 mutations and examined the effectiveness of glycolic acid (GA) peeling in improving their skin manifestations. Sanger sequencing was performed for the genomic DNA extracted from leucocytes of the family members involving familial AN. GA peeling was carried out for the two patients of familial AN once every 2 weeks. Heterozygous c.1949A>C (p.K650T) mutation in FGFR3 was identified for the affected family members examined, whereas the wild-type sequence was found for two unaffected individuals. Hyperpigmentation and coarseness of the skin were improved by GA peeling at regular intervals with few adverse effects. We diagnosed our cases as familial generalized AN caused by heterozygous c.1949A>C (p.K650T) mutation of FGFR3. We propose that GA peeling is a useful and safe therapeutic option to treat familial AN. © 2016 European Academy of Dermatology and Venereology.

Beyond the CRAB symptoms: a study of presenting clinical manifestations of multiple myeloma.

PubMed

Talamo, Giampaolo; Farooq, Umar; Zangari, Maurizio; Liao, Jason; Dolloff, Nathan G; Loughran, Thomas P; Epner, Elliot

2010-12-01

Although the typical clinical manifestations of multiple myeloma (MM) are summarized by the CRAB symptoms (hypercalcemia, renal insufficiency, anemia, and bone lesions), a significant proportion of patients with MM present with a variety of other clinical manifestations. We conducted a study evaluating the presenting symptoms that led to the diagnosis of MM. We conducted a retrospective review of 170 consecutive patients with MM seen at the Penn State Hershey Cancer Institute. Among patients with symptomatic MM, 74% presented with CRAB symptoms, 20% presented with non-CRAB manifestations, and 6% had both clinical features. Ten categories of non-CRAB manifestations were found, in order of decreasing frequency: neuropathy (because of spinal cord compression, nerve root compression, or peripheral neuropathy), extramedullary involvement, hyperviscosity syndrome, concomitant amyloidosis (eg, nephrotic syndrome or cardiopathy), hemorrhage/coagulopathy, systemic symptoms (eg, fever or weight loss), primary plasma cell leukemia, infections, cryoglobulinemia, and secondary gout. Kaplan-Meier estimates of survival in patients with non-CRAB manifestations did not show a significant difference from the survival of patients presenting with CRAB symptoms. Presenting symptoms of MM may be grouped in a total of 14 categories, 4 for the CRAB and 10 for the less common non-CRAB features. Grouped together, non-CRAB manifestations do not appear to confer a negative effect on the prognosis of patients with MM.

40 CFR 263.20 - The manifest system.

Code of Federal Regulations, 2014 CFR

2014-07-01

... accompany a hazardous waste shipment is satisfied when a copy of an electronic manifest is accessible during... CFR 177.817, a hazardous waste transporter must carry one printed copy of the electronic manifest on... unavailable for any reason, then: (i) The transporter in possession of the hazardous waste when the electronic...

19 CFR 123.22 - In-transit manifest.

Code of Federal Regulations, 2011 CFR

2011-04-01

... separate in-transit manifest is not required. (b) Additional copies. In the following cases additional... train sheet shall also be presented. (4) In all other cases where no in-transit manifest form is... enter and reenter Canada in a continuing movement en route to a final destination in the United States...

19 CFR 123.22 - In-transit manifest.

Code of Federal Regulations, 2014 CFR

2014-04-01

... separate in-transit manifest is not required. (b) Additional copies. In the following cases additional... train sheet shall also be presented. (4) In all other cases where no in-transit manifest form is... enter and reenter Canada in a continuing movement en route to a final destination in the United States...

19 CFR 123.22 - In-transit manifest.

Code of Federal Regulations, 2013 CFR

2013-04-01

... separate in-transit manifest is not required. (b) Additional copies. In the following cases additional... train sheet shall also be presented. (4) In all other cases where no in-transit manifest form is... enter and reenter Canada in a continuing movement en route to a final destination in the United States...

Antioxidant effect of Arabic gum against mercuric chloride-induced nephrotoxicity.

PubMed

Gado, Ali M; Aldahmash, Badr A

2013-01-01

The effects of Arabic gum (AG) against nephrotoxicity of mercury (Hg), an oxidative-stress inducing substance, in rats were investigated. A single dose of mercuric chloride (5 mg/kg intraperitoneal injection) induced renal toxicity, manifested biochemically by a significant increase in serum creatinine, blood urea nitrogen, thiobarbituric acid reactive substances, and total nitrate/nitrite production in kidney tissues. In addition, reduced glutathione, glutathione peroxidase, and catalase enzymes in renal tissues were significantly decreased. Pretreatment of rats with AG (7.5 g/kg/day per oral administration), starting 5 days before mercuric chloride injection and continuing through the experimental period, resulted in a complete reversal of Hg-induced increase in creatinine, blood urea nitrogen, thiobarbituric acid reactive substances, and total nitrate/nitrite to control values. Histopathologic examination of kidney tissues confirmed the biochemical data; pretreatment of AG prevented Hg-induced degenerative changes of kidney tissues. These results indicate that AG is an efficient cytoprotective agent against Hg-induced nephrotoxicity by a mechanism related at least in part to its ability to decrease oxidative and nitrosative stress and preserve the activity of antioxidant enzymes in kidney tissues.

Endocrine manifestations and management of Prader-Willi syndrome.

PubMed

Emerick, Jill E; Vogt, Karen S

2013-08-21

Prader-Willi syndrome (PWS) is a complex genetic disorder, caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13. In infancy it is characterized by hypotonia with poor suck resulting in failure to thrive. As the child ages, other manifestations such as developmental delay, cognitive disability, and behavior problems become evident. Hypothalamic dysfunction has been implicated in many manifestations of this syndrome including hyperphagia, temperature instability, high pain threshold, sleep disordered breathing, and multiple endocrine abnormalities. These include growth hormone deficiency, central adrenal insufficiency, hypogonadism, hypothyroidism, and complications of obesity such as type 2 diabetes mellitus. This review summarizes the recent literature investigating optimal screening and treatment of endocrine abnormalities associated with PWS, and provides an update on nutrition and food-related behavioral intervention. The standard of care regarding growth hormone therapy and surveillance for potential side effects, the potential for central adrenal insufficiency, evaluation for and treatment of hypogonadism in males and females, and the prevalence and screening recommendations for hypothyroidism and diabetes are covered in detail. PWS is a genetic syndrome in which early diagnosis and careful attention to detail regarding all the potential endocrine and behavioral manifestations can lead to a significant improvement in health and developmental outcomes. Thus, the important role of the provider caring for the child with PWS cannot be overstated.

Mitochondrial biotransformation of ω-(phenoxy)alkanoic acids, 3-(phenoxy)acrylic acids, and ω-(1-methyl-1H-imidazol-2-ylthio)alkanoic acids: A prodrug strategy for targeting cytoprotective antioxidants to mitochondria

PubMed Central

Roser, Kurt S.; Brookes, Paul S.; Wojtovich, Andrew P.; Olson, Leif P.; Shojaie, Jalil; Parton, Richard L.; Anders, M. W.

2010-01-01

Mitochondrial reactive oxygen species (ROS) generation and the attendant mitochondrial dysfunction are implicated in a range of disease states. The objective of the present studies was to test the hypothesis that the mitochondrial β-oxidation pathway could be exploited to deliver and biotransform the prodrugs ω-(phenoxy)alkanoic acids, 3-(phenoxy)acrylic acids, and ω-(1-methyl-1H-imidazol-2-ylthio)alkanoic acids to the corresponding phenolic antioxidants or methimazole. 3 -and 5-(Phenoxy)alkanoic acids and methyl-substituted analogs were biotransformed to phenols; rates of biotransformation decreased markedly with methyl-group substitution on the phenoxy moiety. 2,6-Dimethylphenol formation from the analogs 3-([2,6-dimethylphenoxy]methylthio)propanoic acid and 3-(2,6-dimethylphenoxy)acrylic acid was greater than that observed with ω-(2,6-dimethylphenoxy)alkanoic acids. 3- and 5-(1-Methyl-1H-imidazol-2-ylthio)alkanoic acids were rapidly biotransformed to the antioxidant methimazole and conferred significant cytoprotection against hypoxia-reoxygenation injury in isolated cardiomyocytes. Both 3-(2,6-dimethylphenoxy)propanoic acid and 3-(2,6-dimethylphenoxy)acrylic acid also afforded cytoprotection against hypoxia-reoxygenation injury in isolated cardiomyocytes. These results demonstrate that mitochondrial β-oxidation is a potentially useful delivery system for targeting antioxidants to mitochondria. PMID:20129794

Manifestations of Indirect Self-Destructiveness and Dimensions of Emotional Intelligence.

PubMed

Tsirigotis, Konstantinos; Łuczak, Joanna

2016-09-01

While indirect self-destructiveness exerts a rather negative influence on the life and psychological and social functioning of the individual, emotional intelligence may have a favourable effect. The aim of this study has been to explore possible relationships between manifestations of indirect self-destructiveness and dimensions of emotional intelligence. A population of 260 individuals (130 females and 130 males) aged 20-30 (mean age of 24.5) was studied by using the Polish version of the Chronic Self-Destructiveness Scale and INTE, i.e., the Polish version of the Assessing Emotions Scale. Manifestations of indirect self-destructiveness show many significant correlations with variables of the INTE, and those correlations are negative. Generally, it can be said that low emotional intelligence is associated with poor psychosocial and social functioning, which, in turn, is associated with indirect self-destructiveness and its manifestations. It seems advisable to use emotional intelligence in the prophylactic and therapeutic work with individuals suffering from various types of disorders, especially the syndrome of indirect self-destructiveness.

e-Manifest for Hazardous Wastes in New Mexico

EPA Pesticide Factsheets

EPA launches the hazardous waste electronic manifest (e-Manifest) system on June 30, 2018. The fact sheets here are written from EPA's federal perspective but do contain useful information about New Mexico

Neuropsychiatric manifestations and their outcomes in chronic hypocalcaemia.

PubMed

Maiti, Abhishek; Chatterjee, Sudip

2013-03-01

Hypocalcaemia is an established cause of neurological and psychiatric disease with numerous clinical manifestations. The aim of the study was to determine the outcome of severe neuropsychiatric manifestations of chronic hypocalcaemia after correction of calcium levels. Clinical and laboratory data of 22 patients seen between 1999 and 2009 were retrospectively analysed. Calcium, magnesium, phosphorus, albumin and parathormone values were measured in all cases. All patients except infants under one year of age had computed tomography (CT) scans of the head. Most patients (n = 19; 86%) presented with generalised tonic clonic convulsions while three had seizures with psychiatric manifestations. Movement disorders were present in 4 patients and one had candida meningitis. Nineteen of the 22 patients had primary hypoparathyroidism of which one had associated mucocutaneous candidiasis. One had pseudohypoparathyroidism and two had vitamin D deficiency. All patients improved with calcitriol and calcium treatment. Twelve of the 14 patients with convulsions could be taken off anticonvulsants. Hemiballismus disappeared in one patient and choreiform movements disappeared in one patient and dystonia in two patients. Psychiatric manifestations improved but did not disappear in the three patients who had them. Adult patients with seizures or neuropsychiatric manifestations should have calcium levels checked. Seizure disorders due to chronic hypocalcaemia had excellent prognosis on correction of serum calcium levels. Movement disorders improved markedly. Psychiatric manifestations did not improve substantially on correction of serum calcium levels.

40 CFR 267.71 - Use of the manifest system.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Within 30 days after the delivery, send a copy of the manifest to the generator; and (5) Retain at the... numbers, generator's certification, and signatures), the owner or operator, or his agent, must: (1) Sign..., send a copy of the signed and dated manifest to the generator; however, if the manifest has not been...

Neurological manifestations of excessive alcohol consumption.

PubMed

Planas-Ballvé, Anna; Grau-López, Laia; Morillas, Rosa María; Planas, Ramón

2017-12-01

This article reviews the different acute and chronic neurological manifestations of excessive alcohol consumption that affect the central or peripheral nervous system. Several mechanisms can be implicated depending on the disorder, ranging from nutritional factors, alcohol-related toxicity, metabolic changes and immune-mediated mechanisms. Recognition and early treatment of these manifestations is essential given their association with high morbidity and significantly increased mortality. Copyright © 2017 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

Magmas functions as a ROS regulator and provides cytoprotection against oxidative stress-mediated damages

PubMed Central

Srivastava, S; Sinha, D; Saha, P P; Marthala, H; D'Silva, P

2014-01-01

Redox imbalance generates multiple cellular damages leading to oxidative stress-mediated pathological conditions such as neurodegenerative diseases and cancer progression. Therefore, maintenance of reactive oxygen species (ROS) homeostasis is most important that involves well-defined antioxidant machinery. In the present study, we have identified for the first time a component of mammalian protein translocation machinery Magmas to perform a critical ROS regulatory function. Magmas overexpression has been reported in highly metabolically active tissues and cancer cells that are prone to oxidative damage. We found that Magmas regulates cellular ROS levels by controlling its production as well as scavenging. Magmas promotes cellular tolerance toward oxidative stress by enhancing antioxidant enzyme activity, thus preventing induction of apoptosis and damage to cellular components. Magmas enhances the activity of electron transport chain (ETC) complexes, causing reduced ROS production. Our results suggest that J-like domain of Magmas is essential for maintenance of redox balance. The function of Magmas as a ROS sensor was found to be independent of its role in protein import. The unique ROS modulatory role of Magmas is highlighted by its ability to increase cell tolerance to oxidative stress even in yeast model organism. The cytoprotective capability of Magmas against oxidative damage makes it an important candidate for future investigation in therapeutics of oxidative stress-related diseases. PMID:25165880

49 CFR 176.30 - Dangerous cargo manifest.

Code of Federal Regulations, 2010 CFR

2010-10-01

... purpose by the carrier or agents shall prepare a dangerous cargo manifest, list, or stowage plan. This... number as prescribed in subpart G of part 172 of this subchapter. (4) The number and description of... paragraphs (a)(3) and (a)(5) of this section. The person who supervises the preparation of the manifest, list...

How to Participate: Testing the Hazardous Waste Electronic Manifest System System (e-Manifest)

EPA Pesticide Factsheets

This page explains options for stakeholders like TSDFs and generators who wish to contribute to the discussion about the development of e-manifest. Directions are provided here to help the stakeholders test and provide feedback on the system.

Leukemic Oral Manifestations and their Management.

PubMed

Francisconi, Carolina Favaro; Caldas, Rogerio Jardim; Oliveira Martins, Lazara Joyce; Fischer Rubira, Cassia Maria; da Silva Santos, Paulo Sergio

2016-01-01

Leukemia is the most common neoplastic disease of the white blood cells which is important as a pediatric malignancy. Oral manifestations occur frequently in leukemic patients and may present as initial evidence of the disease or its relapse. The symptoms include gingival enlargement and bleeding, oral ulceration, petechia, mucosal pallor, noma, trismus and oral infections. Oral lesions arise in both acute and chronic forms of all types of leukemia. These oral manifestations either may be the result of direct infiltration of leukemic cells (primary) or secondary to underlying thrombocytopenia, neutropenia, or impaired granulocyte function. Despite the fact that leukemia has long been known to be associated with oral lesions, the available literature on this topic consists mostly of case reports, without data summarizing the main oral changes for each type of leukemia. Therefore, the present review aimed at describing oral manifestations of all leukemia types and their dental management. This might be useful in early diagnosis, improving patient outcomes.

Cutaneous Manifestations of Systemic Lupus Erythematosus

PubMed Central

Uva, Luís; Miguel, Diana; Pinheiro, Catarina; Freitas, João Pedro; Marques Gomes, Manuel; Filipe, Paulo

2012-01-01

Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease of unknown etiology with many clinical manifestations. The skin is one of the target organs most variably affected by the disease. The American College of Rheumatology (ACR) established 11 criteria as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individuals and do not do well in that capacity. Cutaneous lesions account for four of these 11 revised criteria of SLE. Skin lesions in patients with lupus may be specific or nonspecific. This paper covers the SLE-specific cutaneous changes: malar rash, discoid rash, photosensitivity, and oral mucosal lesions as well as SLE nonspecific skin manifestations, their pathophysiology, and management. A deeper thorough understanding of the cutaneous manifestations of SLE is essential for diagnosis, prognosis, and efficient management. Thus, dermatologists should cooperate with other specialties to provide optimal care of SLE patient. PMID:22888407

Hazardous Waste Manifest System

EPA Pesticide Factsheets

EPA’s hazardous waste manifest system is designed to track hazardous waste from the time it leaves the generator facility where it was produced, until it reaches the off-site waste management facility that will store, treat, or dispose of the waste.

Cytoprotective role of autophagy against BH3 mimetic gossypol in ATG5 knockout cells generated by CRISPR-Cas9 endonuclease.

PubMed

Kim, Na-Yeon; Han, Byeal-I; Lee, Michael

2016-01-01

Previously, we demonstrated the association between autophagy and gossypol-induced growth inhibition of mutant BRAF melanoma cells. Here, we investigate the role of autophagy in ATG5 knockout cell lines generated by the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas-mediated genome editing. The MTT assay revealed that the inhibitory effect of gossypol was weaker on ATG5 knockout cells than that on the wild type (WT) cells. The conversion of non-autophagic LC3-I to autophagic LC3-II and RT-PCR confirmed the functional gene knockout. However, Cyto-ID autophagy assay revealed that gossypol induced ATG5- and LC3-independent autophagy in ATG5 knockout cells. Moreover, gossypol acts as an autophagy inducer in ATG5 knockout cells while blocking the later stages of the autophagy process in WT cells, which was determined by measuring autophagic flux after co-treatment of gossypol with chloroquine (late-stage autophagy inhibitor). On the other hand, inhibition of autophagy with 3-MA or Beclin-1 siRNA caused a partial increase in the sensitivity to gossypol in ATG5 knockout cells, but not in the WT cells. Together, our findings suggest that the resistance to gossypol in ATG5 knockout cells is associated with increased cytoprotective autophagy, independent of ATG5. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Frequent Questions about the Hazardous Waste Manifest Form

EPA Pesticide Factsheets

FAQs including Are generators required to use all six copies of the manifest? How will state-only waste manifests be affected by the new rule? Where must the importer and foreign generator’s information be entered in the generator identification block?

[Streptococcus suis infection--clinical manifestations].

PubMed

Dragojlović, Julijana; Milosević, Branko; Sasić, Neda; Pelemis, Mijomir; Sasić, Milan

2005-01-01

Streptococcus suis is a bacterium causing a disease in pigs and rarely in humans. This zoonosis is mostly found as a sporadic disease in individuals that were in contact with the affected or infected pigs: farmers, veterinarians and workers engaged in fresh pork processing. It is assumed that the bacterium enters the body through a cut abrasion in the skin. Initially, the condition resembles a flu, followed by signs of bacteriemia and sepsis. The most frequent clinical manifestation of Streptococcus suis infection is meningitis, leading to hearing loss in over 75% of patients, and subsequent arthritis, endophtalmitis, endocarditis and pneumonia. Toxic shock syndrome with hemorhagic manifestations rarely develops. This study included five male patients aged 22 to 63 years treated in the Intensive Care Unit of the Institute of Infectious and Tropical Diseases in Belgrade, due to Streptococcus suis infection. The aim of this study was to point to the existence of this bacteria in our environment, to describe clinical manifestations of the disease and to point out the importance of its prevention. All patients had epidemiological evidence of being in contact with pork meat. There were no data about diseased pigs. The estimated incubation period was 4 to 8 days. All patients had meningeal signs. Clinical symptoms included shivering, fever, vomiting, headache, malaise, vertigo and tinitus. Three patients presented with alerterd level of awarrness. Four patients developed very severe bilateral hearing impairment, whereas one endophtalmtis and one developed endocarditis. The cerebrospinal fluid (CSF) was opalescent in four patients, and only one patient presented with clear CSF. CSF examination showed typical changes characteristic for bacterial meningitis. Streptoccocus suis was isolated in CSF in all patients, and in one patient the bacteria was isolated in blood as well. All patients underwent treatement with II and III generation cephalosporins and one with one

Detection of disease outbreaks by the use of oral manifestations.

PubMed

Torres-Urquidy, M H; Wallstrom, G; Schleyer, T K L

2009-01-01

Oral manifestations of diseases caused by bioterrorist agents could be a potential data source for biosurveillance. This study had the objectives of determining the oral manifestations of diseases caused by bioterrorist agents, measuring the prevalence of these manifestations in emergency department reports, and constructing and evaluating a detection algorithm based on them. We developed a software application to detect oral manifestations in free text and identified positive reports over three years of data. The normal frequency in reports for oral manifestations related to anthrax (including buccal ulcers-sore throat) was 7.46%. The frequency for tularemia was 6.91%. For botulism and smallpox, the frequencies were 0.55% and 0.23%. We simulated outbreaks for these bioterrorism diseases and evaluated the performance of our system. The detection algorithm performed better for smallpox and botulism than for anthrax and tularemia. We found that oral manifestations can be a valuable tool for biosurveillance.

BAG3 Overexpression and Cytoprotective Autophagy Mediate Apoptosis Resistance in Chemoresistant Breast Cancer Cells.

PubMed

Das, Chandan Kanta; Linder, Benedikt; Bonn, Florian; Rothweiler, Florian; Dikic, Ivan; Michaelis, Martin; Cinatl, Jindrich; Mandal, Mahitosh; Kögel, Donat

2018-03-01

Target-specific treatment modalities are currently not available for triple-negative breast cancer (TNBC), and acquired chemotherapy resistance is a primary obstacle for the treatment of these tumors. Here we employed derivatives of BT-549 and MDA-MB-468 TNBC cell lines that were adapted to grow in the presence of either 5-Fluorouracil, Doxorubicin or Docetaxel in an aim to identify molecular pathways involved in the adaptation to drug-induced cell killing. All six drug-adapted BT-549 and MDA-MB-468 cell lines displayed cross resistance to chemotherapy and decreased apoptosis sensitivity. Expression of the anti-apoptotic co-chaperone BAG3 was notably enhanced in two thirds (4/6) of the six resistant lines simultaneously with higher expression of HSP70 in comparison to parental controls. Doxorubicin-resistant BT-549 (BT-549 r DOX 20 ) and 5-Fluorouracil-resistant MDA-MB-468 (MDA-MB-468 r 5-FU 2000 ) cells were chosen for further analysis with the autophagy inhibitor Bafilomycin A1 and lentiviral depletion of ATG5, indicating that enhanced cytoprotective autophagy partially contributes to increased drug resistance and cell survival. Stable lentiviral BAG3 depletion was associated with a robust down-regulation of Mcl-1, Bcl-2 and Bcl-xL, restoration of drug-induced apoptosis and reduced cell adhesion in these cells, and these death-sensitizing effects could be mimicked with the BAG3/Hsp70 interaction inhibitor YM-1 and by KRIBB11, a selective transcriptional inhibitor of HSF-1. Furthermore, BAG3 depletion was able to revert the EMT-like transcriptional changes observed in BT-549 r DOX 20 and MDA-MB-468 r 5-FU 2000 cells. In summary, genetic and pharmacological interference with BAG3 is capable to resensitize TNBC cells to treatment, underscoring its relevance for cell death resistance and as a target to overcome therapy resistance of breast cancer. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Clinical Profile of Atypical Manifestations of Dengue Fever.

PubMed

Pothapregada, Sriram; Kamalakannan, Banupriya; Thulasingam, Mahalakshmy

2016-06-01

To study the clinical profile and outcome of the atypical manifestations of dengue fever in children. All children (0-12 y of age) diagnosed and confirmed as dengue fever at a tertiary care hospital at Puducherry, between the 1st of August 2012 and January 31st 2015 were reviewed retrospectively from hospital case records as per the revised World Health Organization (WHO) guidelines 2011 for dengue fever. The diagnosis was confirmed by NS1 antigen-based ELISA test or dengue serology for IgM and IgG antibodies and the data was analyzed using SPSS 16.0 statistical software. Out of 254 children admitted with dengue fever, non-severe dengue and severe dengue were seen in 62.6 % and 37.4 % respectively. Atypical manifestations were seen in 106 cases (41.7 %). Mean age of presentation was 6.9(3.3) y. M: F ratio was 1.2:1. The common manifestations of severe dengue infection were shock (37.4 %), bleeding (20.1 %) and multi-organ dysfunction (2.4 %). The most common atypical manifestations of dengue fever were lymphadenopathy (41.7 %), splenomegaly (21.2 %), biphasic fever (18.1 %), hepatitis (11.4 %), febrile diarrhea (6.3 %), refractory shock (2.4 %) and impaired consciousness (1.9 %). The other atypical manifestations present were portal hypertension, acalculous cholecystitis, appendicitis, acute respiratory distress syndrome (ARDS), myocarditis, pericardial effusion, paroxysmal supraventricular tachycardia (PSVT), myositis, acute kidney injury (AKI), hemophagocytic syndrome and disseminated intravascular coagulopathy (DIC). Platelet count did not always correlate well with the severity of bleeding. There were six deaths (2.4 %) and out of them four presented with impaired consciousness (66.6 %). The common causes for poor outcome were multiorgan failure, encephalopathy and refractory shock. The atypical manifestations of dengue fever are no more a rare entity. Clinicians should have a high index of suspicion and vigilance for atypical manifestations of

The extrahepatic manifestations of hepatitis B virus.

PubMed

Baig, Saeeda; Alamgir, Mohiuddin

2008-07-01

Hepatitis B Virus (HBV) leads to a number of hepatic complications, from acute to chronic hepatitis, cirrhosis and hepatocellular carcinoma, is a well-established fact. Upcoming clinical research, over the years, associates numerous extrahepatic manifestations during the acute and chronic episodes of hepatitis B with significant morbidity and mortality. A causal relationship between HBV and serious autoimmune disorders has also been observed among certain susceptible vaccine recipients in a defined temporal period following immunization. The cause of these extrahepatic manifestations is generally believed to be immune mediated. The most commonly described include skin rash, arthritis, arthralgia, glomerulonephritis, polyarteritis nodosa, and papular acrodermatitis etc. The serum-sickness like "arthritis-dermatitis" prodrome has also been observed in approximately one-third of patients acquiring HBV infections. Skin manifestations of HBV infection typically present as palpable purpura reported to be caused by chronic HBV, although this association remains controversial. To consider the relationship between HBV and other clinically significant disorders as well as serious autoimmune disorders among certain vaccine recipients is the topic of this review. Variable factors that influence extrahepatic manifestation are discussed, including possible synergy between hepatitis B virus and the immune system.

Stroke as the Initial Manifestation of Atrial Fibrillation: The Framingham Heart Study.

PubMed

Lubitz, Steven A; Yin, Xiaoyan; McManus, David D; Weng, Lu-Chen; Aparicio, Hugo J; Walkey, Allan J; Rafael Romero, Jose; Kase, Carlos S; Ellinor, Patrick T; Wolf, Philip A; Seshadri, Sudha; Benjamin, Emelia J

2017-02-01

To prevent strokes that may occur as the first manifestation of atrial fibrillation (AF), screening programs have been proposed to identify patients with undiagnosed AF who may be eligible for treatment with anticoagulation. However, the frequency with which patients with AF present with stroke as the initial manifestation of the arrhythmia is unknown. We estimated the frequency with which AF may present as a stroke in 1809 community-based Framingham Heart Study participants with first-detected AF and without previous strokes, by tabulating the frequencies of strokes occurring on the same day, within 30 days before, 90 days before, and 365 days before first-detected AF. Using previously reported AF incidence rates, we estimated the incidence of strokes that may represent the initial manifestation of AF. We observed 87 strokes that occurred ≤1 year before AF detection, corresponding to 1.7% on the same day, 3.4% within 30 days before, 3.7% within 90 days before, and 4.8% ≤1 year before AF detection. We estimated that strokes may present as the initial manifestation of AF at a rate of 2 to 5 per 10 000 person-years, in both men and women. We observed that stroke is an uncommon but measureable presenting feature of AF. Our data imply that emphasizing cost-effectiveness of population-wide AF-screening efforts will be important given the relative infrequency with which stroke represents the initial manifestation of AF. © 2017 American Heart Association, Inc.

Urological Manifestations of Henoch-Schonlein Purpura: A Review

PubMed Central

Dalpiaz, Amanda; Schwamb, Richard; Miao, Yimei; Gonka, Jacquelyn; Walzter, Wayne; Khan, Sardar A.

2015-01-01

Henoch-Schonlein purpura (HSP) is an immune-mediated systemic vasculitis generally found in children. The standard manifestations of HSP are palpable purpura, arthritis, abdominal pain, and renal complications. Although less common, there are significant urological manifestations associated with HSP. The primary objective of this review is to encourage better understanding and management of HSP by emphasizing the common and rare manifestations of HSP, how they are diagnosed, and the latest treatment options for mild to severe complications. Medline searches of HSP and its urological manifestations were conducted along with searches on current diagnostic and treatment methods. Urological manifestations of HSP involve the kidney, ureter, bladder, prostate, scrotum, testicle, and penis. Diagnosis and management of HSP are not always clear due to differential diagnosis and diversity of symptom presentation. Treatment for HSP is mainly supportive and includes use of nonsteroidal anti-inflammatory drugs for pain relief. In more severe cases, glucocorticoids, methylprednisolone, plasmapheresis, and peritoneal and hemodialysis are reported successful. It is important to note different symptoms of HSP in order to distinguish HSP from other diseases. Early diagnosis may prevent severe complications. Treatment options vary from conservative to invasive depending on the severity of the disease and time frame of diagnosis. PMID:26889120

Holism and life manifestations: molecular and space-time biology.

PubMed

Krecek, J

2010-01-01

Appeals of philosophers to look for new concepts in sciences are being met with a weak response. Limited attention is paid to the relation between synthetic and analytic approach in solving problems of biology. An attempt is presented to open a discussion on a possible role of holism. The term "life manifestations" is used in accordance with phenomenology. Multicellular creatures maintain milieu intérieur to keep an aqueous milieu intracellulair in order to transform the energy of nutrients into the form utilizable for driving cellular life manifestations. Milieu intérieur enables to integrate this kind of manifestations into life manifestations of the whole multicellular creatures. The integration depends on a uniqueness and uniformity of the genome of cells, on their mutual recognition and adherence. The processes of ontogenetic development represent the natural mode of integration of cellular life manifestations. Functional systems of multicellular creatures are being established by organization of integrable cells using a wide range of developmental processes. Starting from the zygote division the new being displays all properties of a whole creature, although its life manifestations vary. Therefore, the whole organism is not only more than its parts, as supposed by holism, but also more than developmental stages of its life manifestations. Implicitly, the units of whole multicellular creature are rather molecular and developmental events than the cells per se. Holism, taking in mind the existence of molecular and space-time biology, could become a guide in looking for a new mode of the combination of analytical and synthetic reasoning in biology.

Pulmonary manifestations of rheumatologic diseases.

PubMed

Cidon, Michal; Bansal, Manvi; Hartl, Dominik

2017-06-01

The present review intends to provide an overview of the diversity and complexity of pulmonary manifestations of rheumatologic diseases and gaps in knowledge to effectively manage them. Diffuse lung disease in children with rheumatologic diseases represents a heterogeneous group of autoimmune disorders. Despite their significant morbidity and mortality, we have limited understanding about their pathogenesis. Here, we provide an overview of the pathophysiology and current management approach of these disorders, highlighting tools which assist with diagnosis, risk stratification and therapy. In this context, we address the need to develop a standardized approach to diagnose at-risk patients with rheumatologic disease and to predict their progression and the need to develop robust studies which evaluate the factors and interventions that influence pulmonary disease outcome. Diffuse lung disease in children with rheumatologic diseases represents a heterogeneous group of severe autoimmune disorders. By adopting a collaborative research approach among multicenters to help diagnose, risk stratify, and understand disease progression, effective management decisions can be optimized to improve clinical outcome.

40 CFR 264.71 - Use of manifest system.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Within 30 days of delivery, send a copy of the manifest to the generator; and (v) Retain at the facility..., NW., Washington, DC 20460. (b) If a facility receives, from a rail or water (bulk shipment... on the manifest (excluding the EPA identification numbers, generator's certification, and signatures...

Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK

PubMed Central

Panisello-Roselló, Arnau; Verde, Eva; Flores, Marta; Folch-Puy, Emma; Rolo, Anabela; Palmeira, Carlos; Hotter, Georgina; Adam, René; Roselló-Catafau, Joan

2018-01-01

Institute Goeorges Lopez 1 (IGL-1) and Histidine-Tryptophan-Ketoglutarate (HTK) preservation solutions are regularly used in clinical for liver transplantation besides University of Wisconsin (UW) solution and Celsior. Several clinical trials and experimental works have been carried out comparing all the solutions, however the comparative IGL-1 and HTK appraisals are poor; especially when they deal with the underlying protection mechanisms of the fatty liver graft during cold storage. Fatty livers from male obese Zücker rats were conserved for 24 h at 4 °C in IGL-1 or HTK preservation solutions. After organ recovery and rinsing of fatty liver grafts with Ringer Lactate solution, we measured the changes in mechanistic target of rapamycin (mTOR) signaling activation, liver autophagy markers (Beclin-1, Beclin-2, LC3B and ATG7) and apoptotic markers (caspase 3, caspase 9 and TUNEL). These determinations were correlated with the prevention of liver injury (aspartate and alanine aminostransferase (AST/ALT), histology) and mitochondrial damage (glutamate dehydrogenase (GLDH) and confocal microscopy findings). Liver grafts preserved in IGL-1 solution showed a marked reduction on p-TOR/mTOR ratio when compared to HTK. This was concomitant with significant increased cyto-protective autophagy and prevention of liver apoptosis, including inflammatory cytokines such as HMGB1. Together, our results revealed that IGL-1 preservation solution better protected fatty liver grafts against cold ischemia damage than HTK solution. IGL-1 protection was associated with a reduced liver damage, higher induced autophagy and decreased apoptosis. All these effects would contribute to limit the subsequent extension of reperfusion injury after graft revascularization in liver transplantation procedures. PMID:29364854

Dermatological manifestations in hemodialysis patients in Iran: A systematic review and meta-analysis.

PubMed

Asayesh, Hamid; Peykari, Niloofar; Pavaresh-Masoud, Mohammad; Esmaeili Abdar, Mohammad; Tajbakhsh, Ramin; Mousavi, Seyed Mojtaba; Djalalinia, Shirin; Noroozi, Mehdi; Qorbani, Mostafa; Mahdavi-Gorabi, Armita

2018-03-25

Dermatologic complications are common in patients with end-stage renal disease and also have a high diversity. This meta-analysis reviews prevalence of dermatological manifestations among hemodialysis patients in Iran. Using PubMed and NLM Gateway (for MEDLINE), Institute of Scientific Information (ISI), and SCOPUS as the main international electronic data sources, and Iran-Medex, Irandoc, and Scientific Information Database, as the main domestic databases with systematic search capability, we systematically searched surveys, papers, and reports on the prevalence of dermatological manifestations (until February 2016). Heterogeneity of reported prevalence's between studies was assessed using the Q test; overall prevalence of dermatological manifestations was estimated using random-effect meta-analysis model. We found 1229 records; from them, a total of eight studies comprising 917 hemodialysis patients were included. In all of studies, skin discoloration, pruritus and xerosis have the highest prevalence. According to random-effect meta-analysis model, the pooled prevalence of skin discoloration, pruritus, ecchymosis, xerosis, and half-and-half nail in hemodialysis patients were 48.03% (95% CI: 45.09-51.01), 52.85% (95%CI: 49.23-56.47), 19.88 (95% CI: 17.57-22.19), 51.14% (95% CI: 48.25-54.02), and 18.50% (95% CI: 16.0-21.0), respectively. his study shows that the prevalence of dermatological manifestations seems high among the hemodialysis patients in Iran, and skin discoloration, pruritus, and xerosis are more common. © 2018 Wiley Periodicals, Inc.

46 CFR 148.02-3 - Dangerous cargo manifest.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Dangerous cargo manifest. 148.02-3 Section 148.02-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES CARRIAGE OF SOLID HAZARDOUS MATERIALS IN BULK Vessel Requirements § 148.02-3 Dangerous cargo manifest. (a) Each vessel, except...

19 CFR 4.12 - Explanation of manifest discrepancy.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Explanation of manifest discrepancy. 4.12 Section 4.12 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... Explanation of manifest discrepancy. (a)(1) Vessel masters or agents shall notify the port director on Customs...

Oral manifestations of hematologic and nutritional diseases.

PubMed

Schlosser, Bethanee J; Pirigyi, Megan; Mirowski, Ginat W

2011-02-01

Oral manifestations of hematologic and nutritional deficiencies can affect the mucous membranes, teeth, periodontal tissues, salivary glands, and perioral skin. This article reviews common oral manifestations of hematologic conditions starting with disorders of the white blood cells including cyclic hematopoiesis (cyclic neutropenia), leukemias, lymphomas, plasma cell dyscrasias, and mast cell disorders; this is followed by a discussion of the impact of red blood cell disorders including anemias and less common red blood cell dyscrasias (sickle cell disease, hemochromatosis, and congenital erythropoietic porphyria) as well as thrombocytopenia. Several nutritional deficiencies exhibit oral manifestations. The authors specifically discuss the impact of water-soluble vitamins (B2, B3, B6, B9, B12, and C), fat-soluble vitamins (A, D, and K) and the eating disorders anorexia nervosa and bulimia nervosa on the oral mucosa. Copyright © 2011 Elsevier Inc. All rights reserved.

Manifest dream content as a possible predictor of suicidality.

PubMed

Glucksman, Myron L

2014-12-01

The prediction of suicidal intent remains a clinical problem. This presentation illustrates that a distinction may be made between the manifest dream reports of patients who are potentially or acutely suicidal and those who are not. A review of the literature reveals that the manifest dream reports of clinically depressed, non-suicidal individuals differ from those who are depressed and acutely suicidal. The former contain themes of loss, disappointment, rejection, helplessness, hopelessness, failure, and death. The latter contain themes of dying, death, destruction, and violence directed toward the dreamer or others, as well as hopelessness and helplessness. The author collected manifest dream reports from three clinically depressed, non-suicidal patients and three clinically depressed, potentially or acutely suicidal patients. There are apparent differences between the themes of manifest dream reports in the clinically depressed, non-suicidal patients and the clinically depressed, potentially or acutely suicidal patients. The former contain themes of death, loss, rejection, vulnerability, hopelessness, and helplessness. The latter contain themes of active harm or violence (specifically toward the dreamer), dying or being dead, aloneness, vulnerability, hopelessness, and helplessness. Clinical cases and corresponding manifest dream reports are presented. Although this is a preliminary study, it is possible that manifest dream content may be used as one of the predictors of suicidality, in conjunction with latent dream content, diagnosis, life circumstance, and clinical status.

Caffeine-induced psychiatric manifestations: a review.

PubMed

Wang, Hee Ryung; Woo, Young Sup; Bahk, Won-Myong

2015-07-01

The association between caffeine consumption and various psychiatric manifestations has long been observed. We present two cases that show the ability of caffeine to induce psychotic and manic symptoms, and we also review the extant literature on caffeine-induced psychiatric manifestations. On the basis of our own and others' findings, we suggest that caffeine may be related to not only de-novo psychotic or mood symptoms but also to aggravation of pre-existing psychotic or mood disorders. We therefore suggest that caffeine consumption among patients with mood or psychotic symptoms should be assessed carefully in clinical practice as part of routine psychiatric evaluations.

Influence of the 11-year solar cycle on the effects of the equatorial quasi-biennial oscillation, manifesting in the extratropical northern atmosphere

NASA Astrophysics Data System (ADS)

Sitnov, S. A.

2009-01-01

Using the longest and most reliable ozonesonde data sets grouped for four regions (Japan, Europe, as well as temperate and polar latitudes of Canada) the comparative analysis of regional responses of ozone, temperature, horizontal wind, tropopause and surface pressure on the equatorial quasi-biennial oscillation (QBO effects), manifesting in opposite phases of the 11-year solar cycle (11-yr SC) was carried out. The impact of solar cycle is found to be the strongest at the Canadian Arctic, near one of two climatological centres of polar vortex, where in solar maximum conditions the QBO signals in ozone and temperature have much larger amplitudes, embrace greater range of heights, and are maximized much higher than those in solar minimum conditions. The strengthening of the temperature QBO effect during solar maxima can explain why correlation between the 11-yr SC and polar winter stratospheric temperature is reversed in the opposite QBO phases. At the border of polar vortex the 11-yr SC also modulates the QBO effect in zonal wind, strengthening the quasi-biennial modulation of polar vortex during solar maxima that is associated with strong negative correlation between stratospheric QBO signals in zonal wind and temperature. Above Japan the QBO effects of ozone, temperature, and zonal wind, manifesting in solar maxima reveal the downward phase dynamics, reminding similar feature of the zonal wind in the equatorial stratosphere. Above Europe, the QBO effects in solar maxima reveal more similarity with those above Japan, while in solar minima with the effects obtained at the Canadian middle-latitude stations. It is revealed that the 11-yr SC influences regional QBO effects in tropopause height, tropopause temperature and surface pressure. The influence most distinctly manifest itself in tropopause characteristics above Japan. The results of the accompanying analysis of the QBO reference time series testify that in the period of 1965-2006 above 50-hPa level the duration

Naloxone-blocked depriming effect of anxiolytic selank on apomorphine-induced behavioral manifestations of hyperfunction of dopamine system.

PubMed

Meshavkin, V K; Kost, N V; Sokolov, O Yu; Zolotarev, Yu A; Myasoedov, N F; Zozulya, A A

2006-11-01

Peptide anxiolytic selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) applied intraperitoneally in doses of 0.01, 0.1, 1.0, and 10.0 mg/kg to mice reduces behavioral manifestations of dopaminergic system induced by apomorphine in the verticalization test. This effect was comparable to that of atypical antipsychotic olanzapine in near-therapeutic doses (0.1 and 1.0 mg/kg, intraperitoneally) and was blocked with nonselective opioid receptor antagonist naloxone (10 mg/kg, intraperitoneally). Radioreceptor assay showed that selank did not displace nonselective D2-dopamine receptor antagonist (3)H-spiperone (EC50>100 microM) and delta- and micro-opioid receptor ligand 3H-DADLE (EC50>40 microM) from specific binding sites on rat brain membranes. It is hypothesized that the revealed behavioral effect of selank is mediated by its modulating effect on the endogenous opioid system and specifically, by its effect on activity of enkephalin-degrading enzymes.

Reliability measures in item response theory: manifest versus latent correlation functions.

PubMed

Milanzi, Elasma; Molenberghs, Geert; Alonso, Ariel; Verbeke, Geert; De Boeck, Paul

2015-02-01

For item response theory (IRT) models, which belong to the class of generalized linear or non-linear mixed models, reliability at the scale of observed scores (i.e., manifest correlation) is more difficult to calculate than latent correlation based reliability, but usually of greater scientific interest. This is not least because it cannot be calculated explicitly when the logit link is used in conjunction with normal random effects. As such, approximations such as Fisher's information coefficient, Cronbach's α, or the latent correlation are calculated, allegedly because it is easy to do so. Cronbach's α has well-known and serious drawbacks, Fisher's information is not meaningful under certain circumstances, and there is an important but often overlooked difference between latent and manifest correlations. Here, manifest correlation refers to correlation between observed scores, while latent correlation refers to correlation between scores at the latent (e.g., logit or probit) scale. Thus, using one in place of the other can lead to erroneous conclusions. Taylor series based reliability measures, which are based on manifest correlation functions, are derived and a careful comparison of reliability measures based on latent correlations, Fisher's information, and exact reliability is carried out. The latent correlations are virtually always considerably higher than their manifest counterparts, Fisher's information measure shows no coherent behaviour (it is even negative in some cases), while the newly introduced Taylor series based approximations reflect the exact reliability very closely. Comparisons among the various types of correlations, for various IRT models, are made using algebraic expressions, Monte Carlo simulations, and data analysis. Given the light computational burden and the performance of Taylor series based reliability measures, their use is recommended. © 2014 The British Psychological Society.

Dermatological Manifestations in Patients Undergoing In Vitro Fertilisation: A Prospective Study.

PubMed

Sood, Aradhana; Sahu, Suvash; Karunakaran, Sandeep; Joshi, Rajneesh K; Raman, Deep Kumar

Changing sociodemographic patterns with an increase in the age of childbirth have affected fertility rates worldwide. With advancing reproductive medicine, assisted reproductive techniques (ARTs) are becoming common. While dermatological manifestations in normal pregnancies have been well documented, there is a paucity of data regarding cutaneous manifestations in patients undergoing ART. The objectives of our study were to estimate the incidence and types of dermatological manifestations in patients undergoing in vitro fertilisation (IVF) and to study their associations with age, type of infertility, and outcome of the procedure. A prospective cohort of 200 patients undergoing IVF in a tertiary care centre was observed for occurrence of any dermatological manifestations from initiation of the IVF protocol to the outcome of the procedure at 3 weeks after embryo transfer. Dermatological manifestations were seen in 27% of the study group, with urticaria being the most common cutaneous finding seen in 13.5%, followed by acneform eruptions (3%). Twenty-six (96.3%) of patients who manifested with urticaria were on progesterone. No statistically significant association was found between the occurrence of dermatological manifestations and the outcome of IVF, type of infertility, history of ART, and ovum donation in our study. Association between the age of the patient and the outcome of IVF cycle was statistically significant. Dermatological manifestations are seen in almost one-quarter of patients undergoing IVF, with progesterone-induced urticaria being the most common. Occurrence of cutaneous manifestations has no significant association with the outcome of IVF.

The Effect of Neonatal Gene Therapy on Skeletal Manifestations in Mucopolysaccharidosis VII Dogs after a Decade

PubMed Central

Xing, Elizabeth M.; Knox, Van W.; O'Donnell, Patricia A.; Sikura, Tracey; Liu, Yuli; Wu, Susan; Casal, Margret L.; Haskins, Mark E.; Ponder, Katherine P.

2013-01-01

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disease due to deficient activity of β-glucuronidase (GUSB), and results in glycosaminoglycan accumulation. Skeletal manifestations include bone dysplasia, degenerative joint disease, and growth retardation. One gene therapy approach for MPS VII involves neonatal intravenous injection of a gamma retroviral vector expressing GUSB, which results in stable expression in liver and secretion of enzyme into blood at levels predicted to be similar or higher to enzyme replacement therapy. The goal of this study was to evaluate the long-term effect of neonatal gene therapy on skeletal manifestations in MPS VII dogs. Treated MPS VII dogs could walk throughout their lives, while untreated MPS VII dogs could not stand beyond 6 months and were dead by 2 years. Luxation of the coxofemoral joint and the patella, dysplasia of the acetabulum and supracondylar ridge, deep erosions of the distal femur, and synovial hyperplasia were reduced, and the quality of articular bone was improved in treated dogs at 6 to 11 years of age compared with untreated MPS VII dogs at 2 years or less. However, treated dogs continued to have osteophyte formation, cartilage abnormalities, and an abnormal gait. Enzyme activity was found near synovial blood vessels, and there was 2% as much GUSB activity in synovial fluid as in serum. We conclude that neonatal gene therapy reduces skeletal abnormalities in MPS VII dogs, but clinically-relevant abnormalities remain. Enzyme replacement therapy will probably have similar limitations long-term. PMID:23628461

A Study of Manifestations of Extrapulmonary Tuberculosis in the ENT Region.

PubMed

Akkara, Stani Ajay; Singhania, Ankit; Akkara, Ajay George; Shah, Arti; Adalja, Mayur; Chauhan, Nirali

2014-01-01

Though tuberculosis (TB) primarily affects lungs, extra pulmonary tuberculosis (EPTB) is also common, especially in high disease load areas and mainly manifests in ENT region. To study the different manifestations of tuberculosis in ENT region in terms of presentation, disease process, treatment and outcome. Records of patients diagnosed and treated for TB in the ENT region at our institute's DOTS centre for a two and half year period were analysed for presenting complaints, examination findings, diagnostic features, treatment modes and outcome. Out of 3750 cases diagnosed as TB, 230 had EPTB. 211 cases had ENT manifestations. Majority of the cases were male and in the fourth decade of life. Commonest manifestation was cervical lymphadenopathy with 201 cases. Fine needle aspiration cytology was mostly diagnostic and category I anti TB treatment (AKT) achieved cure. The six cases of TB otitis media presented with ear discharge, sometimes bloody and had varied tympanic membrane findings and facial palsy in two cases with different types and degrees of hearing loss. Diagnosis was confirmed by histology of tissue removed during surgery. Patients completed category I AKT. Hearing and facial palsy did not improve. There were three cases of TB laryngitis and one of nasal TB both of which were confirmed by tissue diagnosis and responded well to AKT. Most of the results in the present study conform to findings of other studies. High degree of suspicion is necessary to reach diagnosis. Category I AKT is effective. Some cases may require surgery.

The NGO-ization of Community Colleges: One (More) Manifestation of Globalization

ERIC Educational Resources Information Center

Quint-Rapoport, Mia

2006-01-01

In this essay the author discusses the effects of globalization on Canadian community colleges. She applies contemporary social theories culled from the fields of feminism, geography and political science to understand one hidden manifestation of globalization in community colleges: involvement in global civil society via participation in…

Effect of met-enkephalin on chromosomal aberrations in the lymphocytes of the peripheral blood of patients with multiple sclerosis.

PubMed

Rakanović-Todić, Maida; Burnazović-Ristić, Lejla; Ibrulj, Slavka; Mulbegović, Nedžad

2014-05-01

Endogenious opiod met-enkephalin throughout previous research manifested cytoprotective and anti-inflammatory effects. Previous research suggests that met-enkephalin has cytogenetic effects. Reducement in the frequency of structural chromosome aberrations as well as a suppressive effect on lymphocyte cell cycle is found. It also reduces apoptosis in the blood samples of the patients with immune-mediated diseases. Met-enkephalin exerts immunomodulatory properties and induces stabilization of the clinical condition in patients with multiple Sclerosis (MS). The goal of the present research was to evaluate met-enkephalin in vitro effects on the number and type of chromosome aberrations in the peripheral blood lymphocytes of patients with MS. Our research detected disappearance of ring chromosomes and chromosome fragmentations in the cultures of the peripheral blood lymphocytes treated with met-enkephalin (1.2 μg/mL). However, this research did not detect any significant effects of met-enkephalin on the reduction of structural chromosome aberrations and disappearance of dicentric chromosomes. Chromosomes with the greatest percent of inclusion in chromosome aberrations were noted as: chromosome 1, chromosome 2 and chromosome 9. Additionally, we confirmed chromosome 14 as the most frequently included in translocations. Furthermore, met-enkephalin effects on the increase of the numerical aberrations in both concentrations applied were detected. Those findings should be interpreted cautiously and more research in this field should be conducted.

40 CFR 761.208 - Use of the manifest.

Code of Federal Regulations, 2012 CFR

2012-07-01

... PROHIBITIONS PCB Waste Disposal Records and Reports § 761.208 Use of the manifest. (a)(1) The generator of PCB... dilution. (ii) The PCB waste is accepted by the transporter for transport only to a storage or disposal... disposal facility listed on the manifest. (ii) The next designated transporter of PCB waste. (8) If the PCB...

40 CFR 761.208 - Use of the manifest.

Code of Federal Regulations, 2011 CFR

2011-07-01

... PROHIBITIONS PCB Waste Disposal Records and Reports § 761.208 Use of the manifest. (a)(1) The generator of PCB... dilution. (ii) The PCB waste is accepted by the transporter for transport only to a storage or disposal... disposal facility listed on the manifest. (ii) The next designated transporter of PCB waste. (8) If the PCB...

40 CFR 264.71 - Use of manifest system.

Code of Federal Regulations, 2014 CFR

2014-07-01

... revising paragraph (a)(2), and by adding paragraphs (f), (g), (h), (i), (j), and (k) to read as follows... image file of Page 1 of the manifest, or both a data string file and the image file corresponding to Page 1 of the manifest. Any data or image files transmitted to EPA under this paragraph must be...

40 CFR 761.209 - Retention of manifest records.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROHIBITIONS PCB Waste Disposal Records and Reports § 761.209 Retention of manifest records. (a) A generator of PCB waste shall keep a copy of each manifest signed in accordance with § 761.208(a)(1) until the... the PCB waste. The copy signed by the commercial storer or disposer shall be retained for at least 3...

[Otorhinolaryngological manifestations in patients with Behçet disease].

PubMed

Morales-Angulo, Carmelo; Vergara Pastrana, Sandra; Obeso-Agüera, Sergio; Acle, Leticia; González-Gay, Miguel Ángel

2014-01-01

Behçet disease (BD) is a systemic immune-mediated vasculitis of unknown origin characterised by recurrent orogenital ulceration, ocular inflammation and skin lesions. The aim of our study was to identify ear, nose and throat (ENT) manifestations associated with BD. Retrospective review of the medical records of all patients diagnosed with BD who attended a tertiary public hospital in Cantabria (Spain) over a period of 22 years. Clinical manifestations, in particular those concerning ENT, were retrieved from medical records. A medical literature review of ENT manifestations was conducted. Thirty-three patients (age range: 17-64 years) were included in the study. Most of them presented oral ulcers (97%). Eight patients (24%) presented oropharyngeal ulcers and 5 patients (15%) experienced audiovestibular symptoms (high frequency sensorineural hearing loss, vertigo and bilateral vestibular hypofunction). One patient had symptoms compatible with vestibular neuronitis as the presentation manifestation of Neuro-Behçet. In 4 patients (12%) the presence of odynophagia secondary to the presence of oropharyngeal lesions, initially interpreted as acute or recurrent tonsillitis, was the first manifestation of the disease, alone or associated with cutaneous or ocular lesions. In addition to the characteristic oral ulcers present in most patients with BD, ulcers in the oropharynx, occasionally interpreted as acute pharyngitis, are also common in these patients. Audiovestibular manifestations frequently appear during the course of the disease and may be the first symptom of central nervous system involvement. Copyright © 2013 Elsevier España, S.L. All rights reserved.

The otolaryngologic manifestations of Sotos syndrome.

PubMed

Gaudreau, Philip; Zizak, Vincent; Gallagher, Thomas Q

2013-11-01

Soto's syndrome is a genetic disorder caused by mutations in the NSD1 gene. It is characterized by excessive growth in early life. It features craniofacial abnormalities, developmental delay, hypotonia and advanced bone age. A review of the current literature reveals only chronic otitis media and conductive hearing loss as otolaryngologic manifestations of Soto's syndrome. Our objective was to determine if there are additional manifestations relevant to the otolaryngologist. We performed a retrospective case series in which the Department of Defense electronic medical record was searched for ICD 9 code 253.0 (acromegaly/gigantism). Records were reviewed for genetic testing indicative of Soto's syndrome. These records were further analyzed for evidence of otolaryngologic problems. Seventeen patients were identified with five having confirmed NSD1 mutations consistent with Soto's syndrome. Of these, 4/5 had otolaryngologic problems such as conductive hearing loss, aspiration, laryngomalacia, obstructive sleep apnea and sensorineural hearing loss. Currently there is no description in the literature of these additional manifestations of Soto's syndrome. We present this case series to support the idea that an otolaryngologist should be involved in the multidisciplinary care required for these patients. Published by Elsevier Ireland Ltd.

[Neurological manifestations of Behçet's disease].

PubMed

Noel, N; Drier, A; Wechsler, B; Piette, J-C; De Paz, R; Dormont, D; Cacoub, P; Saadoun, D

2014-02-01

Neurological manifestations of Behçet's disease (BD) occur in 5.3 to more than 50% of patients. They are divided into two major forms: "parenchymal" lesions, which include mainly meningoencephalitis as opposed to "extra-parenchymal" lesions (i.e. cerebral venous thrombosis and arterial aneurysms). Myelitis or peripheral neuropathy is exceptional. The neuro-Behçet syndrome (NBS) should be considered in the setting of neurological manifestations, particularly headache and pyramidal signs, in a young man diagnosed with BD. However, its recognition may be difficult when neurological manifestations are the presenting features of BD (one third of cases), and requires a thorough knowledge of clinical manifestations and morphological lesions. Thus, parenchymal NB lesions classically exhibit inflammatory characteristics on MRI and are located at the meso-diencephalic junction and in the brainstem, rarely with a supratentorial extension. Meningitis is not systematically associated, and may be absent in about 30% of cases. The pathogenesis of these lesions is incompletely understood, but inflammatory infiltrates include mainly neutrophils and activated T cells (mainly Th17). Differential diagnoses include infectious diseases (herpes, listeria, tuberculosis), and inflammatory diseases (i.e. multiple sclerosis and sarcoidosis). A prompt recognition of NBS should lead to initiate adequate therapies in order to limit the risk of sequelae, relapses or death. Copyright © 2013. Published by Elsevier SAS.

Oral manifestations of Diabetes Mellitus. A systematic review

PubMed Central

Mauri-Obradors, Elisabet; Estrugo-Devesa, Albert; Jané-Salas, Enric; Viñas, Miguel

2017-01-01

Background Diabetes Mellitus has become a global epidemic and presents many complications, usually proportional to the degree and duration of hyperglycemia. The aim of this systematic review was to investigate the different oral manifestations associated with Diabetes Mellitus. Material and Methods A MEDLINE search for “Diabetes Mellitus and oral manifestations” was performed. A further search was conducted for “diabetes” and its individual oral manifestation. Inclusion criteria were as follows: human clinical studies with a minimum of 30 patients; studies published in relevant scientific journals between January 1998 and January 2016. Nineteen studies fulfilled the inclusion criteria and were analyzed, assessing the strength of scientific evidence according to recommendations made by the Centre for Evidence-Based Medicine, Oxford (OCEBM), which permits adequate assessment of prevalence studies. Results A total 3,712 patients (2,084 diabetics) were included in the studies reviewed. Of the 19 studies analyzed, 4 were longitudinal studies and 15 cross-sectional studies. Periodontal disease, periapical lesions, xerostomia and taste disturbance were more prevalent among diabetic patients. An association between diabetes and caries and mucosal lesions proved positive in 5 out of 10 studies. Conclusions Despite multiple oral manifestations associated with DM, awareness of the associations between diabetes, oral health, and general health is inadequate. It is necessary for doctors and dentists to be aware of the various oral manifestations of diabetes in order to make an early diagnosis. Key words:Diabetes Mellitus, oral manifestations, oral pathology. PMID:28809366

Occupational styrene exposure induces stress-responsive genes involved in cytoprotective and cytotoxic activities.

PubMed

Strafella, Elisabetta; Bracci, Massimo; Staffolani, Sara; Manzella, Nicola; Giantomasi, Daniele; Valentino, Matteo; Amati, Monica; Tomasetti, Marco; Santarelli, Lory

2013-01-01

The aim of this study was to evaluate the expression of a panel of genes involved in toxicology in response to styrene exposure at levels below the occupational standard setting. Workers in a fiber glass boat industry were evaluated for a panel of stress- and toxicity-related genes and associated with biochemical parameters related to hepatic injury. Urinary styrene metabolites (MA+PGA) of subjects and environmental sampling data collected for air at workplace were used to estimate styrene exposure. Expression array analysis revealed massive upregulation of genes encoding stress-responsive proteins (HSPA1L, EGR1, IL-6, IL-1β, TNSF10 and TNFα) in the styrene-exposed group; the levels of cytokines released were further confirmed in serum. The exposed workers were then stratified by styrene exposure levels. EGR1 gene upregulation paralleled the expression and transcriptional protein levels of IL-6, TNSF10 and TNFα in styrene exposed workers, even at low level. The activation of the EGR1 pathway observed at low-styrene exposure was associated with a slight increase of hepatic markers found in highly exposed subjects, even though they were within normal range. The ALT and AST levels were not affected by alcohol consumption, and positively correlated with urinary styrene metabolites as evaluated by multiple regression analysis. The pro-inflammatory cytokines IL-6 and TNFα are the primary mediators of processes involved in the hepatic injury response and regeneration. Here, we show that styrene induced stress responsive genes involved in cytoprotection and cytotoxicity at low-exposure, that proceed to a mild subclinical hepatic toxicity at high-styrene exposure.

Occupational Styrene Exposure Induces Stress-Responsive Genes Involved in Cytoprotective and Cytotoxic Activities

PubMed Central

Strafella, Elisabetta; Bracci, Massimo; Staffolani, Sara; Manzella, Nicola; Giantomasi, Daniele; Valentino, Matteo; Amati, Monica; Tomasetti, Marco; Santarelli, Lory

2013-01-01

Objective The aim of this study was to evaluate the expression of a panel of genes involved in toxicology in response to styrene exposure at levels below the occupational standard setting. Methods Workers in a fiber glass boat industry were evaluated for a panel of stress- and toxicity-related genes and associated with biochemical parameters related to hepatic injury. Urinary styrene metabolites (MA+PGA) of subjects and environmental sampling data collected for air at workplace were used to estimate styrene exposure. Results Expression array analysis revealed massive upregulation of genes encoding stress-responsive proteins (HSPA1L, EGR1, IL-6, IL-1β, TNSF10 and TNFα) in the styrene-exposed group; the levels of cytokines released were further confirmed in serum. The exposed workers were then stratified by styrene exposure levels. EGR1 gene upregulation paralleled the expression and transcriptional protein levels of IL-6, TNSF10 and TNFα in styrene exposed workers, even at low level. The activation of the EGR1 pathway observed at low-styrene exposure was associated with a slight increase of hepatic markers found in highly exposed subjects, even though they were within normal range. The ALT and AST levels were not affected by alcohol consumption, and positively correlated with urinary styrene metabolites as evaluated by multiple regression analysis. Conclusion The pro-inflammatory cytokines IL-6 and TNFα are the primary mediators of processes involved in the hepatic injury response and regeneration. Here, we show that styrene induced stress responsive genes involved in cytoprotection and cytotoxicity at low-exposure, that proceed to a mild subclinical hepatic toxicity at high-styrene exposure. PMID:24086524

Succinate-based preparation alleviates manifestations of the climacteric syndrome in women.

PubMed

Peskov, A B; Maevskii, E I; Uchitel', M L; Sakharova, N Yu; Vize-Khripunova, M A

2005-09-01

Clinical placebo-controlled study of Enerlit-Clima (bioactive succinate-based food additive) a showed positive effect of the preparation on general clinical and psychoemotional manifestations of the climacteric syndrome. A trend to an increase in estradiol level in early pathological climacteric and normalization of the endometrial status were observed.

Clinical manifestations of ocular toxoplasmosis.

PubMed

Delair, Emmanuelle; Latkany, Paul; Noble, A Gwendolyn; Rabiah, Peter; McLeod, Rima; Brézin, Antoine

2011-04-01

Clinical manifestations of ocular toxoplasmosis are reviewed. Findings of congenital and acute acquired ocular toxoplasmosis include retinal scars, white-appearing lesions in the active phase often associated with vitritis. Complications can include fibrous bands, secondary serous or rhegmatogenous retinal detachments, optic neuritis and neuropathy, cataracts, increased intraocular pressure during active infection, and choroidal neovascular membranes. Recurrences in untreated congenital toxoplasmosis occur in teenage years. Manifestations at birth are less severe, and recurrences are fewer in those who were treated promptly early in the course of their disease in utero and in the first year of life. Severe retinal involvement is common at diagnosis of symptomatic congenital toxoplasmosis in the United States and Brazil. Acute acquired infections also may be complicated by toxoplasmic retinochoroiditis, with recurrences most common close to the time of acquisition. Suppressive treatment can reduce recurrent disease.

Vaccines for viral diseases with dermatologic manifestations.

PubMed

Brentjens, Mathijs H; Yeung-Yue, Kimberly A; Lee, Patricia C; Tyring, Stephen K

2003-04-01

Vaccines against infectious diseases have been available since the 1800s, when an immunization strategy against smallpox developed by Jenner gained wide acceptance. Until recently, the only vaccination strategies available involved the use of protein-based, whole killed, and attenuated live virus vaccines. These strategies have led to the development of effective vaccines against a variety of diseases with primary or prominent cutaneous manifestations. Effective and safe vaccines now used worldwide include those directed against measles and rubella (now commonly used together with a mumps vaccine as the trivalent MMR), chickenpox, and hepatitis B. The eradication of naturally occurring smallpox remains one of the greatest successes in the history of modern medicine, but stockpiles of live smallpox exist in the United States and Russia. Renewed interest in the smallpox vaccine reflects concerns about a possible bioterrorist threat using this virus. Yellow fever is a hemorrhagic virus endemic to tropical areas of South America and Africa. An effective vaccine for this virus has existed since 1937, and it is used widely in endemic areas of South America, and to a lesser extent in Africa. This vaccine is recommended once every 10 years for people who are traveling to endemic areas. Advances in immunology have led to a greater understanding of immune system function in viral diseases. Progress in genetics and molecular biology has allowed researchers to design vaccines with novel mechanisms of action (eg, DNA, vector, and VLP vaccines). Vaccines have also been designed to specifically target particular viral components, allowing for stimulation of various arms of the immune system as desired. Ongoing research shows promise in prophylactic and therapeutic vaccination for viral infections with cutaneous manifestations. Further studies are necessary before vaccines for HSV, HPV, and HIV become commercially available.

46 CFR 148.71 - Information included in the dangerous cargo manifest.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Information included in the dangerous cargo manifest. 148.71 Section 148.71 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS... § 148.71 Information included in the dangerous cargo manifest. The dangerous cargo manifest must include...

46 CFR 148.71 - Information included in the dangerous cargo manifest.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Information included in the dangerous cargo manifest. 148.71 Section 148.71 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS... § 148.71 Information included in the dangerous cargo manifest. The dangerous cargo manifest must include...

46 CFR 148.71 - Information included in the dangerous cargo manifest.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Information included in the dangerous cargo manifest. 148.71 Section 148.71 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS... § 148.71 Information included in the dangerous cargo manifest. The dangerous cargo manifest must include...

46 CFR 148.71 - Information included in the dangerous cargo manifest.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Information included in the dangerous cargo manifest. 148.71 Section 148.71 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS... § 148.71 Information included in the dangerous cargo manifest. The dangerous cargo manifest must include...

40 CFR 265.71 - Use of manifest system.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., § 265.71 was amended by revising paragraph (a)(2), and by adding paragraphs (f), (g), (h), (i), (j), and... operator, the owner or operator may transmit to the system operator an image file of Page 1 of the manifest, or both a data string file and the image file corresponding to Page 1 of the manifest. Any data or...

Neurologic manifestations of chronic methamphetamine abuse

PubMed Central

Rusyniak, Daniel E.

2011-01-01

Summary Chronic methamphetamine abuse has devastating effects on the central nervous system. The degree to which addicts will tolerate the dysfunction in the way they think, feel, move, and even look, is a powerful testimony to the addictive properties of this drug. While the mechanisms behind these disorders are complex, at their heart they involve the recurring increase in the concentrations of central monoamines with subsequent dysfunction in dopaminergic neurotransmission. The mainstay of treatment for the problems associated with chronic methamphetamine abuse is abstinence. However, by recognizing the manifestations of chronic abuse, clinicians will be better able to help their patients get treatment for their addiction and to deal with the neurologic complications related to chronic abuse. PMID:21803215

Skin manifestations of chronic kidney disease.

PubMed

Robles-Mendez, J C; Vazquez-Martinez, O; Ocampo-Candiani, J

2015-10-01

Skin manifestations associated with chronic kidney disease are very common. Most of these conditions present in the end stages and may affect the patient's quality of life. Knowledge of these entities can contribute to establishing an accurate diagnosis and prognosis. Severe renal pruritus is associated with increased mortality and a poor prognosis. Nail exploration can provide clues about albumin and urea levels. Nephrogenic systemic fibrosis is a preventable disease associated with gadolinium contrast. Comorbidities, such as diabetes mellitus and secondary hyperparathyroidism, can lead to acquired perforating dermatosis and calciphylaxis, respectively. Effective and innovative treatments are available for all of these conditions. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Management and outcome of cervical versus intrathoracic manifestation of cervical anastomotic leakage after transthoracic esophagectomy for cancer.

PubMed

van Rossum, Peter S N; Haverkamp, Leonie; Carvello, Michele; Ruurda, Jelle P; van Hillegersberg, Richard

2017-01-01

The aim of this study was to evaluate management strategies and related outcomes for cervical versus intrathoracic manifestation of cervical anastomotic leakage after transthoracic esophagectomy for cancer with gastric conduit reconstruction. Patients with esophageal cancer undergoing transthoracic esophagectomy with cervical anastomosis from October 2003 to December 2014 were identified from a prospectively acquired database. Management strategies and related outcomes among patients with anastomotic leakage confined to the neck were compared to patients with intrathoracic manifestation of anastomotic leakage. From a total of 286 patients, leakage of the cervical anastomosis occurred in 60 patients (21%) at a median time of 7 days after esophagectomy. Leakage was confined to the neck in 23 of 60 patients (38%), whereas 37 of 60 patients (62%) presented with intrathoracic spread. Leakages with intrathoracic manifestation were more frequently accompanied by a positive SIRS score compared to leakages confined to the neck (73% vs. 35%, respectively; P = 0.004). Drainage of the anastomotic leakage through the neck wound was effective in all of 23 patients (100%) with cervical manifestation. In patients with intrathoracic manifestation, mediastinal drainage through the neck was successful in 15 of 37 patients (41%), whereas 22 patients (59%) required an intervention through the thoracic cavity. Compared to patients with leakage confined to the neck, patients with intrathoracic manifestation showed prolonged intensive care unit (ICU) stay (median 6 vs. 2 days, respectively; P = 0.001), hospital stay (median 34 vs. 19 days, respectively; P < 0.001), and time to oral intake (32 vs. 23 days, respectively; P = 0.018). Intrathoracic manifestation of cervical anastomotic leakage occurs in more than half of patients with anastomotic leakage after transthoracic esophagectomy for cancer. A SIRS reaction should raise the suspicion of intrathoracic spread of

8 CFR 251.5 - Paper arrival and departure manifests for crew.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 8 Aliens and Nationality 1 2011-01-01 2011-01-01 false Paper arrival and departure manifests for... REGULATIONS ARRIVAL AND DEPARTURE MANIFESTS AND LISTS: SUPPORTING DOCUMENTS § 251.5 Paper arrival and... from the United States must submit arrival and departure manifests in a paper format in accordance with...

Hyperoside prevents oxidative damage induced by hydrogen peroxide in lung fibroblast cells via an antioxidant effect.

PubMed

Piao, Mei Jing; Kang, Kyoung Ah; Zhang, Rui; Ko, Dong Ok; Wang, Zhi Hong; You, Ho Jin; Kim, Hee Sun; Kim, Ju Sun; Kang, Sam Sik; Hyun, Jin Won

2008-12-01

We elucidated the cytoprotective effects of hyperoside (quercetin-3-O-galactoside) against hydrogen peroxide (H2O2)-induced cell damage. We found that hyperoside scavenged the intracellular reactive oxygen species (ROS) detected by fluorescence spectrometry, flow cytometry, and confocal microscopy. In addition, we found that hyperoside scavenged the hydroxyl radicals generated by the Fenton reaction (FeSO4)+H2O2) in a cell-free system, which was detected by electron spin resonance (ESR) spectrometry. Hyperoside was found to inhibit H2O2-induced apoptosis in Chinese hamster lung fibroblast (V79-4) cells, as shown by decreased apoptotic nuclear fragmentation, decreased sub-G(1) cell population, and decreased DNA fragmentation. In addition, hyperoside pretreatment inhibited the H2O2-induced activation of caspase-3 measured in terms of levels of cleaved caspase-3. Hyperoside prevented H2O2-induced lipid peroxidation as well as protein carbonyl. In addition, hyperoside prevented the H2O2-induced cellular DNA damage, which was established by comet tail, and phospho histone H2A.X expression. Furthermore, hyperoside increased the catalase and glutathione peroxidase activities. Conversely, the catalase inhibitor abolished the cytoprotective effect of hyperoside from H2O2-induced cell damage. In conclusion, hyperoside was shown to possess cytoprotective properties against oxidative stress by scavenging intracellular ROS and enhancing antioxidant enzyme activity.

The effect of neonatal gene therapy on skeletal manifestations in mucopolysaccharidosis VII dogs after a decade.

PubMed

Xing, Elizabeth M; Knox, Van W; O'Donnell, Patricia A; Sikura, Tracey; Liu, Yuli; Wu, Susan; Casal, Margret L; Haskins, Mark E; Ponder, Katherine P

2013-06-01

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disease due to deficient activity of β-glucuronidase (GUSB), and results in glycosaminoglycan accumulation. Skeletal manifestations include bone dysplasia, degenerative joint disease, and growth retardation. One gene therapy approach for MPS VII involves neonatal intravenous injection of a gamma retroviral vector expressing GUSB, which results in stable expression in liver and secretion of enzyme into blood at levels predicted to be similar or higher to enzyme replacement therapy. The goal of this study was to evaluate the long-term effect of neonatal gene therapy on skeletal manifestations in MPS VII dogs. Treated MPS VII dogs could walk throughout their lives, while untreated MPS VII dogs could not stand beyond 6 months and were dead by 2 years. Luxation of the coxofemoral joint and the patella, dysplasia of the acetabulum and supracondylar ridge, deep erosions of the distal femur, and synovial hyperplasia were reduced, and the quality of articular bone was improved in treated dogs at 6 to 11 years of age compared with untreated MPS VII dogs at 2 years or less. However, treated dogs continued to have osteophyte formation, cartilage abnormalities, and an abnormal gait. Enzyme activity was found near synovial blood vessels, and there was 2% as much GUSB activity in synovial fluid as in serum. We conclude that neonatal gene therapy reduces skeletal abnormalities in MPS VII dogs, but clinically-relevant abnormalities remain. Enzyme replacement therapy will probably have similar limitations long-term. Copyright © 2013 Elsevier Inc. All rights reserved.

Neurologic manifestations of major electrolyte abnormalities.

PubMed

Diringer, M

2017-01-01

The brain operates in an extraordinarily intricate environment which demands precise regulation of electrolytes. Tight control over their concentrations and gradients across cellular compartments is essential and when these relationships are disturbed neurologic manifestations may develop. Perturbations of sodium are the electrolyte disturbances that most often lead to neurologic manifestations. Alterations in extracellular fluid sodium concentrations produce water shifts that lead to brain swelling or shrinkage. If marked or rapid they can result in profound changes in brain function which are proportional to the degree of cerebral edema or contraction. Adaptive mechanisms quickly respond to changes in cell size by either increasing or decreasing intracellular osmoles in order to restore size to normal. Unless cerebral edema has been severe or prolonged, correction of sodium disturbances usually restores function to normal. If the rate of correction is too rapid or overcorrection occurs, however, new neurologic manifestations may appear as a result of osmotic demyelination syndrome. Disturbances of magnesium, phosphate and calcium all may contribute to alterations in sensorium. Hypomagnesemia and hypocalcemia can lead to weakness, muscle spasms, and tetany; the weakness from hypophosphatemia and hypomagnesemia can impair respiratory function. Seizures can be seen in cases with very low concentrations of sodium, magnesium, calcium, and phosphate. © 2017 Elsevier B.V. All rights reserved.

Clinical manifestations of food allergy.

PubMed

Perry, Tamara T; Pesek, Robbie D

2013-06-01

Adverse reactions to foods are a diverse group of clinical syndromes resulting from immunologic and non-immunologic responses to food ingestion. Symptoms can range from mild, self-limiting reactions to severe, life-threatening reactions depending on the mechanism. This review primarily focuses on the clinical manifestations of immunologically derived adverse food reactions or food allergies.The true prevalence of food allergy is unknown. Up to 25% of the general population believes that they may be allergic to some food; however, the actual prevalence of food allergy diagnosed by a provider appears to be 1.5% to 2% of the adult population and approximately 6% to 8% of children. This discrepancy makes it imperative that clinicians are aware of the different food allergy syndromes. With a clear understanding of the clinical manifestations of food allergies, an accurate diagnosis and treatment plan can be formulated. Failing to do so may result in unnecessary dietary restrictions that may adversely affect nutritional status, growth, and quality of life.Most food allergic reactions are secondary to a limited number of foods, and the most common foods causing allergic reactions in children include milk, egg, peanuts, tree nuts, and fish. In adolescents and adults, allergies to peanuts, tree nuts, fish, and shellfish are most prevalent. Food allergies can result from immunoglobulin E (IgE)-mediated, non-IGE-mediated, or mixed IgE/non-IgE mechanisms. The purpose of this review is to discuss the clinical manifestations of each of these types of food allergy. Copyright 2013, SLACK Incorporated.

10 CFR 20.2006 - Transfer for disposal and manifests.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Transfer for disposal and manifests. 20.2006 Section 20.2006 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2006 Transfer for disposal and manifests. (a) The requirements of this section and appendix G to...

10 CFR 20.2006 - Transfer for disposal and manifests.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Transfer for disposal and manifests. 20.2006 Section 20.2006 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2006 Transfer for disposal and manifests. (a) The requirements of this section and appendix G to...

10 CFR 20.2006 - Transfer for disposal and manifests.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Transfer for disposal and manifests. 20.2006 Section 20.2006 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2006 Transfer for disposal and manifests. (a) The requirements of this section and appendix G to...

10 CFR 20.2006 - Transfer for disposal and manifests.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Transfer for disposal and manifests. 20.2006 Section 20.2006 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2006 Transfer for disposal and manifests. (a) The requirements of this section and appendix G to...

10 CFR 20.2006 - Transfer for disposal and manifests.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Transfer for disposal and manifests. 20.2006 Section 20.2006 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2006 Transfer for disposal and manifests. (a) The requirements of this section and appendix G to...

[Clinical manifestations of neurocysticercosis].

PubMed

San-juan Orta, D

2009-06-01

Cysticercosis is a common parasitic infection caused by the larval phase of the Taenia solium, it infects humans as well as pigs. Considered an endemic parasitosis in developing countries including Latin America, Asia and Africa. Clinical manifestations of the disease can be influenced by ambient factors, host individualities and the infectious agent itself. Neurocysticercosis can be asymptomatic or present with various signs and symptoms that can vary in severity. This review is focused on analyzing the various presentations of Neurocysticercosis throughout different age groups, and special populations. We found asymptomatic presentations to be the most common form, followed by various grades of severity including in its most severe form death. The most common alterations include: epilepsy (60-90%), intracraneal hypertension (14-27%), as well as neuropsychiatric symptoms (5-52%), and focal neurological deficits (4-19%). The heterogeneity of the clinical scenario relies upon parasite factors (number, localization and stage of central nervous system [CNS] disease), host particularities (gender, age and immunologic response), and finally environmental factors. The most common form of infection is asymptomatic although there are various forms of clinical manifestations that rely upon different factors including environment, host response and the parasite itself.

Are Systemic Manifestations Ascribable to COPD in Smokers? A Structural Equation Modeling Approach.

PubMed

Boyer, Laurent; Bastuji-Garin, Sylvie; Chouaid, Christos; Housset, Bruno; Le Corvoisier, Philippe; Derumeaux, Geneviève; Boczkowski, Jorge; Maitre, Bernard; Adnot, Serge; Audureau, Etienne

2018-06-05

Whether the systemic manifestations observed in Chronic Obstructive Pulmonary Disease (COPD) are ascribable to lung dysfunction or direct effects of smoking is in debate. Structural Equations Modeling (SEM), a causal-oriented statistical approach, could help unraveling the pathways involved, by enabling estimation of direct and indirect associations between variables. The objectives of the study was to investigate the relative impact of smoking and COPD on systemic manifestations, inflammation and telomere length. In 292 individuals (103 women; 97 smokers with COPD, 96 smokers without COPD, 99 non-smokers), we used SEM to explore the pathways between smoking (pack-years), lung disease (FEV 1 , K CO ), and the following parameters: arterial stiffness (aortic pulse wave velocity, PWV), bone mineral density (BMD), appendicular skeletal muscle mass (ASMM), grip strength, insulin resistance (HOMA-IR), creatinine clearance (eGFR), blood leukocyte telomere length and inflammatory markers (Luminex assay). All models were adjusted on age and gender. Latent variables were created for systemic inflammation (inflammatory markers) and musculoskeletal parameters (ASMM, grip strength, BMD). SEM showed that most effects of smoking were indirectly mediated by lung dysfunction: e.g. via FEV 1 on musculoskeletal factor, eGFR, HOMA-IR, PWV, telomere length, CRP, white blood cells count (WBC) and inflammation factor, and via K CO on musculoskeletal factor, eGFR and PWV. Direct effects of smoking were limited to CRP and WBC. Models had excellent fit. In conclusion, SEM highlighted the major role of COPD in the occurrence of systemic manifestations while smoking effects were mostly mediated by lung function.

Personality disorders among alcohol-dependent patients manifesting or not manifesting cocaine abuse: a comparative pilot study.

PubMed

Echeburúa, Enrique; De Medina, Ricardo Bravo; Aizpiri, Javier

2009-01-01

This study assessed personality disorders (PDs) in 158 alcohol-dependent outpatients (62 manifesting cocaine abuse and 96 without cocaine abuse) with the International Personality Disorders Examination interview between 2003 and 2006. Thirty-nine alcohol-dependent/cocaine abusers (62.9% of this group) and 51 only alcohol-dependent patients (53.1% of this group) manifested at least one PD. There were no statistically significant differences between groups in the overall prevalence rate of PDs. The most prevalent PDs, among the alcohol-dependent/cocaine abusers, were antisocial (21%), narcissistic (14.5%), and borderline (11.3%) PDs. The most frequently diagnosed PDs among the only alcohol-dependent patients were obsessive-compulsive (20.8%), paranoid (10.4%), and dependent (9.4%) PDs. There were significant differences between the groups. The study limitations are discussed.

Transport stress induces heart damage in newly hatched chicks via blocking the cytoprotective heat shock response and augmenting nitric oxide production.

PubMed

Sun, F; Zuo, Y-Z; Ge, J; Xia, J; Li, X-N; Lin, J; Zhang, C; Xu, H-L; Li, J-L

2018-04-20

Transport stress affects the animal's metabolism and psychological state. As a pro-survival pathway, the heat shock response (HSR) protects healthy cells from stressors. However, it is unclear whether the HSR plays a role in transport stress-induced heart damage. To evaluate the effects of transport stress on heart damage and HSR protection, newly hatched chicks were treated with transport stress for 2 h, 4 h and 8 h. Transport stress caused decreases in body weight and increases in serum creatine kinase (CK) activity, nitric oxide (NO) content in heart tissue, cardiac nitric oxide syntheses (NOS) activity and NOS isoforms transcription. The mRNA expression of heat shock factors (HSFs, including HSF1-3) and heat shock proteins (HSPs, including HSP25, HSP40, HSP47, HSP60, HSP70, HSP90 and HSP110) in the heart of 2 h transport-treated chicks was upregulated. After 8 h of transport stress in chicks, the transcription levels of the same HSPs and HSF2 were reduced in the heart. It was also found that the changes in the HSP60, HSP70 and HSP90 protein levels had similar tendencies. These results suggested that transport stress augmented NO generation through enhancing the activity of NOS and the transcription of NOS isoforms. Therefore, this study provides new evidence that transport stress induces heart damage in the newly hatched chicks by blocking the cytoprotective HSR and augmenting NO production.

Rheumatological manifestations in inflammatory bowel disease

PubMed Central

Voulgari, Paraskevi V.

2011-01-01

Rheumatological manifestations in inflammatory bowel disease (IBD) are frequent and include peripheral arthritis, axial involvement and peripheral enthesitis. Secondary osteoporosis and hypertrophic osteoarthropathy may also occur. Complications of IBD (e.g. septic arthritis) must be distinguished from sterile inflammation. Adverse effects of corticosteroid treatment, such as osteonecrosis, may also affect joints. Axial involvement ranges from low back pain to true ankylosing spondylitis. Human leukocyte antigen B27 is associated with axial involvement of IBD. Peripheral arthritis has been classified into two types. Type I is a pauciarticular, asymmetric usually non destructive arthritis affecting large joints and is usually associated with active bowel disease. Type II is a polyarthritis affecting small joints and tends to run a course independent of the bowel disease. Treatment of joint symptoms in IBD include sulphasalazine, azathioprine, methotrexate and glucocorticoids. Anti-tumor necrosis factor antibodies are effective in treating resistant or complicated Crohn’s disease as well as peripheral arthritis and axial involvement. PMID:24713717

Otolaryngic manifestations of Cushing disease.

PubMed

Kuan, Edward C; Peng, Kevin A; Suh, Jeffrey D; Bergsneider, Marvin; Wang, Marilene B

2017-08-01

Cushing disease is a relatively rare cause of Cushing syndrome secondary to a hyperfunctioning pituitary adenoma. In addition to signs and symptoms of hypercortisolism, Cushing disease may present with diverse otolaryngic manifestations, which may guide diagnosis and management. We performed a retrospective chart review of patients who were found to have Cushing disease and who underwent transnasal transsphenoidal surgery for pituitary adenomas between January 1, 2007, and July 1, 2014, at a tertiary academic medical center. There were 37 consecutive patients in this series with Cushing disease caused by a pituitary adenoma. Fifteen (41%) patients complained of visual changes. Five (14%) patients suffered from obstructive sleep apnea. Four (11%) patients had thyroid disease. Other symptoms included hearing loss, vertigo, tinnitus, epistaxis, dysphagia, and salivary gland swelling. Although Cushing disease traditionally presents with classic "Cushingoid" systemic features, it also may present with various otolaryngic manifestations. A thorough workup by otolaryngologists is critical in the comprehensive management of these patients.

Clinical manifestations of tension pneumothorax: protocol for a systematic review and meta-analysis

PubMed Central

2014-01-01

random effects models (for observational studies) and generalized estimating equations adjusted for reported potential confounding factors (for case reports and series). Discussion This study will compile the world literature on tension pneumothorax and provide the first systematic description of the clinical manifestations of the disorder according to presenting patient respiratory status. It will also demonstrate a series of methods that may be used to address difficulties likely to be encountered during the conduct of a meta-analysis of data contained in published case reports and series. PROSPERO registration number: CRD42013005826. PMID:24387082

The vestibulocochlear bases for wartime posttraumatic stress disorder manifestations.

PubMed

Tigno, T A; Armonda, R A; Bell, R S; Severson, M A

2017-09-01

Preliminary findings based on earlier retrospective studies of 229 wartime head injuries managed by the Walter Reed Army Medical Center (WRAMC)/National Naval Medical Center (NNMC) Neurosurgery Service during the period 2003-08 detected a threefold rise in Posttraumatic Stress Disorder (PTSD) manifestations (10.45%) among Traumatic Brain Injuries (TBI) having concomitant vestibulocochlear injuries compared to 3% for the TBI group without vestibulo-cochlear damage (VCD), prompting the authors to undertake a more focused study of the vestibulo-auditory pathway in explaining the development of posttraumatic stress disorder manifestations among the mostly Blast-exposed head-injured. The subsequent historical review of PTSD pathophysiology studies, the evidence for an expanded vestibular system and of a dominant vestibular system, the vascular vulnerability of the vestibular nerves in stress states as well as the period of cortical imprinting has led to the formation of a coherent hypotheses utilizing the vestibulocochlear pathway in understanding the development of PTSD manifestations. Neuroimaging and neurophysiologic tests to further validate the vestibulocochlear concept on the development of PTSD manifestations are proposed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Current management of sarcoidosis I: pulmonary, cardiac, and neurologic manifestations.

PubMed

West, Sterling G

2018-05-01

Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation of multiple organ systems. Pulmonary, cardiac, and neurologic involvements have the worst prognosis. Current recommendations for the therapeutic management and follow-up of sarcoidosis involving these critical organs will be reviewed. In those sarcoidosis patients requiring immunosuppressive therapy, corticosteroids are used first at varying doses depending on the presenting manifestation. Patients with symptomatic pulmonary, cardiac, or neurologic involvement will be maintained on corticosteroids for at least a year. Many require a second immunosuppressive agent with methotrexate used most commonly. Anti-tumor necrosis factor agents, especially infliximab, are effective and recommendations for their use have been proposed. Evidence-based treatment guidelines do not exist for most sarcoidosis clinical manifestations. Therefore, clinical care of these patients must rely on expert opinion. Patients are best served by a multidisciplinary approach to their care. Future research to identify environmental triggers, genetic associations, biomarkers for treatment response, and where to position new steroid-sparing immunosuppressive agents is warranted.

Renal manifestations of primary mitochondrial disorders

PubMed Central

Finsterer, Josef; Scorza, Fulvio

2017-01-01

The aim of the present review was to summarize and discuss previous findings concerning renal manifestations of primary mitochondrial disorders (MIDs). A literature review was performed using frequently used databases. The study identified that primary MIDs frequently present as mitochondrial multiorgan disorder syndrome (MIMODS) at onset or in the later course of the MID. Occasionally, the kidneys are affected in MIDs. Renal manifestations of MIDs include renal insufficiency, nephrolithiasis, nephrotic syndrome, renal cysts, renal tubular acidosis, Bartter-like syndrome, Fanconi syndrome, focal segmental glomerulosclerosis, tubulointerstitial nephritis, nephrocalcinosis, and benign or malign neoplasms. Among the syndromic MIDs, renal involvement has been most frequently reported in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome, Kearns-Sayre syndrome, Leigh syndrome and mitochondrial depletion syndromes. Only in single cases was renal involvement also reported in chronic progressive external ophthalmoplegia, Pearson syndrome, Leber's hereditary optic neuropathy, coenzyme-Q deficiency, X-linked sideroblastic anemia and ataxia, myopathy, lactic acidosis, and sideroblastic anemia, pyruvate dehydrogenase deficiency, growth retardation, aminoaciduria, cholestasis, iron overload, lactacidosis, and early death, and hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis syndrome. The present study proposes that the frequency of renal involvement in MIDs is probably underestimated. Diagnosis of renal involvement follows general guidelines and treatment is symptomatic. Thus, renal manifestations of primary MIDs require recognition and appropriate management, as they determine the outcome of MID patients. PMID:28515908

NRC`s proposed rulemaking on the documentation and reporting of low-level radioactive waste shipment manifest information

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

Lahs, W.R.; Haisfield, M.F.

1991-12-31

Since the 1982 promulgation of regulations for the land disposal of low-level radioactive waste (LLW), requirements have been in place to control transfers of LLW intended for disposal at licensed land disposal facilities. These requirements established a manifest tracking system and defined processes to control transfers of LLW intended for disposal at a land disposal facility. Because the regulations did not specify the format for the LLW shipment manifests, it was not unexpected that the two operators of the three currently operating disposal sites should each have developed their own manifest forms. The forms have many similarities and the collectedmore » information, in many cases, is identical; however, these manifests incorporate unique operator preferences and also reflect the needs of the Agreement State regulatory authority in the States where the disposal sites are located. Since Agreement State regulations must be compatible with, but need not always be identical to, those of the Nuclear Regulatory Commission (NRC), the possibility of a proliferation of different manifest forms containing variations in collected information could be envisioned. If these manifests were also to serve a shipping paper purpose, effective integration of the Department of Transportations` (DOT) requirements would also have to be addressed. This wide diversity in uses of manifest information by Federal and State regulatory authorities, other State or Compact entities, and disposal site operators, suggested a single consolidated approach to develop a uniform manifest format with a baseline information content and to define recordkeeping requirements. The NRC, in 1989, had embarked on a rulemaking activity to establish a base set of manifest information needs for regulatory purposes. In response to requests from State and Regional Compact organizations who are attempting to design, develop and operate LLW disposal facilities, and with the general support of Agreement State

Endothelial cytoprotection from oxidized LDL by some crude Melanesian plant extracts is not related to their antioxidant capacity.

PubMed

Owen, Patrick L; Matainaho, Teatulohi; Sirois, Martin; Johns, Timothy

2007-01-01

Habitual consumption of some Melanesian medicinal and food plants may influence atherosclerosis development via their antioxidant capacity at the endothelial level. Areca nut (AN; Areca catechu), piper inflorescence (PBI; Piper betle), betel quid (BQ), guava buds (GB; Psidium guajava), the leaves (NL), juice (NJ), fruit (NF), and root (NR) of noni (Morinda citrifolia), the propagules of raw (MBR), and cooked (MBC) mangrove (Bruguiera gymnorrhiza) were evaluated for their ability to scavenge the 1,1-diphenyl-2-picryl-hydrazyle (DPPH) radical, to protect human low-density lipoprotein (LDL) from Cu2+-catalyzed oxidation and to protect cultured bovine aortal endothelial cells (BAEC) from oxidized LDL (oxLDL)-induced cytotoxicity. Polyphenol-rich extracts AN, PBI, and BQ were potent DPPH scavengers, having similar activity to quercetin and able to protect LDL from oxidation in a dose-dependent manner at concentrations higher than 10 microg/mL, but were pro-oxidants at lower concentrations. These extracts were cytotoxic to BAEC at concentrations above 10 microg/mL and were unable to prevent oxLDL endotheliopathy. GB and NR at 10 mug/mL displayed both the ability to delay LDL oxidation and prevent oxLDL cytotoxicity, although the latter lacked the ability to scavenge the DPPH radical. At higher concentrations, however, both were cytotoxic in themselves. The remaining noni extracts NF, NJ, NL, and both mangrove extracts MBC and MBR were unable to protect LDL from oxidation at all tested concentrations, but were effective cytoprotective agents at 50 microg/mL. All extracts were able to prevent an oxLDL-mediated increase in intracellular aldehyde generation but had little effect on extracellular peroxidation as measured by thiobarbituric acid reactive substances (TBARS). On the basis of this model system, we conclude that the antioxidant benefits of AN, PBI, and BQ may be offset by their enhancement of their cytotoxic effects of oxLDL toward BAEC, whereas GB and low

Testing manifest monotonicity using order-constrained statistical inference.

PubMed

Tijmstra, Jesper; Hessen, David J; van der Heijden, Peter G M; Sijtsma, Klaas

2013-01-01

Most dichotomous item response models share the assumption of latent monotonicity, which states that the probability of a positive response to an item is a nondecreasing function of a latent variable intended to be measured. Latent monotonicity cannot be evaluated directly, but it implies manifest monotonicity across a variety of observed scores, such as the restscore, a single item score, and in some cases the total score. In this study, we show that manifest monotonicity can be tested by means of the order-constrained statistical inference framework. We propose a procedure that uses this framework to determine whether manifest monotonicity should be rejected for specific items. This approach provides a likelihood ratio test for which the p-value can be approximated through simulation. A simulation study is presented that evaluates the Type I error rate and power of the test, and the procedure is applied to empirical data.

Diabetic neuropathy: Clinical manifestations and current treatments

PubMed Central

Callaghan, Brian C.; Cheng, Hsinlin; Stables, Catherine L.; Smith, Andrea L.; Feldman, Eva L.

2014-01-01

Diabetic peripheral neuropathy is a prevalent, disabling condition. The most common manifestation is a distal symmetric polyneuropathy (DSP), but many patterns of nerve injury can occur. Currently, the only effective treatments are glucose control and pain management. While glucose control dramatically decreases the development of neuropathy in those with type 1 diabetes, the effect is likely much smaller in those with type 2 diabetes. High levels of evidence support the use of certain anticonvulsants and antidepressants for pain management in diabetic peripheral neuropathy. However, the lack of disease modifying therapies for diabetic DSP makes the identification of new modifiable risk factors essential. Intriguingly, growing evidence supports an association between metabolic syndrome components, including pre-diabetes, and neuropathy. Future studies are needed to further explore this relationship with implications for new treatments for this common disease. PMID:22608666

Dermatomal Sensory Manifestations in Opalski Syndrome.

PubMed

Kon, Tomoya; Funamizu, Yukihisa; Ueno, Tatsuya; Haga, Rie; Nishijima, Haruo; Arai, Akira; Suzuki, Chieko; Nunomura, Jinichi; Baba, Masayuki; Tomiyama, Masahiko

2017-01-01

A 31-year-old Japanese woman presented with sudden-onset unstable gait followed by nuchal pain. A neurological examination revealed right-sided limb weakness and decreased pain and thermal sensation on the left side below the level of the L1 dermatome. A lower lateral medullary infarction with ipsilateral hemiplegia, known as Opalski syndrome, caused by spontaneous vertebral artery dissection was diagnosed by magnetic resonance imaging. The spinothalamic tract in the medulla oblongata has a topographic arrangement of sensory fibers, and the dermatomal sensory deficit in this case can be explained in relation to that. This is the first reported case of Opalski syndrome with dermatomal sensory manifestations. Opalski syndrome could be a differential diagnosis for dermatomal sensory manifestations. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Lenalidomide for refractory cutaneous manifestations of pediatric systemic lupus erythematosus.

PubMed

Wu, E Y; Schanberg, L E; Wershba, E C; Rabinovich, C E

2017-05-01

Objective Cutaneous manifestations of pediatric systemic lupus erythematosus cause significant morbidity. Lenalidomide, a thalidomide analogue, has shown promise treating cutaneous lupus erythematosus in adults. Our objective was to evaluate lenalidomide's efficacy and safety in treating refractory cutaneous manifestations of pediatric systemic lupus erythematosus. Methods We performed a retrospective chart review of 10 adolescents who received lenalidomide for recalcitrant cutaneous lupus erythematosus. Information was gathered at drug initiation and 6-month follow-up. The Wilcoxon matched-pairs signed-rank test was used to assess change in quantitative parameters of disease activity. Results Nine subjects were girls and six were African-American. Indications for lenalidomide treatment included alopecia, nasal and oral ulcers, extensive malar rash, discoid lesions, bullous lesions, panniculitis, cutaneous vasculitis, and Raynaud's phenomenon with digital ulcerations. Within 6 months, all patients demonstrated complete or near resolution based on physician report. Prednisone dose decreased from a mean 23.5 mg (SD± 13.3) to 12.25 mg (SD± 9.2) ( P= 0.008). Sedimentation rate decreased from a mean 29 mm/hour (SD± 31.5) to 17 mm/hour (SD± 18.1) ( P= 0.004). Lenalidomide was well tolerated. Conclusion Lenalidomide is an effective and safe treatment for a spectrum of dermatological conditions in pediatric systemic lupus erythematosus. Its use may allow a reduction in prednisone dose and decreased disfigurement. Prospective study is needed to clarify lenalidomide's role in treating cutaneous manifestations of systemic lupus erythematosus.

[Respiratory manifestations of yellow nail syndrome: report of two cases and literature review].

PubMed

Li, S; Huang, H; Xu, K; Xu, Z J

2018-03-12

Objective: To describe the clinical characteristics of respiratory manifestations of yellow nail syndrome. Methods: We conducted a retrospective analysis of 2 patients with respiratory diseases associated with yellow nail syndrome. Their clinical and chest radiological data were collected. We searched PubMed, Wanfang and CNKI databases with the keywords "yellow nail syndrome, yellow nail and lung" in Chinese and English. And the relevant literatures, including 6 articles in Chinese and 81 articles in English, were reviewed. Results: Our 2 patients were male, one 60 years old and the other 76. Typical yellow nails were present in their fingers, and one of them also showed toe yellow nails. One patient was admitted for refractory respiratory infection and he was diagnosed with diffuse bronchiectasis. The respiratory symptoms could be relieved with antibiotics according to the results of sputum microbiological analysis. The other patient was admitted for cough and exertional dyspnea, and refractory pleural effusions were revealed bilaterally. He received repeated effusion drainage by thoracentesis, and Octreotide was tried recently. A total of 373 cases were reviewed in Chinese and English literatures. Pleural effusions (152 cases) and diffuse bronchiectasis (121 cases) were the most common reported respiratory manifestations. Lymphoedema was present in almost all cases with pleural effusion associated with yellow nail syndrome, and the effusion was usually exudative and lymphocyte predominant. Pleurodesis and decortication were effective for them. But, somatostatin analogues had been tried effectively for these patients recently. On the other hand, literatures showed that diffuse bronchiectasis in yellow nail syndrome was less severe than idiopathic diffuse bronchiectasis, and might benefit from long-term macrolide antibiotics. Conclusions: Yellow nail syndrome is a very rare disorder. Besides yellow nail, respiratory manifestations are the main clinical

MRI and clinical manifestations of delayed encephalopathy after carbon monoxide poisoning.

PubMed

Wang, Xiahong; Li, Zhenyu; Berglass, Jacqueline; He, Wenlong; Zhao, Jianmin; Zhang, Min; Gao, Chongyang; Zhang, Caixia; Zhang, Huimin; Yi, Xuewei

2016-11-01

To explore the relationship between the clinical manifestations and functional magnetic resonance images of delayed encephalopathy after carbon monoxide intoxication. Six patients received the MRI were diagnosed with delayed encephalopathy after carbon monoxide (CO) poisoning. Clinical manifestations were observed in each patient. MRI revealed multiple lesions. The majority of the lesions were located in the globus pallidus, sub cortical white matter, and basal ganglia. The cognitive injury, akinetic mutism, fecal and uroclepsia, forced crying, forced laughing and extra pyramidal syndromes such as chorea and parkinsonism were manifested in clinic. Cognitive impairment improved greatly while involuntary movements only improved slightly after several months. Meanwhile brain MRI suggested remarkable improvement. Neuroimaging directly correlated with the clinical manifestations.

Structural imaging in premanifest and manifest Huntington disease.

PubMed

Scahill, Rachael I; Andre, Ralph; Tabrizi, Sarah J; Aylward, Elizabeth H

2017-01-01

Huntington disease (HD) neuropathology has a devastating effect on brain structure and consequently brain function; neuroimaging provides a means to assess these effects in gene carriers. In this chapter we first outline the unique utility of structural imaging in understanding HD and discuss some of the acquisition and analysis techniques currently available. We review the existing literature to summarize what we know so far about structural brain changes across the spectrum of disease from premanifest through to manifest disease. We then consider how these neuroimaging findings relate to patient function and nonimaging biomarkers, and can be used to predict disease onset. Finally we review the utility of imaging measures for assessment of treatment efficacy in clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Mixed organic brain syndrome as a manifestation of systemic mastocytosis.

PubMed

Rogers, M P; Bloomingdale, K; Murawski, B J; Soter, N A; Reich, P; Austen, K F

1986-01-01

Systemic mastocytosis is a disease characterized by an excessive accumulation of mast cells, and associated with skin lesions, flushing, diarrhea, tachycardia, and psychiatric manifestations. In order to define more clearly the psychiatric manifestations, ten patients with this disorder underwent unstructured psychiatric interviews and a battery of psychologic testing. Both revealed a pattern of cognitive and affective changes in the majority of these patients, best categorized as an atypical or mixed organic brain syndrome. The cognitive changes consisted of diminished attention and memory, and the affective changes of anger, irritability, and, to a lesser extent, depression. These manifestations fluctuated with the level of disease activity, and appeared in some cases to respond to histamine antagonists and disodium cromoglycate, medications used to control the excessive mast cell activity. It is important for psychiatrists to be aware that mental status changes can represent psychiatric manifestations of mastocytosis, a readily treatable medical disorder.

Olmesartan-induced Enteropathy Manifesting as Wernicke-Korsakoff Syndrome.

PubMed

Uehara, Takanori; Ikusaka, Masatomi; Ohira, Yoshiyuki; Noda, Kazutaka; Suzuki, Shingo; Shikino, Kiyoshi; Kondo, Takeshi; Kajiwara, Hideki; Ikegami, Akiko; Hirota, Yusuke

Cases of sprue-like enteropathy associated with olmesartan have sporadically been encountered since it was first reported in 2012, and their most characteristic manifestation is severe diarrhea. We herein report the first case of sprue-like enteropathy manifesting as Wernicke-Korsakoff syndrome due to vitamin B1 malabsorption with only minimally increased bowel movements. When patients are receiving olmesartan and they complain of nonspecific chronic gastrointestinal symptoms, it is important to consider changing the drugs before any serious malabsorption syndrome develops.

Olmesartan-induced Enteropathy Manifesting as Wernicke-Korsakoff Syndrome

PubMed Central

Uehara, Takanori; Ikusaka, Masatomi; Ohira, Yoshiyuki; Noda, Kazutaka; Suzuki, Shingo; Shikino, Kiyoshi; Kondo, Takeshi; Kajiwara, Hideki; Ikegami, Akiko; Hirota, Yusuke

2016-01-01

Cases of sprue-like enteropathy associated with olmesartan have sporadically been encountered since it was first reported in 2012, and their most characteristic manifestation is severe diarrhea. We herein report the first case of sprue-like enteropathy manifesting as Wernicke-Korsakoff syndrome due to vitamin B1 malabsorption with only minimally increased bowel movements. When patients are receiving olmesartan and they complain of nonspecific chronic gastrointestinal symptoms, it is important to consider changing the drugs before any serious malabsorption syndrome develops. PMID:27980272

Musculoskeletal manifestations of Fabry disease: A retrospective study.

PubMed

Lidove, Olivier; Zeller, Valérie; Chicheportiche, Valérie; Meyssonnier, Vanina; Sené, Thomas; Godot, Sophie; Ziza, Jean-Marc

2016-07-01

Fabry disease is a rare X-linked metabolic disorder characterized by a deficiency in the enzyme alpha-galactosidase A. Both males and females can be affected. The main presenting symptom is pain in the extremities, whereas at a more advanced stage, the manifestations include hypertrophic cardiomyopathy, cardiac dysrhythmia, proteinuria, chronic kidney dysfunction, stroke, and hearing loss. When not diagnosed and treated, Fabry disease causes early death. No studies specifically designed to describe the musculoskeletal manifestations of Fabry disease are available. We conducted a single-center retrospective study of patients receiving follow-up at a Fabry disease referral center. We described the musculoskeletal manifestations and analyzed the differential diagnoses. Our study included 40 patients belonging to 20 families, including 25 females with a mean age of 44.2 years (range, 20-76 years) and 15 males with a mean age of 40.1 years (range, 16-61 years). Mean age at the diagnosis of Fabry disease was 37.2 years (range, 7-71 years) in the females and 26.9 years (range, 9-51 years) in the males. Specific enzyme replacement therapy was given to 10 (40%) females and 12 (80%) males. Musculoskeletal manifestations were as follows: past or present pain in the extremities (13 females and 10 males), combined in some patients with vasomotor disorders in the extremities and telangiectasia; exercise intolerance (12 females and 12 males); osteoporotic fractures (2 brothers aged 45 and 44 years, respectively); osteoporosis (3 females, aged 57, 63, and 75 years, respectively), which contributed to death in the oldest patient; osteopenia (2 females aged 38 and 47 years, respectively; and 1 male aged 43 years); Charcot foot and lymphedema with serious infectious complications (4 males older than 40 years), with avascular osteonecrosis of the lower limbs in 2 cases; toe amputations (3 cases); bilateral lower-limb amputation (1 case); abnormally slender lower limbs (5 females and

Ocular manifestations of rheumatoid arthritis and their correlation with anti-cyclic citrullinated peptide antibodies.

PubMed

Vignesh, Ammapati Paul Pandian; Srinivasan, Renuka

2015-01-01

To study the ocular manifestations of rheumatoid arthritis and to correlate the role of anti-cyclic citrullinated peptide antibody (anti-CCP antibody) with the ocular manifestations. Three-hundred and ninety-two eyes of the 196 rheumatoid arthritis patients who attended the ophthalmology outpatient department underwent a detailed ocular examination using slit lamp biomicroscopy and ophthalmoscopy. The tear function of all the patients was assessed using Schirmer's test, tear film break-up time and ocular surface staining. The anti-CCP antibody titers for all the rheumatoid arthritis patients were estimated using enzyme-linked immunosorbent assay tests. Seventy-seven patients (135 eyes, 39%) out of the 196 patients studied had ocular manifestations typical of rheumatoid arthritis. Dry eye was the most common manifestation (28%, 54 patients). Of the patients, 78% was females (60 patients). The mean duration of rheumatoid arthritis in patients with ocular manifestations was 5.4±2.7 years and without ocular manifestations was 2.1±1.6years. Three percent of the patients had episcleritis (six patients). Scleritis was present in 2% of the patients (four patients). Peripheral ulcerative keratitis and sclerosing keratitis was present in 1% of the population each (two patients each). Eighty-five percent (66 patients) had bilateral manifestations 15% (eleven patients) had unilateral manifestations. There was a strong association between the presence of anti-CCP antibodies and ocular manifestations of rheumatoid arthritis which was shown by the statistically significant P-value of <0.0001. Ocular manifestations are a significant part of the extra-articular manifestation of rheumatoid arthritis. Dry eye was the most common ocular manifestation. There was a statistically significant association between the presence of anti-CCP antibodies specific to rheumatoid arthritis and the ocular manifestations.

Tricyclic Compounds Containing Non-enolizable Cyano Enones. A Novel Class of Highly Potent Anti-inflammatory and Cytoprotective Agents=

PubMed Central

Honda, Tadashi; Yoshizawa, Hidenori; Sundararajan, Chitra; David, Emilie; Lajoie, Marc J.; Favaloro, Frank G.; Janosik, Tomasz; Su, Xiaobo; Honda, Yukiko; Roebuck, Bill D.; Gribble, Gordon W.

2011-01-01

Forty-four novel tricycles containing non-enolizable cyano enones (TCEs) were designed and synthesized on the basis of a semisynthetic pentacyclic triterpenoid, bardoxolone methyl, which is currently being developed in Phase II clinical trials for the treatment of severe chronic kidney disease in diabetic patients. Most of the TCEs having two different kinds of non-enolizable cyano enones in rings A and C are highly potent suppressors of induction of inducible nitric oxide synthase stimulated with interferon-γ, and highly potent inducers of the cytoprotective enzymes heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1. Among these compounds, (±)-(4bS,8aR,10aS)-10a-ethynyl-4b,8,8-trimethyl-3,7-dioxo-3,4b,7,8,8a,9,10,10a-octahydrophenanthrene-2,6-dicarbonitrile ((±)-31) is the most potent in these bioassays in our pool of drug candidates including semisynthetic triterpenoids and synthetic tricycles. These facts strongly suggest that an essential factor for potency is not a triterpenoid skeleton, but the cyano enone functionality. Notably, TCE 31 reduces hepatic tumorigenesis induced with aflatoxin in rats. Further preclinical studies and detailed mechanism studies on 31 are in progress. PMID:21361338

BRAF-mutated cells activate GCN2-mediated integrated stress response as a cytoprotective mechanism in response to vemurafenib.

PubMed

Nagasawa, Ikuko; Kunimasa, Kazuhiro; Tsukahara, Satomi; Tomida, Akihiro

2017-01-22

In BRAF-mutated melanoma cells, the BRAF inhibitor, vemurafenib, induces phosphorylation of eukaryotic initiation factor 2α (eIF2α) and subsequent induction of activating transcription factor 4 (ATF4), the central regulation node of the integrated stress response (ISR). While the ISR supports cellular adaptation to various stresses, the role of vemurafenib-triggered ISR has not been fully characterized. Here, we showed that in response to vemurafenib, BRAF-mutated melanoma and colorectal cancer cells rapidly induced the ISR as a cytoprotective mechanism through activation of general control nonderepressible 2 (GCN2), an eIF2α kinase sensing amino acid levels. The vemurafenib-triggered ISR, an event independent of downstream MEK inhibition, was specifically prevented by silencing GCN2, but not other eIF2α kinases, including protein kinase-like endoplasmic reticulum kinase, which transmits endoplasmic reticulum (ER) stress. Consistently, the ER stress gatekeeper, GRP78, was not induced by vemurafenib. Interestingly, ATF4 silencing by siRNA rendered BRAF-mutated melanoma cells sensitive to vemurafenib. Thus, the GCN2-mediated ISR can promote cellular adaptation to vemurafenib-induced stress, providing an insight into the development of drug resistance. Copyright © 2016 Elsevier Inc. All rights reserved.

77 FR 54863 - Polychlorinated Biphenyls (PCBs): Revisions to Manifesting Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-06

... and Recovery Act (RCRA) Uniform Hazardous Waste Manifest, under the Toxic Substances Control Act (TSCA... implement the Uniform Hazardous Waste Manifest form were promulgated on March, 4, 2005. DATES: Written... governmental jurisdiction that is a government of a city, county, town, school district or special district...

40 CFR 761.210 - Use of the manifest-Generator requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) TOXIC SUBSTANCES CONTROL ACT POLYCHLORINATED BIPHENYLS (PCBs) MANUFACTURING, PROCESSING, DISTRIBUTION IN COMMERCE, AND USE PROHIBITIONS PCB Waste Disposal Records and Reports § 761.210 Use of the manifest... remaining copies of the manifest. (c) For shipments of PCB waste within the United States solely by water...

40 CFR 761.210 - Use of the manifest-Generator requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) TOXIC SUBSTANCES CONTROL ACT POLYCHLORINATED BIPHENYLS (PCBs) MANUFACTURING, PROCESSING, DISTRIBUTION IN COMMERCE, AND USE PROHIBITIONS PCB Waste Disposal Records and Reports § 761.210 Use of the manifest... remaining copies of the manifest. (c) For shipments of PCB waste within the United States solely by water...

Red blood cells upregulate cytoprotective proteins and the labile iron pool in dividing human T cells despite a reduction in oxidative stress.

PubMed

Fonseca, Ana Mafalda; Pereira, Carlos F; Porto, Graça; Arosa, Fernando A

2003-12-01

We have recently reported that red blood cells (RBC) promote T cell growth and survival by inhibiting activation-induced T cell death. In the present study, we have examined parameters of oxidative stress and intracellular iron in activated T cells and correlated these data with the expression of ferritin, heme oxygenase-1 (HO-1), and the transferrin receptor CD71. T cells growing in the presence of RBC had reduced levels of reactive oxygen species (ROS) and oxidatively modified proteins, suggesting that RBC efficiently counteracted ROS production on the activated T cells. Flow cytometry and immunodetection demonstrated that T cells dividing in the presence of RBC had increased levels of intracellular ferritin rich in L-subunits and HO-1 along with a downmodulation in CD71 expression. Finally, using the fluorescent iron indicator calcein and flow cytometry analysis, we were able to show that a relative amount of the labile iron pool (LIP) was upregulated in T cells growing in the presence of RBC. These findings are consistent with a typical response to iron overload. However, neither heme compounds nor ferric iron reproduced the levels of expansion and survival of T cells induced by intact RBC. Altogether, these data suggest that RBC inhibit apoptosis of activated T cells by a combination of ROS scavenging and upregulation of cytoprotective proteins such as ferritin and HO-1, which may counteract a possible toxic effect of the increased intracellular free iron.

[Respiratory manifestations in aspergillosis].

PubMed

Regimbaud, M

1986-01-01

Aspergillus is a genus of cosmopolitan fungi with a selective pulmonary tropism. Their pathogenic role is due either to spreading in pre-existing pulmonary cavities, or to their allergizing capacity. Cavitary sequellae of tuberculosis and suppuration, particularly frequent and important in tropical environment, are elective localization for Aspergillus colonization. Surgical treatment is nowadays the only efficient one. Allergic manifestations are a more complex problem of therapy, exclusion of allergen being difficult to get in tropical environment.

Extra-articular manifestations of seronegative and seropositive rheumatoid arthritis.

PubMed

Sahatciu-Meka, Vjollca; Rexhepi, Sylejman; Manxhuka-Kerliu, Suzana; Rexhepi, Mjellma

2010-02-01

Although considered a "joint disease," rheumatoid arthritis is associated with the involvement of extra-articular manifestations. The aim of the study is the investigation and comparison of frequency and type of extra-articular manifestations in a well defined community based cohort of patients with seropositive and seronegative rheumatoid arthritis. Using the ACR (1987) criteria for rheumatoid arthritis, patients have been classified into the 2nd and 3rd functional class (ARA). The studied group consisted of 125 seronegative patients with titters lower than 1:64 as defined by Rose-Waaler test, whereas the control group consisted of 125 seropositive patients with titters of 1:64 or higher. All patients were between 25-60 years of age (Xb=49,96), with disease duration between 1-27 years (Xb=6,41). In order to present the findings of the study, the structure, prevalence, arithmetic mean (Xb), standard deviation (SB), variation quotient (QV%) and variation interval (Rmax-Rmin) have been used. Probability level has been expressed by p<0,01 and p<0,05. Correlation between the number of extra-articular manifestations and duration of the disease has been calculated by means of Pearson linear correlation. Higher presence of diffuse lung fibrosis, central and peripheral nervous system damages have been confirmed in the seropositive group, and osteoporosis in the seronegative; however, no statistical difference has been found. In extra-articular manifestations, "rheumatoid core" in the seropositive subset (chi2=4,80, p<0,05) presented significant statistical difference. Rheumatoid nodules were more frequent in seropositive subset (12%:16%), in both sexes; however, they were not of significant statistical difference. Neuropathy and lung diseases were also frequently present in seropositive group, but no statistical difference has been found regarding the statistical difference. Longer duration of the disease resulted in an increase of the number of extra

Herpes zoster vaccine effectiveness and manifestations of herpes zoster and associated pain by vaccination status.

PubMed

Marin, Mona; Yawn, Barbara P; Hales, Craig M; Wollan, Peter C; Bialek, Stephanie R; Zhang, John; Kurland, Marge J; Harpaz, Rafael

2015-01-01

Options for managing herpes zoster (HZ)-related pain and complications have limited effectiveness, making HZ prevention through vaccination an important strategy. Limited data are available on HZ vaccine effectiveness against confirmed HZ and manifestations of HZ among vaccinated persons. We conducted a matched case-control study to assess HZ vaccine effectiveness for prevention of HZ and other HZ-related outcomes and a cohort study of persons with HZ to compare HZ-related outcomes by vaccination status. Cases were identified through active surveillance among persons age ≥ 60 years with HZ onset and health-care encounters during 2010-2011 in Southeastern Minnesota. Controls were age- and sex-matched to cases. Data were collected by medical record review and from participants via interviews and daily pain diaries. 266 HZ case-patients and 362 matched controls were enrolled in the vaccine effectiveness studies and 303 case-patients in the cohort study of HZ characteristics by vaccination status. Vaccination was associated with 54% (95% CI:32%-69%) reduction in HZ incidence, 58% (95% CI:31%-75%) reduction in HZ prodromal symptoms, and 70% (95% CI:33%-87%) reduction in medically-attended prodrome. HZ vaccine was statistically significant effective at preventing postherpetic neuralgia (PHN) measured at 30 d after rash onset, 61% (95% CI: 22%-80%). Among persons who developed HZ, no differences were found by vaccination status in severity or duration of HZ pain after rash onset. In this population-based study, HZ vaccination was associated with >50% reduction in HZ, HZ prodrome, and medically-attended prodrome.

Herpes zoster vaccine effectiveness and manifestations of herpes zoster and associated pain by vaccination status

PubMed Central

Marin, Mona; Yawn, Barbara P; Hales, Craig M; Wollan, Peter C; Bialek, Stephanie R; Zhang, John; Kurland, Marge J; Harpaz, Rafael

2015-01-01

Options for managing herpes zoster (HZ)-related pain and complications have limited effectiveness, making HZ prevention through vaccination an important strategy. Limited data are available on HZ vaccine effectiveness against confirmed HZ and manifestations of HZ among vaccinated persons. We conducted a matched case-control study to assess HZ vaccine effectiveness for prevention of HZ and other HZ-related outcomes and a cohort study of persons with HZ to compare HZ-related outcomes by vaccination status. Cases were identified through active surveillance among persons age ≥60 years with HZ onset and health-care encounters during 2010-2011 in Southeastern Minnesota. Controls were age- and sex-matched to cases. Data were collected by medical record review and from participants via interviews and daily pain diaries. 266 HZ case-patients and 362 matched controls were enrolled in the vaccine effectiveness studies and 303 case-patients in the cohort study of HZ characteristics by vaccination status. Vaccination was associated with 54% (95% CI:32%-69%) reduction in HZ incidence, 58% (95% CI:31%-75%) reduction in HZ prodromal symptoms, and 70% (95% CI:33%-87%) reduction in medically-attended prodrome. HZ vaccine was statistically significant effective at preventing postherpetic neuralgia (PHN) measured at 30 d after rash onset, 61% (95% CI: 22%-80%). Among persons who developed HZ, no differences were found by vaccination status in severity or duration of HZ pain after rash onset. In this population-based study, HZ vaccination was associated with >50% reduction in HZ, HZ prodrome, and medically-attended prodrome. PMID:25806911

Cardiac tamponade as an initial manifestation of systemic lupus erythematosus.

PubMed

Carrion, Diego M; Carrion, Andres F

2012-06-12

Clinical manifestations of pericardial disease may precede other signs and symptoms associated with systemic lupus erythematosus. Although pericardial effusion is one of the most common cardiac problems in patients with systemic lupus erythematosus, haemodynamically significant effusions manifesting as cardiac tamponade are rare and require prompt diagnosis and treatment.

40 CFR 761.209 - Number of copies of a manifest.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., AND USE PROHIBITIONS PCB Waste Disposal Records and Reports § 761.209 Number of copies of a manifest... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Number of copies of a manifest. 761.209 Section 761.209 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC...

40 CFR 761.209 - Number of copies of a manifest.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., AND USE PROHIBITIONS PCB Waste Disposal Records and Reports § 761.209 Number of copies of a manifest... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Number of copies of a manifest. 761.209 Section 761.209 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC...

[Clinical manifestations of Legionella pneumonia in hematology patients].

PubMed

Galstian, G M; Kostina, I É; Katrysh, S A; Kliasova, G A; Karpova, T I; Tartakovskiĭ, I S

2014-01-01

To detect the most common clinical manifestations of Legionella pneumonia (LP) in immunocompromized patients. Clinical manifestations, the results of investigation of bronchoalveolar lavage fluid (BALF) and urine, and the data of lung computed tomography (CT) were studied in patients with blood system diseases and acute respiratory failure (ARF). The diagnosis of LP was verified in 8 (10.5%) of 76 patients with blood system diseases and ARF. The disease manifested as fever, higher concentrations of inflammatory markers (procalcitonin, fibrinogen), ARF, hypoxemia, and infiltrative lung injury. Six of the 8 patients were switched to mechanical ventilation. Lung CT showed no pathognomonic signs. Five of the 8 patients were observed to have renal dysfunction. The diagnosis of LP was made on the basis of the results of BALF examination in 7 patients and urinary antigen detection in 1. The disease was caused by Legionella pneumophila serogroup 1 in 3 patients and by L. pneumophila of other serogroups in the other patients. Therapy with respiratory fluoroquinolones was performed in 5 patients. Three patients died from progressive ARF and hypoxemia. BALF results were obtained after their death and therapy for legionellosis was not initiated. The incidence of LP is 10.5% in hematology patients. The clinical manifestations of legionellosis are nonspecific; its diagnosis requires bacteriological and/or serological evidence. Due to the high risk of death, it is reasonable to preuse respiratory fluoroquinolones or macrolides in immunocompromized patients with progressive ARF and suspected Legionella pneumonia before diagnosis.

Unusual Dermatological Manifestations of Gout: Review of Literature and a Case Report

PubMed Central

Ortega, Viviana Gómez; Gaona, Jennifer; Motta, Adriana; Medina Barragán, Oskar Javier

2015-01-01

Background: Gouty panniculitis is a rare clinical manifestation of gout, characterized by deposits of monosodium urate crystals in the hypodermis. Our aim was to describe atypical and rare clinical presentations of gouty tophi. Methods: We searched relevant English and Spanish literature of unusual gout manifestations using the following keywords: giant, gout, panniculitis, gouty panniculitis, gouty tophi, rare manifestations of gout, gouty, tophi, tophus, monosodium urate, uric acid, and unusual. Well-described case reports, case series, and review articles were evaluated and included in the literature review. Results: International literature has reported fewer than 10 cases of gouty panniculitis worldwide. In this case report, the patient presents a rare manifestation of gouty panniculitis, with typical joint injuries, gouty tophi in both lower and upper extremities, chronic gouty tophi in the nose, for which only 3 cases have been reported in literature, and great hypertrophy of adipose tissue in the lower back. Conclusions: Tophi can be found in atypical locations, which increase morbidities and deformities caused by the disease. We report an interesting case of gouty panniculitis associated with great hypertrophy of the adipose tissue, a rare manifestation of gout, and unusual locations of tophi. These clinical manifestations in our patient have not been recorded before, which leads us to think that we are in the presence of a new dermatological manifestation of gout. PMID:26301134

Ameliorative effects of pine bark extract on cisplatin-induced acute kidney injury in rats.

PubMed

Lee, In-Chul; Ko, Je-Won; Park, Sung-Hyeuk; Shin, Na-Rae; Shin, In-Sik; Kim, Yun-Bae; Kim, Jong-Choon

2017-11-01

This study investigated the dose-response effects of pine bark extract (PBE, pycnogenol ® ) on oxidative stress-mediated apoptotic changes induced by cisplatin (Csp) in rats. The ameliorating potential of PBE was evaluated after orally administering PBE at doses of 10 or 20 mg/kg for 10 days. Acute kidney injury was induced by a single intraperitoneal injection of Csp at 7 mg/kg on test day 5. Csp treatment caused acute kidney injury manifested by elevated levels of serum blood urea nitrogen (BUN) and creatinine (CRE) with corresponding histopathological changes, including degeneration of tubular epithelial cells, hyaline casts in the tubular lumen, and inflammatory cell infiltration (interstitial nephritis). Csp also induced significant apoptotic changes in renal tubular cells. In addition, Csp treatment induced high levels of oxidative stress, as evidenced by an increased level of malondialdehyde, depletion of the reduced glutathione (GSH) content, and decreased activities of glutathione S-transferase, superoxide dismutase, and catalase in kidney tissues. On the contrary, PBE treatment lowered BUN and CRE levels and effectively attenuated histopathological alterations and apoptotic changes induced by Csp. Additionally, treatment with PBE suppressed lipid peroxidation, prevented depletion of GSH, and enhanced activities of the antioxidant enzymes in kidney tissue. These results indicate that PBE has a cytoprotective effect against oxidative stress-mediated apoptotic changes caused by Csp in the rat kidney, which may be attributed to both increase of antioxidant enzyme activities and inhibition of lipid peroxidation.

Cardiac tamponade as an initial manifestation of systemic lupus erythematosus

PubMed Central

Carrion, Diego M; Carrion, Andres F

2012-01-01

Clinical manifestations of pericardial disease may precede other signs and symptoms associated with systemic lupus erythematosus. Although pericardial effusion is one of the most common cardiac problems in patients with systemic lupus erythematosus, haemodynamically significant effusions manifesting as cardiac tamponade are rare and require prompt diagnosis and treatment. PMID:22693326

Depressive Disorder, Anxiety Disorder and Chronic Pain: Multiple Manifestations of a Common Clinical and Pathophysiological Core.

PubMed

Arango-Dávila, Cesar A; Rincón-Hoyos, Hernán G

A high proportion of depressive disorders are accompanied by anxious manifestations, just as depression and anxiety often present with many painful manifestations, or conversely, painful manifestations cause or worsen depressive and anxious expressions. There is increasingly more evidence of the pathophysiological, and neurophysiological and technical imaging similarity of pain and depression. Narrative review of the pathophysiological and clinical aspects of depression and chronic pain comorbidity. Research articles are included that emphasise the most relevant elements related to understanding the pathophysiology of both manifestations. The pathological origin, physiology and clinical approach to these disorders have been more clearly established with the latest advances in biochemical and cellular techniques, as well as the advent of imaging technologies. This information is systematised with comprehensive images and clinical pictures. The recognition that the polymorphism of inflammation-related genes generates susceptibility to depressive manifestations and may modify the response to antidepressant treatments establishes that the inflammatory response is not only an aetiopathogenic component of pain, but also of stress and depression. Likewise, the similarity in approach with images corroborates not only the structural, but the functional and pathophysiological analogy between depression and chronic pain. Knowledge of depression-anxiety-chronic pain comorbidity is essential in the search for effective therapeutic interventions. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

40 CFR 265.72 - Manifest discrepancies.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 265.72 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL... waste solvent substituted for waste acid, or toxic constituents not reported on the manifest or shipping...

40 CFR 265.72 - Manifest discrepancies.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 265.72 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL... waste solvent substituted for waste acid, or toxic constituents not reported on the manifest or shipping...

40 CFR 265.72 - Manifest discrepancies.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 265.72 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL... waste solvent substituted for waste acid, or toxic constituents not reported on the manifest or shipping...

Hemophagocytic syndrome as the initial manifestation of systemic lupus erythematosus.

PubMed

Egües Dubuc, César Antonio; Uriarte Ecenarro, Miren; Meneses Villalba, Carlos; Aldasoro Cáceres, Vicente; Hernando Rubio, Iñaki; Belzunegui Otano, Joaquín

2014-01-01

Hemophagocytic syndrome (HS) occurs in autoimmune diseases and belongs to the hemophagocytic lymphohistiocytosis group of diseases. This paper describes the features of 2 patients with systemic lupus erythematosus (SLE) who presented HS as the initial clinical manifestation. Both patients had prolonged fever not associated to an infectious process and did not respond to broad-spectrum antibiotics. The diagnosis of HS secondary to SLE is complicated, because it has some features in common, but HS is characterized by hyperferritinemia, hipofibrinogemia, hypertriglyceridemia and a decrease in the erythrocyte sedimentation rate, unlike SLE. HS treatment when associated to SLE is not well established, but steroids and/or immunoglobulins are effective as the initial treatment, and in refractory cases, cyclosporine or cyclophosphamide may be associated. HS can be the initial manifestation of SLE and should be suspected in patients with organ enlargement, cytopenias, clotting disorders, liver disorders and prolonged fever unresponsive to antibiotics. Anakinra may be a treatment option in adult HS associated to SLE. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Oral manifestations of HIV/AIDS in Asia: Systematic review and future research guidelines.

PubMed

Sharma, Gaurav; Oberoi, Sukhvinder-Singh; Vohra, Puneeta; Nagpal, Archna

2015-07-01

The authors have conducted a systematic review of oral manifestations of HIV from studies conducted in Asia to establish the characteristics and prevalence of individual oral manifestations in Asia, and to assess the direction of future research studies on oral manifestations of HIV in Asia. The electronic retrieval systems and databases searched for relevant articles were PubMed [MEDLINE], EBSCO, and EMBASE. The search was for limited articles published in English or with an English abstract and articles published during the period January 1995 to August 2014. The authors reached a final overall sample of 39 studies that were conducted in Asia. The median population size among all studies was 312.7 patients. Oral candidiasis [OC] was the most common oral manifestation [37.7%] in studies conducted in Asia. The overall prevalence of oral hairy leukoplakia and melanotic hyperpigmentation was computed to be 10.1% and 22.8% respectively. Thailand and India are primarily countries with maximum research on oral manifestations. The research on oral manifestations of HIV in Asia has to upgrade to more interventional and therapeutic studies rather than the contemporary cross- sectional epidemiological descriptive studies. The authors have given suggestions and future directions for the implementation of clinical research of oral manifestations in HIV patients. Key words:Oral manifestations, HIV/AIDS, Asia, Systematic review.

Tuberous sclerosis complex: Recent advances in manifestations and therapy.

PubMed

Wataya-Kaneda, Mari; Uemura, Motohide; Fujita, Kazutoshi; Hirata, Haruhiko; Osuga, Keigo; Kagitani-Shimono, Kuriko; Nonomura, Norio

2017-09-01

Tuberous sclerosis complex is an autosomal dominant inherited disorder characterized by generalized involvement and variable manifestations with a birth incidence of 1:6000. In a quarter of a century, significant progress in tuberous sclerosis complex has been made. Two responsible genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively, were discovered in the 1990s, and their functions were elucidated in the 2000s. Hamartin-Tuberin complex is involved in the phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin signal transduction pathway, and suppresses mammalian target of rapamycin complex 1 activity, which is a center for various functions. Constitutive activation of mammalian target of rapamycin complex 1 causes variable manifestations in tuberous sclerosis complex. Recently, genetic tests were launched to diagnose tuberous sclerosis complex, and mammalian target of rapamycin complex 1 inhibitors are being used to treat tuberous sclerosis complex patients. As a result of these advances, new diagnostic criteria have been established and an indispensable new treatment method; that is, "a cross-sectional medical examination system," a system to involve many experts for tuberous sclerosis complex diagnosis and treatments, was also created. Simultaneously, the frequency of genetic tests and advances in diagnostic technology have resulted in new views on symptoms. The numbers of tuberous sclerosis complex patients without neural symptoms are increasing, and for these patients, renal manifestations and pulmonary lymphangioleiomyomatosis have become important manifestations. New concepts of tuberous sclerosis complex-associated neuropsychiatric disorders or perivascular epithelioid cell tumors are being created. The present review contains a summary of recent advances, significant manifestations and therapy in tuberous sclerosis complex. © 2017 The Japanese Urological Association.

The Heart of the Matter: Cardiac Manifestations of Endocrine Disease

PubMed Central

Binu, Aditya John; Cherian, Kripa Elizabeth; Kapoor, Nitin; Chacko, Sujith Thomas; George, Oommen; Paul, Thomas Vizhalil

2017-01-01

Endocrine disorders manifest as a disturbance in the milieu of multiple organ systems. The cardiovascular system may be directly affected or alter its function to maintain the state of homeostasis. In this article, we aim to review the pathophysiology, diagnosis, clinical features and management of cardiac manifestations of various endocrine disorders. PMID:29285459

Hepatic angiosarcoma manifested as recurrent hemoperitoneum

PubMed Central

Lee, Seung-Woo; Song, Chun-Young; Gi, Young-Hwa; Kang, Sang-Beom; Kim, Yon-Soo; Nam, Soon-Woo; Lee, Dong-Soo; Kim, Jong-Ok

2008-01-01

Angiosarcoma is a rare tumor that account for less than 1% of all sarcomas. Although hepatic angiosarcoma usually presents with unspecific symptoms, it rapidly progresses and has a high mortality. We report a rare case of primary hepatic angiosarcoma manifested as recurrent hemoperitoneum. PMID:18473427

40 CFR 761.208 - Obtaining manifests.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PROHIBITIONS PCB Waste Disposal Records and Reports § 761.208 Obtaining manifests. (a)(1) A generator may use... 761.208 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL...) Commercial printer; (iii) PCB waste generator, transporter or, designated facility; or (iv) PCB waste broker...

40 CFR 761.208 - Obtaining manifests.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROHIBITIONS PCB Waste Disposal Records and Reports § 761.208 Obtaining manifests. (a)(1) A generator may use... 761.208 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL...) Commercial printer; (iii) PCB waste generator, transporter or, designated facility; or (iv) PCB waste broker...

Orbital manifestations in patients with acquired immunodeficiency syndrome.

PubMed

Sodhi, Punita Kumari

2014-01-01

The orbital manifestations of acquired immunodeficiency syndrome(AIDS) are uncommon. To provide a review of orbital manifestations of AIDS, the predisposing factors, investigations, treatment and outcome. Meticulous and systematic literature search of Pubmed to identify manuscripts describing orbital manifestations of AIDS was done and the articles were reviewed.The keywords used in the search were “orbit and AIDS”, “HIV positive and orbit”,“orbit manifestations in AIDS”, “orbital disease and AIDS” and “orbital infections and AIDS”. The orbital involvement in AIDS may present with opportunistic infections from organisms like fungi, viruses, bacteria and protozoa or with malignancies like Kaposi’s sarcoma, squamous cell carcinoma, smooth muscle cell tumors and lymphoma.The predisposing factors for orbital involvement in AIDS are low CD4+ cell count and the immunosuppressive states like diabetes, diabetic ketoacidosis, intravenous drug abuse and neutropenia. A patient may present with fever, headache, nausea, vomiting,decreased vision, ocular pain, and, in cases of mass formation, there is periorbital swelling, axial proptosis, globe displacement and swollen optic disc. Radiologically,mass formation, orbital bony destruction, and spread of disease to contiguous structures including the central nervous system may be seen. The medical management includes therapy for infection and HIV-1 protease inhibitors (highly active antiretroviral therapy)to suppress HIV-1 replication. For tumors, radical surgery including debulking followed by postoperative radiotherapy is generally needed. Orbital involvements with AIDS in any form, infective or malignancy, causes significant morbidity and mortality and should be diagnosed and managed as early as possible.

[Spanish adaptation of the Stress Manifestations Scale of the Student Stress Inventory (SSI-SM)].

PubMed

Escobar Espejo, Milagros; Blanca, María J; Fernández-Baena, F Javier; Trianes Torres, María Victoria

2011-08-01

The aim of the present study was to translate into Spanish and to describe the psychometric properties of the Stress Manifestations Scale of the Student Stress Inventory (SSI-SM), developed by Fimian, Fastenau, Tashner and Cross to identify the main manifestations of stress in adolescents. The scale was applied to a sample of 1,002 pupils from years one and two of Secondary Education. The paper reports the factor structure, an item analysis, the internal consistency, differences by sex and academic year, external evidence of validity, and norms for scoring the scale. The results reveal a factor structure based on three first-order factors (emotional manifestations, physiological manifestations and behavioural manifestations) and one second-order factor (indicative of stress manifestations). In terms of external validity, there was a positive association with measures of perceived stress, aggressiveness, internalized/externalized symptoms, and a negative association with life satisfaction. The results show that the scale is an adequate tool for evaluating stress manifestations in adolescents.

Atypical Manifestations of Hyperthyroidism

PubMed Central

Boxall, E. A.; Lauener, R. W.; McIntosh, H. W.

1964-01-01

Patients with hyperthyroidism usually present with symptoms of hypermetabolism with or without goitre and/or eye signs. Occasionally, however, the chief complaints are not immediately suggestive of hyperthyroidism. Patients with hyperthyroidism are described who presented with such atypical manifestations as periodic muscular paralysis, myasthenia, myopathy, encephalopathy, psychosis, angina pectoris, atrial fibrillation, heart failure without underlying heart disease, skeletal demineralization, pretibial myxedema, unilateral eye signs, and pitting edema of the ankles. ImagesFig. 2Fig. 3Fig. 5Fig. 7Fig. 8Fig. 9Fig. 10 PMID:14178405

A Review of the Latent and Manifest Benefits (LAMB) Scale

ERIC Educational Resources Information Center

Muller, Juanita; Waters, Lea

2012-01-01

The latent and manifest benefits (LAMB) scale (Muller, Creed, Waters & Machin, 2005) was designed to measure the latent and manifest benefits of employment and provide a single scale to test Jahoda's (1981) and Fryer's (1986) theories of unemployment. Since its publication in 2005 there have been 13 studies that have used the scale with 5692…

Tamarix gallica phenolics protect IEC-6 cells against H2O2 induced stress by restricting oxidative injuries and MAPKs signaling pathways.

PubMed

Bettaib, Jamila; Talarmin, Hélène; Droguet, Mickaël; Magné, Christian; Boulaaba, Mondher; Giroux-Metges, Marie-Agnès; Ksouri, Riadh

2017-05-01

Polyphenolic compounds gained interest in the pharmaceutical research area due to their beneficial properties. Herein, antioxidant and cytoprotective capacities of T. gallica extract on H 2 O 2 -challenged rat small intestine epithelial cells were investigated. To set stress conditions, IEC-6 cultures were challenged with numerous H 2 O 2 doses and durations. Then, 40μM H 2 O 2 during 4h were selected to assess the cytoprotective effect of different T. gallica extract concentrations. Oxidative parameters, measured through CAT and SOD activities as well as MDA quantification were assessed. In addition, the expression of possibly involved MAPKs was also valued. Main results reported that T. gallica was rich in polyphenols and exhibited an important antioxidant activity (DPPH Assay, IC 50 =6μgmL -1 ; ABTS + test, IC 50 =50μgmL -1 ; Fe-reducing power, EC 50 =100μgmL -1 ). The exposure of IEC-6 cultures to 40μM H 2 O 2 during 4h caused oxidative stress manifested by (i) over 70% cell mortality, (ii) over-activity of CAT (246%), (iii) excess in MDA content (18.4nmolmg -1 ) and (iiii) a trigger of JNK phosphorylation. Pretreatment with T. gallica extract, especially when used at 0.25μgmL -1 , restored cell viability to 122%, and normal cell morphology in H 2 O 2 -chalenged cells. In addition, this extract normalized CAT activity and MDA content (100% and 14.7nmolmg -1 , respectively) to their basal levels as compared to control cells. Furthermore, stopping cell death seems to be due to dephosphorylated JNK MAPK exerted by T. gallica bioactive compounds. In all, T. gallica components provided a cross-talk between regulatory pathways leading to an efficient cytoprotection against harmful oxidative stimulus. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

19 CFR 122.75 - Complete manifest.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Complete manifest. 122.75 Section 122.75 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Documents Required for Clearance and Permission To Depart; Electronic...

Dietary Fish Oil Blocks the Microcirculatory Manifestations of Ischemia- Reperfusion Injury in Striated Muscle in Hamsters

NASA Astrophysics Data System (ADS)

Lehr, Hans-Anton; Hubner, Christoph; Nolte, Dirk; Kohlschutter, Alfried; Messmer, Konrad

1991-08-01

Epidemiologic observations and experimental studies have demonstrated a protective effect of dietary fish oil on the clinical manifestations of ischemia-reperfusion injury. To investigate the underlying mechanisms, we used the dorsal skinfold chamber model for intravital fluorescence microscopy of the microcirculation in striated muscle of awake hamsters. In control hamsters (n = 7), reperfusion after a 4-hr pressure-induced ischemia to the muscle tissue elicited the adhesion of fluorescently stained leukocytes to the endothelium of postcapillary venules, capillary obstruction, and the breakdown of endothelial integrity. These microvascular manifestations of ischemia-reperfusion injury were significantly attenuated in animals (n = 7) when fed with a fish oil-enriched diet for 4 weeks prior to the experiments. In leukocyte total lipids, the fish oil diet resulted in a substantial displacement of arachidonic acid, the precursor of the potent adhesionpromoting leukotriene (LT) B_4, by fish oil-derived eicosapentaenoic acid, the precursor of biologically less potent LTB_5, emphasizing the mediator role of LTB_4 in ischemia-reperfusion injury. These results suggest that the preservation of microvascular perfusion by dietary fish oil contributes to its protective effects on the clinical manifestations of ischemia-reperfusion injury.

[Digestive system manifestations in children infected with novel influenza A (H1N1) virus].

PubMed

Wei, Ju-Rong; Lu, Zhi-Wei; Tang, Zheng-Zhen; Wang, He-Ping; Zheng, Yue-Jie

2010-10-01

To study the digestive system manifestations in children infected with novel influenza A (H1N1) virus. A prospective study of 153 children infected with novel influenza A (H1N1) virus in Shenzhen Children's Hospital from November 2009 to January 2010 was conducted. The clinical features and outcomes of 69 children with digestive system manifestations were analyzed. The children presenting with digestive system manifestations accounted for 45% (69 cases) in the 153 hospitalized children with novel influenza A (H1N1) infection. Gastrointestinal manifestations were observed in 50 cases (33%) and liver function abnormality in 19 cases (12%). The incidence rate of coma, neurological complications, increase in creative kinase level, ICU admission, and death in the patients with digestive system manifestations were significantly higher than those without digestive system manifestations (P<0.05). In the 69 patients with digestive system manifestations, 5 died from severe complications and 64 recovered fully. Gastrointestinal manifestations disappeared through 1 to 3 days and abnormal liver function recovered through 4 to 7 days. Digestive system manifestations are common in children infected with novel influenza A (H1N1) virus. Neurological system involvements are more common in the patients with digestive system manifestations than those without.

[Cardiac sarcoidosis - clinical manifestation and diagnosis].

PubMed

Błaut-Jurkowska, Justyna; Podolec, Piotr; Olszowska, Maria

2016-08-01

Sarcoidosis is a multisystem inflammatory disease defined histologically by the formation of noncaseating granulomas. The etiology of sarcoidosis remains unknown. Heart involvement in the course of sarcoidosis concerns about 5% of patients. The most common manifestation of cardiac sarcoidosis are conduction abnormalities, arrhythmias and heart failure. The diagnostic algorithm includes performing a clinical history, a 12-lead electrocardiogram (ECG) and an echocardiogram. If any of the initial screening investigations yields an abnormality, diagnostics should be continue using advanced imaging techniques: cardiovascular magnetic resonance (CMR) or fluorodeoxyglucose positron emission tomography (FDG-PET). Nowadays endomyocardial biopsy is not performed routinely.The clinical picture of cardiac sarcoidosis is highly variable. Screening for cardiac sarcoidosis should be performed in all patients diagnosed with extracardiac sarcoidosis. Cardiac sarcoidosis should also be suspected in young patients without a diagnosis of sarcoidosis who present with conduction abnormalities of unknown etiology, because cardiac sarcoidosis may be the first or the only manifestation of the disease. © 2016 MEDPRESS.

Clinical manifestations and diagnosis of acromegaly.

PubMed

Lugo, Gloria; Pena, Lara; Cordido, Fernando

2012-01-01

Acromegaly and gigantism are due to excess GH production, usually as a result of a pituitary adenoma. The incidence of acromegaly is 5 cases per million per year and the prevalence is 60 cases per million. Clinical manifestations in each patient depend on the levels of GH and IGF-I, age, tumor size, and the delay in diagnosis. Manifestations of acromegaly are varied and include acral and soft tissue overgrowth, joint pain, diabetes mellitus, hypertension, and heart and respiratory failure. Acromegaly is a disabling disease that is associated with increased morbidity and reduced life expectancy. The diagnosis is based primarily on clinical features and confirmed by measuring GH levels after oral glucose loading and the estimation of IGF-I. It has been suggested that the rate of mortality in patients with acromegaly is correlated with the degree of control of GH. Adequately treated, the relative mortality risk can be markedly reduced towards normal.

Clinical Manifestations and Diagnosis of Acromegaly

PubMed Central

Lugo, Gloria; Pena, Lara; Cordido, Fernando

2012-01-01

Acromegaly and gigantism are due to excess GH production, usually as a result of a pituitary adenoma. The incidence of acromegaly is 5 cases per million per year and the prevalence is 60 cases per million. Clinical manifestations in each patient depend on the levels of GH and IGF-I, age, tumor size, and the delay in diagnosis. Manifestations of acromegaly are varied and include acral and soft tissue overgrowth, joint pain, diabetes mellitus, hypertension, and heart and respiratory failure. Acromegaly is a disabling disease that is associated with increased morbidity and reduced life expectancy. The diagnosis is based primarily on clinical features and confirmed by measuring GH levels after oral glucose loading and the estimation of IGF-I. It has been suggested that the rate of mortality in patients with acromegaly is correlated with the degree of control of GH. Adequately treated, the relative mortality risk can be markedly reduced towards normal. PMID:22518126

Continuous de novo biosynthesis of haem and its rapid turnover to bilirubin are necessary for cytoprotection against cell damage

PubMed Central

Takeda, Taka-aki; Mu, Anfeng; Tai, Tran Tien; Kitajima, Sakihito; Taketani, Shigeru

2015-01-01

It is well known that haem serves as the prosthetic group of various haemoproteins that function in oxygen transport, respiratory chain, and drug metabolism. However, much less is known about the functions of the catabolites of haem in mammalian cells. Haem is enzymatically degraded to iron, carbon monoxide (CO), and biliverdin, which is then converted to bilirubin. Owing to difficulties in measuring bilirubin, however, the generation and transport of this end product remain unclear despite its clinical importance. Here, we used UnaG, the recently identified bilirubin-binding fluorescent protein, to analyse bilirubin production in a variety of human cell lines. We detected a significant amount of bilirubin with many non-blood cell types, which was sensitive to inhibitors of haem metabolism. These results suggest that there is a basal level of haem synthesis and its conversion into bilirubin. Remarkably, substantial changes were observed in the bilirubin generation when cells were exposed to stress insults. Since the stress-induced cell damage was exacerbated by the pharmacological blockade of haem metabolism but was ameliorated by the addition of biliverdin and bilirubin, it is likely that the de novo synthesis of haem and subsequent conversion to bilirubin play indispensable cytoprotective roles against cell damage. PMID:25990790

Protective effects of Lagerstroemia speciosa on 3-morpholinosydnonimine (SIN-1)-induced oxidative stress in HIT-T15 pancreatic β cells.

PubMed

Song, Jia-Le; Zhao, Xin; Wang, Qiang; Zhang, Ting

2013-05-01

Reactive oxygen species (ROS)-induced pancreatic β cell death affects insulin secretion and is important in the pathogenesis of diabetes. Lagerstroemia speciosa, a traditional folk medicine, has been used for t he prevention and treatment of diabetes. However, whether Lagerstroemia speciosa has a cytoprotective effect on pancreatic β cells remains to be elucidated. The present study aimed to investigate the cytoprotective effects of hot water extracts from Lagerstroemia speciosa leaves (LWE) on 3-morpholinosydnonimine (SIN-1)-induced oxidative damage in Syrian hamster pancreatic insulinoma HIT-T15 cells. The HIT-T15 cells were first treated with SIN-1 (50 µM) for 24 h and then co-incubated with LWE for 48 h. SIN-1 significantly decreased HIT-T15 cell viability (P<0.05); however, LWE did not exert a significant cytotoxic effect and increased the viability of HIT-T15 cells in a dose‑dependent manner. To further investigate the protective effects of LWE on SIN-1‑induced oxidative stress in HIT-T15 cells, the cellular levels of ROS, lipid peroxidation and endogenous antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-px), were determined. LWE decreased the intracellular levels of ROS and lipid peroxidation, and increased the activities of antioxidant enzymes. These results suggest that LWE has a cytoprotective effect against SIN-1‑induced oxidative stress in HIT-T15 cells through the inhibition of lipid peroxidation, a decrease in ROS levels and an increase in antioxidant enzyme activity. In addition, LWE increased insulin secretion in SIN-1-treated HIT-T15 cells. Our results suggested that LWE were effective in the treatment of diabetes. Further studies are required to study the anti-diabetic molecular mechanism in a cell model.

Space Launch System Co-Manifested Payload Options for Habitation

NASA Technical Reports Server (NTRS)

Smitherman, David

2015-01-01

The Space Launch System (SLS) has a co-manifested payload capability that will grow over time as the launch vehicle matures and planned upgrades are implemented. The final configuration is planned to be capable of inserting a payload greater than 10 metric tons (mt) into a trans-lunar injection trajectory along with the crew in the Orion capsule and its service module. The co-manifested payload is located below the Orion and its service module in a 10 m high fairing similar to the way the Saturn launch vehicle carried the lunar lander below the Apollo command and service modules. Various approaches that utilize this comanifested payload capability to build up infrastructure in deep space have been explored in support of future asteroid, lunar, and Mars mission scenarios. This paper reports on the findings of the Advanced Concepts Office study team at NASA Marshall Space Flight Center (MSFC) working with the Advanced Exploration Systems Program on the Exploration Augmentation Module Project. It includes some of the possible options for habitation in the co-manifested payload volume of the SLS. Findings include a set of module designs that can be developed in 10 mt increments to support these co-manifested payload missions along with a comparison of this approach to a large-module payload flight configuration for the SLS.

Osteo-articular manifestations of amyloidosis.

PubMed

M'bappé, Pauline; Grateau, Gilles

2012-08-01

Whether it is overload disease or mispleated proteins, amyloid is a great pretender. This is especially true for all of the osteo-articular manifestations of amyloid light chain (AL) amyloidosis, which may mimic rheumatoid arthritis, polymyalgia rheumatica, a myeloma or a bone tumour. To improve the prognosis, AL amyloidosis must be considered in front of atypical osteo-articular manifestations. Amyloidosis Ab2M of chronic haemodialysis (members' arthropathy and destructive spondylitis) is a specific entity that needs to be differentiated from other osteoarthropathies of chronic renal failure. It has become exceptional since the progress of haemodialysis. Finally transthyretin amyloidosis(ATTR) can be responsible for carpal tunnel syndrome(CTS) in its genetic and senile form. Although amyloidosis is rare, it represents one of the aetiologies of CSC, regardless of its type. In the specific context of haemodialysis, this poses no difficulty for the clinician. Yet AL amyloidosis must be considered more often, as must senile amyloidosis ATTR in the elderly. It seems obvious that the anatomo-pathologic analysis with specific staining with Congo red - see typing - should be systematically performed in the case of surgical neurolysis. Amyloidosis is defined by the extracellular deposit of proteins which share common tinctorial affinities, a fibril aspect under electron microscopy and spatial conformation called beta pleated. Once regarded as a mere overload disease, it is currently considered as a disease of misfolded proteins. Indeed, it is certain that abnormalities of spatial pattern play an essential role in the responsibility for the pathology of many proteins whose amyloid fibre is the final common way. They involve both changes in the conformation of proteins and other major in vivo interactions between amyloid protein and the extracellular matrix. In most cases, amyloidosis represents the bulk of histopathological lesions and its pathogenic role is certain. In

Otorhinolaryngology manifestations secondary to oral sex.

PubMed

Fernández-López, Claudia; Morales-Angulo, Carmelo

Over the last few years, oral and pharyngeal signs and symptoms due to oral sex have increased significantly. However, no review articles related to this subject have been found in the medical literature. The objective of our study was to identify otorhinolaryngological manifestations associated with orogenital/oroanal contact, both in adults and children, in the context of consensual sex or sexual abuse. We performed a review of the medical literature on otorhinolaryngological pathology associated with oral sex published in the last 20 years in the PubMed database. Otorhinolaryngological manifestations secondary to oral sex practice in adults can be infectious, tumoral or secondary to trauma. The more common signs and symptoms found in the literature were human papillomavirus infection (above all, condyloma acuminata and papilloma/condyloma), oral or pharyngeal syphilis, gonococcal pharyngitis, herpes simplex virus infection and pharyngitis from Chlamydia trachomatis. The incidence of human papillomavirus -induced oropharyngeal carcinoma has dramatically increased. In children past the neonatal period, the presence of condyloma acuminatus, syphilis, gonorrhoea or palatal ecchymosis (the last one, unless justified by other causes) should make us suspect sexual abuse. Sexual habits have changed in the last decades, resulting in the appearance of otorhinolaryngological pathology that was rarely seen previously. For this reason, it is important for primary care physicians to have knowledge about the subject to perform correct diagnosis and posterior treatment. Some sexual abuse cases in children may also be suspected based on the knowledge of the characteristic oropharyngeal manifestations secondary to them. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

Oral manifestations in Kindler syndrome: case report and discussion of literature findings.

PubMed

Barbosa, Nathalia Mocellin; Visioli, Fernanda; Martins, Manoela Domingues; Martins, Marco Antônio Trevizani; Munerato, Maria Cristina

2016-07-01

Kindler syndrome is a rare genetic disorder showing some predominant clinical manifestations, for example, trauma-induced blisters, progressive poikiloderma, skin atrophy, and photosensitivity. Oral manifestations are not commonly described and can be often misdiagnosed. This report describes the case of a female patient diagnosed with Kindler syndrome showing the classical clinical features affecting the skin, in addition to oral lesions manifesting as keratotic plaques and ulcers affecting the buccal mucosa, floor of the mouth, alveolar ridge, hard palate, and soft palate. An incisional biopsy was performed to confirm the diagnostic hypothesis of an autoimmune lesion possibly related with the syndrome. Knowledge about the possible manifestations of the Kindler syndrome is important to improve its management. © 2016 Special Care Dentistry Association and Wiley Periodicals, Inc.

Enterovirus infections in Singaporean children: an assessment of neurological manifestations and clinical outcomes.

PubMed

Thong, Wen Yi; Han, Audrey; Wang, S J Furene; Lin, Jeremy; Isa, Mas Suhaila; Koay, Evelyn Siew Chuan; Tay, Stacey Kiat-Hong

2017-04-01

Enterovirus infections in childhood can be associated with significant neurological morbidity. This study aimed to describe the prevalence and range of neurological manifestations, determine the clinical characteristics and assess differences in clinical outcomes for Singaporean children diagnosed with enterovirus infections. In this single-centre, case-control study, clinical data was collected retrospectively from patients admitted to National University Hospital, Singapore, from August 2007 to October 2011 and diagnosed with enterovirus infection, based on the enterovirus polymerase chain reaction test, or cultures from throat and rectal swabs or cerebrospinal fluid samples. The occurrence of neurological manifestations was reviewed and clinical outcomes were assessed. A total of 48 patients (age range: six days-17.8 years) were included in the study. Neurological manifestations were seen in 75.0% of patients, 63.9% of whom presented with aseptic meningitis. Other neurological manifestations included encephalitis, acute cerebellitis, transverse myelitis and autonomic dysfunction. The incidence of neurological manifestations was significantly higher in patients aged > 1 year as compared to younger patients (p = 0.043). In patients without neurological manifestations, a significantly higher proportion presented with hand, foot and mouth disease and poor feeding. Long-term neurological sequelae were seen in 16.7% of patients with neurological manifestations. A wide spectrum of neurological manifestations resulting in a relatively low incidence of long-term neurological sequelae was observed in our study of Singaporean children with enterovirus infections. As some of these neurological morbidities were severe, careful evaluation of children with neurological involvement is therefore necessary. Copyright: © Singapore Medical Association

77 FR 6135 - Agency Information Collection Activities: Cargo Manifest/Declaration, Stow Plan, Container Status...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-07

... Activities: Cargo Manifest/ Declaration, Stow Plan, Container Status Messages and Importer Security Filing... the Paperwork Reduction Act: Cargo Manifest/Declaration, Stow Plan, Container Status Messages and..., mechanical, or other technological techniques or other forms of information. Title: Cargo Manifest...

[Rare ocular manifestation with suspect alport syndrome].

PubMed

Krejčířová, I; Varadyová, B; Doležel, Z; Autrata, R; Matúšová, J; Gregorová, E

2014-06-01

The authors mention a case report of a 13 year old girl with renal disease, who visited the outpatient Department of Pediatric Ophthalmology, University Hospital Brno with subjective complaints on decreased vision of both eyes. Ophthalmologic examination showed physiological foveolar reflex on fundus and very discrete changes of the retinal pigment epithelium in macula, the fundus periphery was without pathology. OCT images showed bilateral atrophy of central macula and changes at the level of the photoreceptors. The authors describe a rare ocular manifestation of macular atrophy with suspect Alport syndrome, which strengthened the suspicion of this disease. The authors also mention other possible ocular manifestations of Alport syndrome and compare the findings with the up to date international references. Key words: Alport syndrome, X heterozygot Alport syndrome, macular atrophy, lentikonus.

Violent and criminal manifestations in dementia patients.

PubMed

Cipriani, Gabriele; Lucetti, Claudio; Danti, Sabrina; Carlesi, Cecilia; Nuti, Angelo

2016-05-01

Although the older adults have been studied as victims of violence, geriatric patients can display violent behavior. The purpose of the present review was to explore the phenomenon of criminal violations and violent acts in people with dementia. The authors used PubMed to search the MEDLINE database and other sources for original research and review articles on criminal and violent manifestation in demented patients combining the terms "criminal manifestation," "violence, aggressive behavior," "homicide," "suicide" and "homicide-suicide" together with "dementia". Possible biomarkers of violence are considered. The present review highlights the risk factors for violence in patients suffering from dementia, and reviews the literature about criminal violations and homicidal/suicidal behavior in this patient group. Geriatr Gerontol Int 2016; 16: 541-549. © 2015 Japan Geriatrics Society.

Zika Virus: Cutaneous Manifestations in 3 Patients.

PubMed

Cosano-Quero, A; Velasco-Tirado, V; Sánchez Seco, M P; Manzanedo-Bueno, L; Belhassen-García, M

2018-04-01

Zika virus infection should be suspected in travelers or immigrants with the signs or symptoms of a viral infection (rash, fever, joint pains, conjunctivitis, headache, etc.) and a compatible epidemiological history. Although cutaneous manifestations are among the most common clinical signs of Zika, they are not specific and very few images are available. We present 3 patients (2 travelers and 1 immigrant) in whom a rash was the presenting manifestation of Zika virus infection. Prompt diagnosis optimizes outcomes in these patients, improves the management of severe disease, and minimizes the risk of local transmission by Aedes albopictus, now a potential local vector for the virus due to its presence in areas along Spain's Mediterranean coast. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Different manifestation of depressive disorder in the elderly.

PubMed

Shahpesandy, Homayun

2005-12-01

To compare the clinical manifestation of depressive disorder in elderly, and younger adults. To compare the clinical manifestation of depressive disorder, we evaluate 46 elderly (33 female, and 13 male, mean age 71.1) and 60 younger adults (40 female, and 20 male, mean age 44.5 years). All patients suffering from depressive disorders according to ICD-10. For evaluation and comparison of depressive symptomatology we used the HAM-D-17. The results analysed by the SPSS. The clinical manifestation of depression is different in the elderly. Elderly depressed patients compared with their younger counterparts, scored significantly less in Depressed mood, but significantly higher in Work and activities, Retardation, Somatic symptoms-general, Hypochondriasis, Insomnia-middle, Insomnia-late, Anxiety-somatic, and Somatic symptoms-gastrointestinal. On the other hand, younger patients scored significantly higher in Feelings of guilt, and Genital symptoms. Clinical presentation of depressive disorder is different in the elderly, depressed mood is often absent or masked. Anxiety, somatization, and hypochondriasis are more often present in the elderly depressed patients than in younger patients. The elderly people are also more likely than their younger counterparts to complain of insomnia.

Norrie disease: extraocular clinical manifestations in 56 patients.

PubMed

Smith, Sharon E; Mullen, Thomas E; Graham, Dionne; Sims, Katherine B; Rehm, Heidi L

2012-08-01

Norrie disease (ND) is an X-linked recessive disorder characterized by congenital blindness, progressive sensorineural hearing loss and cognitive impairment. The ocular phenotype has been well described, while the extraocular manifestations of the disorder are not well understood. We present the data from the Norrie Disease Registry, which consists of 56 patients with detailed clinical histories and genotype data. This study represents the largest, detailed investigation into the phenotypic spectrum of ND to date and more importantly expands knowledge of the extraocular clinical manifestations. We identify several novel aspects of the syndrome that will improve the management of these patients. In particular, we expand our understanding of the neurologic manifestations in ND and identify a chronic seizure disorder in approximately 10% of all patients. In addition, details of the hearing phenotype are described including the median age of onset (12 years of age) and how genotype affects onset. Moreover, we find vascular disease to be a significant component of ND; and vascular health should be, in the future, a component of patient clinical care. In summary, the results expand our understanding of the phenotypic variability and genotypic heterogeneity in ND patients. Copyright © 2012 Wiley Periodicals, Inc.

Real-Life Contextual Manifestations of Wisdom

ERIC Educational Resources Information Center

Yang, Shih-Ying

2008-01-01

Wisdom pertains to managing human affairs, and it arises in highly contextualized situations. The present study aims to investigate manifestations of wisdom in real-life contexts through semi-structured interviews with 66 individuals nominated as wise persons. All nominees were ethnic Chinese from Taiwan, an East Asian country which has…

Hypokalemic periodic paralysis; two different genes responsible for similar clinical manifestations

PubMed Central

Kim, Hunmin; Hwang, Hee; Cheong, Hae Il

2011-01-01

Primary hypokalemic periodic paralysis (HOKPP) is an autosomal dominant disorder manifesting as recurrent periodic flaccid paralysis and concomitant hypokalemia. HOKPP is divided into type 1 and type 2 based on the causative gene. Although 2 different ion channels have been identified as the molecular genetic cause of HOKPP, the clinical manifestations between the 2 groups are similar. We report the cases of 2 patients with HOKPP who both presented with typical clinical manifestations, but with mutations in 2 different genes (CACNA1Sp.Arg528His and SCN4A p.Arg672His). Despite the similar clinical manifestations, there were differences in the response to acetazolamide treatment between certain genotypes of SCN4A mutations and CACNA1S mutations. We identified p.Arg672His in the SCN4A gene of patient 2 immediately after the first attack through a molecular genetic testing strategy. Molecular genetic diagnosis is important for genetic counseling and selecting preventive treatment. PMID:22253645

19 CFR 122.48 - Air cargo manifest.

Code of Federal Regulations, 2014 CFR

2014-04-01

... aircraft, except that a more complete description of the cargo shipped may be provided by attaching to the... air express or freight shall be manifested as other air express or freight. (e) Accompanied baggage in...

Extra-cardiac manifestations of adult congenital heart disease.

PubMed

Gaeta, Stephen A; Ward, Cary; Krasuski, Richard A

2016-10-01

Advancement in correction or palliation of congenital cardiac lesions has greatly improved the lifespan of congenital heart disease patients, resulting in a rapidly growing adult congenital heart disease (ACHD) population. As this group has increased in number and age, emerging science has highlighted the systemic nature of ACHD. Providers caring for these patients are tasked with long-term management of multiple neurologic, pulmonary, hepatic, renal, and endocrine manifestations that arise as syndromic associations with congenital heart defects or as sequelae of primary structural or hemodynamic abnormalities. In this review, we outline the current understanding and recent research into these extra-cardiac manifestations. Copyright © 2016 Elsevier Inc. All rights reserved.

Ulcerative Lesions: A Rare Cutaneous Manifestation of Brucellosis.

PubMed

Azadi, Abbas; Jafarpour Fard, Payman; Almasian, Mohammad

2018-01-01

Brucellosis is a disease that is transmitted from animals to humans mainly via the consumption of unpasteurized dairy products, and it can involve any organ all over the body. Here, we report a significant rare case of brucellosis with cutaneous manifestations in a 52-year-old male patient whose disease was diagnosed via a serology test. The patient received standard antibiotic treatment, and his cutaneous lesions healed quickly. Although the cutaneous manifestations of brucellosis are exceedingly rare, in case of encountering ulcerative lesions and other cutaneous findings, particularly in endemic areas, infection with brucellosis should be kept in mind as an important differential diagnosis.

Review article: non-malignant oral manifestations in inflammatory bowel diseases.

PubMed

Katsanos, K H; Torres, J; Roda, G; Brygo, A; Delaporte, E; Colombel, J-F

2015-07-01

Patients with inflammatory bowel diseases (IBD) may present with lesions in their oral cavity. Lesions may be associated with the disease itself representing an extraintestinal manifestation, with nutritional deficiencies or with complications from therapy. To review and describe the spectrum of oral nonmalignant manifestations in patients with inflammatory bowel diseases [ulcerative colitis (UC), Crohn's disease (CD)] and to critically review all relevant data. A literature search using the terms and variants of all nonmalignant oral manifestations of inflammatory bowel diseases (UC, CD) was performed in November 2014 within Pubmed, Embase and Scopus and restricted to human studies. Oral lesions in IBD can be divided into three categories: (i) lesions highly specific for IBD, (ii) lesions highly suspicious of IBD and (iii) nonspecific lesions. Oral lesions are more common in CD compared to UC, and more prevalent in children. In adult CD patients, the prevalence rate of oral lesions is higher in CD patients with proximal gastrointestinal tract and/or perianal involvement, and estimated to range between 20% and 50%. Oral lesions can also occur in UC, with aphthous ulcers being the most frequent type. Oral manifestations in paediatric UC may be present in up to one-third of patients and are usually nonspecific. Oral manifestations in IBD can be a diagnostic challenge. Treatment generally involves managing the underlying intestinal disease. In cases presenting with local disabling symptoms and impaired quality of life, local and systemic medical therapy must be considered and/or oral surgery may be required. © 2015 John Wiley & Sons Ltd.

Manifestation of resonance-related chaos in coupled Josephson junctions

NASA Astrophysics Data System (ADS)

Shukrinov, Yu. M.; Hamdipour, M.; Kolahchi, M. R.; Botha, A. E.; Suzuki, M.

2012-11-01

Manifestation of chaos in the temporal dependence of the electric charge is demonstrated through the calculation of the maximal Lyapunov exponent, phase-charge and charge-charge Lissajous diagrams and correlation functions. It is found that the number of junctions in the stack strongly influences the fine structure in the current-voltage characteristics and a strong proximity effect results from the nonperiodic boundary conditions. The observed resonance-related chaos exhibits intermittency. The criteria for a breakpoint region with no chaos are obtained. Such criteria could clarify recent experimental observations of variations in the power output from intrinsic Josephson junctions in high temperature superconductors.

Extraintestinal Manifestations of Celiac Disease: Effectiveness of the Gluten-Free Diet.

PubMed

Jericho, Hilary; Sansotta, Naire; Guandalini, Stefano

2017-07-01

The aim of the study was to evaluate the effectiveness of the gluten-free diet (GFD) on extraintestinal symptoms in pediatric and adult celiac populations at the University of Chicago. We conducted a retrospective chart review of the University of Chicago Celiac Center clinic charts from January 2002 to October 2014. Demographics, serologic testing, intestinal biopsies, and extraintestinal symptoms at presentation, 12, 24, and >24 months were recorded. Extraintestinal symptoms included abnormal liver enzymes, arthralgia/arthritis, dermatitis herpetiformis, alopecia, fatigue, headache, anemia, stomatitis, myalgias, psychiatric disorders, rashes, seizures, neuropathy, short stature, delayed puberty, osteoporosis, and infertility. A total of 737 patients with biopsy-confirmed celiac disease or skin biopsy-confirmed dermatitis herpetiformis were included. Patients lost to follow-up, or with insufficient data were excluded leaving 328 patients (157 pediatrics younger than 18 years). For pediatrics, the female to male ratio was 2:1 and the mean age at diagnosis was 8.9 years. For adults, 4:1 and 40.6 years old. Extraintestinal symptom rates were similar in children (60%) and adults (62%). Short stature (33%), fatigue (28%), and headache (20%) were most common in children. Iron deficiency anemia (48%), fatigue (37%), and headache/psychiatric disorders (24%) were common in adults. Children had faster/higher rates of symptom resolution compared with adults. Twenty-eight percent of children with unresolved short stature on a GFD were found to have other comorbidities. Children and adults with celiac disease have similar rates of extraintestinal manifestations. In children short stature, fatigue, and headache were most common, whereas anemia, fatigue, and headache/psychiatric disorders were most common in adults. Children on a strict GFD showed faster and higher rates of symptom resolution as compared to adults. Unresponsive children with short stature must be assessed for

Imaging findings in systemic childhood diseases presenting with dermatologic manifestations.

PubMed

Fink, Adam Z; Gittler, Julia K; Nakrani, Radhika N; Alis, Jonathan; Blumfield, Einat; Levin, Terry L

Many childhood diseases often present with skin abnormalities with which radiologists are largely unfamiliar. Knowledge of associated dermatologic manifestations may aid the radiologist in confirming the diagnosis and recommending targeted imaging of affected organs. We review the imaging findings in childhood diseases associated with dermatologic manifestations. Diseases include dermatologic findings which herald underlying malignancy (Neuroblastoma, leukemia/lymphoma, Langerhans cell histiocytosis),are associated with risk of malignancy (Epidermolysis Bullosa, basal cell nevus syndrome, Cowden's syndrome, Tuberous Sclerosis),or indicate a systemic inflammatory/immune disorder (Kawasaki's disease, Henoch Schonlein Purpura, systemic lupus erythematosus, scleroderma, sarcoidosis, dermatomyositis and immune thrombocytopenic purpura). Familiarity with pertinent findings in childhood diseases presenting with dermatologic manifestations in childhood diseases aids the radiologist in confirming the diagnosis and guiding imaging workup. Copyright © 2017 Elsevier Inc. All rights reserved.

Coronal manifestations of preflare activity

NASA Technical Reports Server (NTRS)

Schmahl, E. J.; Webb, D. F.; Woodgate, B.; Waggett, P.; Bentley, R.; Hurford, G.; Schadee, A.; Schrijver, J.; Harrison, R.; Martens, P.

1986-01-01

A variety of coronal manifestations of precursors or preheating for flares are discussed. Researchers found that almost everyone with a telescope sees something before flares. Whether an all-encompassing scenario will ever be developed is not at all clear at present. The clearest example of preflare activity appears to be activated filaments and their manifestations, which presumably are signatures of a changing magnetic field. But researchers have seen two similar eruptions, one without any evidence of emerging flux (Kundu et al., 1985) and the other with colliding poles (Simon et al., 1984). While the reconnection of flux is generally agreed to be required to energize a flare, the emergence of flux from below (at least on short timescales and in compact regions) does not appear to be a necessary condition. In some cases the cancelling of magnetic flux (Martin, 1984) by horizontal motions instead may provide the trigger (Priest, 1985) Researchers found similarities and some differences between these and previous observations. The similarities, besides the frequent involvement of filaments, include compact, multiple precursors which can occur both at and near (not at) the flare site, and the association between coronal sources and activity lower in the atmosphere (i.e., transition zone and chromosphere).

19 CFR 123.22 - In-transit manifest.

Code of Federal Regulations, 2012 CFR

2012-04-01

... CBP RELATIONS WITH CANADA AND MEXICO Shipments in Transit Through Canada or Mexico § 123.22 In-transit... cars or other overland carriers transiting Mexico a manifest on Customs Form 7512-B or 7533-C shall be...

19 CFR 123.22 - In-transit manifest.

Code of Federal Regulations, 2010 CFR

2010-04-01

... CUSTOMS RELATIONS WITH CANADA AND MEXICO Shipments in Transit Through Canada or Mexico § 123.22 In-transit... cars or other overland carriers transiting Mexico a manifest on Customs Form 7512-B or 7533-C shall be...

[Effect of an introgression from Aegilops cylindrica host on manifestation of productivity traits in winter common wheat F2 plants].

PubMed

Kozub, N A; Sozinov, I A; sozinov, A A

2004-12-01

The effect of introgression of a chromosome 1D segment from Aegilops cylindrica to winter common wheat on productivity traits in F2 plants was studied using storage protein loci as genetic markers. An allele of the gliadin-coding Gli-D1 locus served as a marker of the introgression. Using of two- and three-locus interaction models, it was shown that the introgression tagged with Gli-D1 affected the manifestation of productivity traits (productive tillering, grain weight per plant and grain number per plant) through interaction with other marker storage protein loci: Glu-B1, Glu-D1, and Gli-B2.

Space Launch System Co-Manifested Payload Options for Habitation

NASA Technical Reports Server (NTRS)

Smitherman, David

2015-01-01

The Space Launch System (SLS) has a co-manifested payload capability that will grow over time as the rocket matures and planned upgrades are implemented. The final configuration is planned to be capable of inserting a payload greater than 10 metric tons (mt) into a trans-lunar injection trajectory along with the crew in the Orion capsule and the service module. The co-manifested payload is located below the Orion and its service module in a 10-meter high fairing similar to the way the Saturn launch vehicle carried the lunar lander below the Apollo command and service modules. A variety of approaches have been explored that utilizes this co-manifested payload capability to build up infrastructure in deep space in support of future asteroid, lunar, and Mars mission scenarios. This paper is a report on the findings from the Advanced Concepts Office study team at the NASA Marshall Space Flight Center, working with the Advanced Exploration Systems Program on the Exploration Augmentation Module Project. It includes some of the possible options for habitation in the co-manifested payload volume on SLS. Findings include module designs that can be developed in 10mt increments to support these missions, including overall conceptual layouts, mass properties, and approaches for integration into various scenarios for near-term support of deep space habitat research and technology development, support to asteroid exploration, and long range support for Mars transfer flights.

The role of ZFP580, a novel zinc finger protein, in TGF-mediated cytoprotection against chemical hypoxia-induced apoptosis in H9c2 cardiac myocytes

PubMed Central

Mao, Shi-Yun; Meng, Xiang-Yan; Xu, Zhong-Wei; Zhang, Wen-Cheng; Jin, Xiao-Han; Chen, Xi; Zhou, Xin; Li, Yu-Ming; Xu, Rui-Cheng

2017-01-01

Zing finger protein 580 (ZFP580) is a novel Cys2-His2 zinc-finger transcription factor that has an anti-apoptotic role in myocardial cells. It is involved in the endothelial transforming growth factor-β1 (TGF-β1) signal transduction pathway as a mothers against decapentaplegic homolog (Smad)2 binding partner. The aim of the present study was to determine the involvement of ZFP580 in TGF-β1-mediated cytoprotection against chemical hypoxia-induced apoptosis, using H9c2 cardiac myocytes. Hypoxia was chemically induced in H9c2 myocardial cells by exposure to cobalt chloride (CoCl2). In response to hypoxia, cell viability was decreased, whereas the expression levels of hypoxia inducible factor-1α and ZFP580 were increased. Pretreatment with TGF-β1 attenuated CoCl2-induced cell apoptosis and upregulated ZFP580 protein expression; however, these effects could be suppressed by SB431542, an inhibitor of TGF-β type I receptor and Smad2/3 phosphorylation. Furthermore, suppression of ZFP580 expression by RNA interference reduced the anti-apoptotic effects of TGF-β1 and thus increased CoCl2-induced apoptosis. B-cell lymphoma (Bcl)-2-associated X protein/Bcl-2 ratio, reactive oxygen species generation and caspase-3 activation were also increased following ZFP580 inactivation. In conclusion, these results indicate that ZFP580 is a component of the TGF-β1/Smad signaling pathway, and is involved in the protective effects of TGF-β1 against chemical hypoxia-induced cell apoptosis, through inhibition of the mitochondrial apoptotic pathway. PMID:28259939

Chronic polyarthritis as isolated manifestation of toxocariasis.

PubMed

Viola, Gabriela R; Giacomin, Maria Fernanda A; França, Camila M P; Sallum, Adriana M E; Jacob, Cristina M A; Silva, Clovis A

2016-01-01

Human toxocariasis is a parasitic zoonosis mainly caused by Toxocara canis or Toxocara cati and is acquired by ingestion of the parasite's embryonated eggs. Arthralgia and/or arthritis were reported in up to 17% of the cases, generally with acute duration (less than 6 weeks). However, to our knowledge, chronic polyarthritis, as the isolated presentation of Toxocara infection, was not reported. One of the 5809 patients that was followed up at our service (0.017%) had chronic polyarthritis as the single manifestation of toxocariasis and was described herein. A 3-year-old girl was referred to our service with severe painful chronic polyarthritis for a period longer than 10 weeks and morning stiffness of 30min. Dog contact exposure history in the recreational areas of neighborhood was reported. Her exams showed high levels of eosinophils in peripheral blood (29%), bone marrow aspirate revealed marked eosinophilia (32%) and Toxocara enzyme-linked immunosorbent assay (Elisa) was positive (1:1280). She was treated with paracetamol (40mg/kg/day) and thiabendazole (25mg/kg/day) for 10 days, and all manifestations reduced. After eight months of follow-up, she was on clinical and laboratorial remission. In conclusion, we described a case of chronic polyarthritis, as isolated manifestation of toxocariasis, mimicking juvenile idiopathic arthritis and leukemia. Importantly, this zoonosis should be considered in patients with arthritis and eosinophilia. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Clinical manifestations and management of Gaucher disease.

PubMed

Linari, Silvia; Castaman, Giancarlo

2015-01-01

Gaucher disease is a rare multi-systemic metabolic disorder caused by the inherited deficiency of the lysosomal enzyme β-glucocerebrosidase, which leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages with damage to haematological, visceral and bone systems. Anaemia, thrombocytopenia, enlargement of liver and/or spleen, skeletal abnormalities (osteopenia, lytic lesions, pathological fractures, chronic bone pain, bone crisis, bone infarcts, osteonecrosis and skeletal deformities) are typical manifestations of the most prevalent form of the disease, the so-called non-neuronopathic type 1. However, severity and coexistence of different symptoms are highly variable. The determination of deficient β-glucocerebrosidase activity in leukocytes or fibroblasts by enzymatic assay is the gold standard for the diagnosis of Gaucher disease. Comprehensive and reproducible evaluation and monitoring of all clinically relevant aspects are fundamental for the effective management of Gaucher disease patients. Enzyme replacement therapy has been shown to be effective in reducing glucocerebroside storage burden and diminishing the deleterious effects caused by its accumulation. Tailored treatment plan for each patient should be directed to symptom relief, general improvement of quality of life, and prevention of irreversible damage.

Effect of Tobacco Smoking on The Clinical, Histopathological, and Serological Manifestations of Sjögren’s Syndrome

PubMed Central

Stone, Donald U.; Fife, Dustin; Brown, Michael; Earley, Keith E.; Radfar, Lida; Kaufman, C. Erick; Lewis, David M.; Rhodus, Nelson L.; Segal, Barbara M.; Wallace, Daniel J.; Weisman, Michael H.; Venuturupalli, Swamy; Brennan, Michael T.; Lessard, Christopher J.; Montgomery, Courtney G.; Scofield, R. Hal; Sivils, Kathy L.

2017-01-01

Objectives To assess the association of smoking habits with the clinical, serological, and histopathological manifestations of Sjögren’s syndrome (SS) and non-Sjögren’s sicca (non-SS sicca). Methods Cross-sectional case-control study of 1288 patients with sicca symptoms (587 SS and 701 non-SS sicca) evaluated in a multi-disciplinary research clinic. Smoking patterns were obtained from questionnaire data and disease-related clinical and laboratory data were compared between current, past, ever, and never smokers. Results Current smoking rates were 4.6% for SS patients compared to 14.1% in non-SS sicca (p = 5.17x10E-09), 18% in a local lupus cohort (p = 1.13x10E-14) and 16.8% in the community (p = 4.12x10E-15). Current smoking was protective against SS classification (OR 0.35, 95%CI 0.22–0.56, FDR q = 1.9E10-05), focal lymphocytic sialadenitis (OR 0.26, 95%CI 0.15–0.44, FDR q = 1.52x10E-06), focus score ≥1 (OR 0.22, 95%CI 0.13–0.39, FDR q = 1.43x10E-07), and anti-Ro/SSA(+) (OR 0.36, 95%CI 0.2–0.64, FDR q = 0.0009); ever smoking was protective against the same features and against anti-La/SSB(+) (OR 0.52, 95%CI 0.39–0.70, FDR q = 5.82x10E-05). Duration of smoking was inversely correlated with SS even after controlling for socioeconomic status, BMI, alcohol and caffeine consumption. Conclusions Current tobacco smoking is negatively and independently associated with SS, protecting against disease-associated humoral and cellular autoimmunity. The overall smoking rate amongst SS patients is significantly lower than in matched populations and the effects of smoking are proportional to exposure duration. In spite of the protective effects of tobacco on SS manifestations, it is associated with other serious comorbidities such as lung disease, cardiovascular risk and malignancy, and should thus be strongly discouraged in patients with sicca. PMID:28166540

Cutaneous manifestations of non-Hodgkin's lymphoma.

PubMed

Kumar, S S; Kuruvilla, M; Pai, G S; Dinesh, M

2003-01-01

Thirty-two confirmed cases of non -Hodgkin's lymphoma (NHL) were examined for cutaneous manifestations for a period of 2 years from November 1998 in KMC Hospital Attavar, Mangalore. Cutaneous manifestations in the study group were compared to a control group of 32 patients. Specific infiltrates were present in all (5/5) CTCL patients and one out of twenty-seven patients with low grade NHL. Morphologically they presented as papules, plaques, nodules and erythroderma. Infective conditions seen in the study group were superficial fungal (7/32) and viral infections (2/ 32). Non-infective conditions were acquired ichthyosis (10/32), generalised pruritus (5/32), insect bite reaction (1/32) and drug eruption (1/32). When compared to control patients only acquired ichthyosis and generalised pruritus were found to be statistically significant. The study group also showed changes due to chemotherapy like diffuse alopecia (24/29), bluish pigmentation of proximal part of nail (4/29), localised pigmentation of palms and soles (1 /29), diffuse pigmentation at injection site (1 /29), pigmentation at scar site (1 /29) and stomatitis (4/29).

Ophthalmic manifestations of mucoceles.

PubMed

Avery, G; Tang, R A; Close, L G

1983-08-01

Two patients with mucoceles are described. The first case had exophthalmos, and the second had visual loss suggestive of retrobulbar optic neuritis. Possible ocular manifestations of mucoceles are discussed, and the computed tomography findings of these are shown. The treatment of mucoceles is reviewed, and it is stressed that a team approach involving ophthalmology, otorhinolaryngology, and radiology is essential for accurate diagnosis and treatment. Paranasal sinus mucoceles can present with a multitude of different symptoms. The type of presentation is usually determined by the original site of the mucocele, whether it be frontal, ethmoidal, or sphenoidal.

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

Quality of life in Huntington's disease: a comparative study investigating the impact for those with pre-manifest and early manifest disease, and their partners.

PubMed

Read, Joy; Jones, Rebecca; Owen, Gail; Leavitt, Blair R; Coleman, Allison; Roos, Raymund A C; Dumas, Eve M; Durr, Alexandra; Justo, Damian; Say, Miranda; Stout, Julie C; Tabrizi, Sarah J; Craufurd, David

2013-01-01

Given the multifaceted nature of this inherited neurodegenerative condition, typically affecting adults in mid-life, it is perhaps not surprising that studies indicate poorer Health Related Quality of Life (HrQoL) in those with the gene-expansion and, by association, in their families. This study aimed to extend the current literature by exploring specific life domains, including at an earlier disease stage than usually reported in the HRQoL literature, and in a subgroup of gene-negative partners. 355 participants from the TRACK-HD cohort (120 Controls, 118 Pre-HD and 117 early-HD) completed standardised self-report measures of HrQoL (SF36 and QoLI), underwent clinical assessments of capacity and motor function (UHDRS), semi structured interviews assessing neuropsychiatric symptoms (PBA-s), completed paper and computerized cognitive tasks and assessment of behaviours associated with damage to frontal brain circuits (FrSBe). Each gene-expanded group scored statistically significantly lower than gene-negative sibling controls on the SF36 General Health subscale; neuropsychiatric symptoms and executive dysfunction were associated with reduced HrQoL. Those with Stage II disease reported statistically significantly lower HrQoL than gene-negative controls across physical, emotional and social life domains. Those partnered with manifest participants reported lower HrQoL in the social domain compared to those partnered with at-risk participants furthest from disease onset; and perseverative symptoms in manifest partners were found to be related to lower HrQoL in their gene-negative partners. HrQoL in gene-negative partners of pre-manifest individuals was associated with pre-manifest individuals' neuropsychiatric and cognitive function. Understanding the nature and timing of disruption to the HrQoL in people who are pre-manifest and diagnosed with HD, and their gene-negative partners, can inform the development of appropriate strategies and interventions.

Radiologic manifestations in the musculoskeletal system of miscellaneous endocrine disorders.

PubMed

Chew, F S

1991-01-01

The manifestations of endocrine derangements in the musculoskeletal system in infancy and childhood are disturbances in growth and maturation and in adulthood are disturbances in maintenance and metabolism. Hypercortisolism during skeletal immaturity suppresses growth. In the adult, hypercortisolism leads to osteoporosis, osteonecrosis, and muscle wasting. Deficiency of growth hormone during skeletal development results in short stature. An excess of growth hormone in a skeletally immature individual results in gigantism, an excess in a skeletally mature individual results in acromegaly. Patients with gigantism have extreme height with normal body proportions. Musculoskeletal manifestations of acromegaly include soft-tissue thickening, vertebral body enlargement, characteristic hand and foot changes, and enthesal bony proliferation. Hyperthyroidism causes catabolism of protein and loss of connective tissue, which manifest as muscle wasting. Deficient levels of thyroid hormone cause defects in growth and development. Severe growth retardation from congenital hypothyroidism is rare because neonatal screening recognizes the disorder and leads to early treatment. The skeletal manifestation of hypergonadism in children is precocious growth and early skeletal maturation. Although the initial precocious growth spurt results in a tall child, early closure of the growth plates results in a short adult. Hypogonadism in the prepubertal child results in delayed adolescence and delayed skeletal maturation. Diabetes mellitus in childhood results in decreased growth, a phenomenon presumed to be secondary to nutritional abnormalities. Generalized osteoporosis and short stature are common. In the adult, generalized osteoporosis may accompany insulin-dependent diabetes mellitus if obesity is absent. Calcification of interdigital arteries of the foot is common in diabetics and uncommon in other conditions. Additional skeletal manifestations relate to complications of diabetes such as

[Atypical manifestations in familial type 1 Waardenburg syndrome].

PubMed

Sans, B; Calvas, P; Bazex, J

1998-01-01

Waardenburg syndrome is an uncommon genetic disorder. Four clinical types are recognized. Three responsible genes have been identified (PAX 3: for type I syndrome, MITF and EDN3 for types II and IV respectively). We report the case of a patient with Waardenburg type I morphotype who had atypical neurological manifestations. Decisive elements for diagnosis were the presence of Waardenburg syndrome in the family and, in affected kin, a mutation causing a shift in PAX 3 gene reading. This case confirms the variability of Waardenburg signs within one family. The association of unusual neurological manifestations in the proband suggested that Vogt Koyanagi Harada disease may have been associated and may show some relationship with familial Waardenburg syndrome.

Advancements in Pharmacotherapy for Noncancerous Manifestations of HPV

PubMed Central

Kollipara, Ramya; Ekhlassi, Erfon; Downing, Christopher; Guidry, Jacqueline; Lee, Michael; Tyring, Stephen K.

2015-01-01

Human papillomavirus (HPV) is the most common sexually transmitted disease. Via infection of the basal epithelial cells, HPV causes numerous malignancies and noncancerous cutaneous manifestations. Noncancerous cutaneous manifestations of HPV, including common, plantar, plane, and anogenital warts, are among the most common reasons for an office visit. Although there are various therapies available, they are notoriously difficult to treat. HPV treatments can be grouped into destructive (cantharidin, salicylic acid), virucidal (cidofovir, interferon-α), antimitotic (bleomycin, podophyllotoxin, 5-fluorouracil), immunotherapy (Candida antigen, contact allergen immunotherapy, imiquimod) or miscellaneous (trichloroacetic acid, polyphenon E). The mechanism of action, recent efficacy data, safety profile and recommended regimen for each of these treatment modalities is discussed. PMID:26239450

19 CFR 122.74 - Incomplete (pro forma) manifest.

Code of Federal Regulations, 2010 CFR

2010-04-01

... OF THE TREASURY AIR COMMERCE REGULATIONS Documents Required for Clearance and Permission To Depart; Electronic Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial...

Gastrointestinal manifestations of mitochondrial disorders: a systematic review

PubMed Central

Finsterer, Josef; Frank, Marlies

2016-01-01

Mitochondrial disorders (MIDs) due to respiratory-chain defects or nonrespiratory chain defects are usually multisystem conditions [mitochondrial multiorgan disorder syndrome (MIMODS)] affecting the central nervous system (CNS), peripheral nervous system, eyes, ears, endocrine organs, heart, kidneys, bone marrow, lungs, arteries, and also the intestinal tract. Frequent gastrointestinal (GI) manifestations of MIDs include poor appetite, gastroesophageal sphincter dysfunction, constipation, dysphagia, vomiting, gastroparesis, GI pseudo-obstruction, diarrhea, or pancreatitis and hepatopathy. Rare GI manifestations of MIDs include dry mouth, paradontosis, tracheoesophageal fistula, stenosis of the duodeno-jejunal junction, atresia or imperforate anus, liver cysts, pancreas lipomatosis, pancreatic cysts, congenital stenosis or obstruction of the GI tract, recurrent bowel perforations with intra-abdominal abscesses, postprandial abdominal pain, diverticulosis, or pneumatosis coli. Diagnosing GI involvement in MIDs is not at variance from diagnosing GI disorders due to other causes. Treatment of mitochondrial GI disease includes noninvasive or invasive measures. Therapy is usually symptomatic. Only for myo-neuro-gastro-intestinal encephalopathy is a causal therapy with autologous stem-cell transplantation available. It is concluded that GI manifestations of MIDs are more widespread than so far anticipated and that they must be recognized as early as possible to initiate appropriate diagnostic work-up and avoid any mitochondrion-toxic treatment. PMID:28286566

Respiratory manifestations of gastro-oesophageal reflux in children.

PubMed

de Benedictis, Fernando Maria; Bush, Andrew

2018-03-01

Gastro-oesophageal reflux disease (GORD) is a complex problem in children. Suspected respiratory manifestations of GORD, such as asthma, chronic cough and laryngitis, are commonly encountered in the paediatric practice, but continue to be entities with more questions than answers. The accuracy of diagnostic tests (ie, pH or pH-impedance monitoring, laryngoscopy, endoscopy) for patients with suspected extraoesophageal manifestations of GORD is suboptimal and therefore whether there is a causal relationship between these conditions remains largely undetermined. An empiric trial of proton pump inhibitors can help individual children with undiagnosed respiratory symptoms and suspicion of GORD, but the response to therapy is unpredictable, and in any case what may be being observed is spontaneous improvement. Furthermore, the safety of these agents has been called into question. Poor response to antireflux therapy is an important trigger to search for non-gastro-oesophageal reflux causes for patients' symptoms. Evidence for the assessment of children with suspected extraoesophageal manifestations of GORD is scanty and longitudinal studies with long-term follow-up are urgently required. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pulmonary manifestations of Birt-Hogg-Dubé syndrome

PubMed Central

Seyama, Kuniaki; McCormack, Francis X.

2015-01-01

Birt-Hogg-Dubé syndrome (BHD) is a rare, autosomal dominant disorder characterized by the development of hair follicle tumors, renal tumors and pulmonary cysts. BHD is caused by heterozygous, predominantly truncating mutations in the folliculin (FLCN) gene located on chromosome 17, which encodes a highly conserved tumor suppressor protein. Although management of renal tumors of low malignant potential is the primary focus of longitudinal care, pulmonary manifestations including cyst formation and spontaneous pneumothorax are among the most common manifestations in BHD. Due to the lack of awareness, there is commonly a delay in the pulmonary diagnosis of BHD and patients are frequently mislabeled as having chronic obstructive lung disease, emphysema or common bullae/blebs. A family history of pneumothorax is present in 35 % of patients with BHD. Certain imaging characteristics of the cysts, including size, basilar and peripheral predominance, perivascular and periseptal localization, and elliptical or lentiform shape can suggest the diagnosis of BHD based on inspection of the chest CT scan alone. Recurrent pneumothoraces are common and early pleurodesis is recommended. A better understanding of role of FLCN in pulmonary cyst formation and long term studies to define the natural history of the pulmonary manifestations of BHD are needed. PMID:23715758

Neuropathological Basis of Non-Motor Manifestations of Parkinson’s Disease

PubMed Central

Adler, Charles H.; Beach, Thomas G.

2016-01-01

Non-motor manifestations of Parkinson’s disease (PD) can begin well before motor PD begins. It is now clear, from clinical and autopsy studies, that there is significant Lewy type alpha-synucleinopathy present outside the nigro-striatal pathway, and that this may underlie these non-motor manifestations. This review will discuss neuropathological findings that may underlie non-motor symptoms that either predate motor findings or occur as the disease progresses. PMID:27030013

49 CFR 172.205 - Hazardous waste manifest.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Hazardous waste manifest. 172.205 Section 172.205 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS HAZARDOUS MATERIALS TABLE, SPECIAL PROVISIONS, HAZARDOUS MATERIALS...

Cardiac and Vascular Synergic Protective Effect of Olea europea L. Leaves and Hibiscus sabdariffa L. Flower Extracts.

PubMed

Micucci, Matteo; Malaguti, Marco; Toschi, Tullia Gallina; Di Lecce, Giuseppe; Aldini, Rita; Angeletti, Andrea; Chiarini, Alberto; Budriesi, Roberta; Hrelia, Silvana

2015-01-01

This study was aimed at investigating the cardiovascular effects of an Olea europea L. leaf extract (OEE), of a Hibiscus sabdariffa L. flower extract (HSE), and of their 13 : 2 w/w mixture in order to assess their cardiac and vascular activity. Both extracts were fully characterized in their bioactive compounds by HPLC-MS/MS analysis. The study was performed using primary vascular endothelial cells (HUVECs) to investigate the antioxidant and cytoprotective effect of the extracts and their mixture and isolated guinea-pig left and right atria and aorta to evaluate the inotropic and chronotropic activities and vasorelaxant properties. In cultured HUVECs, OEE and HSE reduced intracellular reactive oxygen species formation and improved cell viability, following oxidative stress in dose-dependent manner. OEE and HSE exerted negative inotropic and vasorelaxant effects without any chronotropic property. Interestingly, the mixture exerted higher cytoprotective effects and antioxidant activities. Moreover, the mixture exerted an inotropic effect similar to each single extract, while it revealed an intrinsic negative chronotropic activity different from the single extract; its relaxant activity was higher than that of each single extract. In conclusion OEE and HSE mixture has a good potential for pharmaceutical and nutraceutical application, thanks to the synergistic effects of the single phytochemicals.

Cardiac and Vascular Synergic Protective Effect of Olea europea L. Leaves and Hibiscus sabdariffa L. Flower Extracts

PubMed Central

Micucci, Matteo; Gallina Toschi, Tullia; Di Lecce, Giuseppe; Aldini, Rita; Angeletti, Andrea; Chiarini, Alberto

2015-01-01

This study was aimed at investigating the cardiovascular effects of an Olea europea L. leaf extract (OEE), of a Hibiscus sabdariffa L. flower extract (HSE), and of their 13 : 2 w/w mixture in order to assess their cardiac and vascular activity. Both extracts were fully characterized in their bioactive compounds by HPLC-MS/MS analysis. The study was performed using primary vascular endothelial cells (HUVECs) to investigate the antioxidant and cytoprotective effect of the extracts and their mixture and isolated guinea-pig left and right atria and aorta to evaluate the inotropic and chronotropic activities and vasorelaxant properties. In cultured HUVECs, OEE and HSE reduced intracellular reactive oxygen species formation and improved cell viability, following oxidative stress in dose-dependent manner. OEE and HSE exerted negative inotropic and vasorelaxant effects without any chronotropic property. Interestingly, the mixture exerted higher cytoprotective effects and antioxidant activities. Moreover, the mixture exerted an inotropic effect similar to each single extract, while it revealed an intrinsic negative chronotropic activity different from the single extract; its relaxant activity was higher than that of each single extract. In conclusion OEE and HSE mixture has a good potential for pharmaceutical and nutraceutical application, thanks to the synergistic effects of the single phytochemicals. PMID:26180582

Glycyl-alanyl-histidine protects PC12 cells against hydrogen peroxide toxicity.

PubMed

Shimura, Hideki; Tanaka, Ryota; Shimada, Yoshiaki; Yamashiro, Kazuo; Hattori, Nobutaka; Urabe, Takao

2017-11-22

Peptides with cytoprotective functions, including antioxidants and anti-infectives, could be useful therapeutics. Carnosine, β-alanine-histidine, is a dipeptide with anti-oxidant properties. Tripeptides of Ala-His-Lys, Pro-His-His, or Tyr-His-Tyr are also of interest in this respect. We synthesized several histidine-containing peptides including glycine or alanine, and tested their cytoprotective effects on hydrogen peroxide toxicity for PC12 cells. Of all these peptides (Gly-His-His, Ala-His-His, Ala-His-Ala, Ala-Ala-His, Ala-Gly-His, Gly-Ala-His (GAH), Ala-His-Gly, His-Ala-Gly, His-His-His, Gly-His-Ala, and Gly-Gly-His), GAH was found to have the strongest cytoprotective activity. GAH decreased lactate dehydrogenase (LDH) leakage, apoptosis, morphological changes, and nuclear membrane permeability changes against hydrogen peroxide toxicity in PC12 cells. The cytoprotective activity of GAH was superior to that of carnosine against hydrogen peroxide toxicity in PC12 cells. GAH also protected PC12 cells against damage caused by actinomycin D and staurosporine. Additionally, it was found that GAH also protected SH-SY5Y and Jurkat cells from damage caused by hydrogen peroxide, as assessed by LDH leakage. Thus, a novel tripeptide, GAH, has been identified as having broad cytoprotective effects against hydrogen peroxide-induced cell damage.

[Free radicals in the origin and clinical manifestation of Down's syndrome].

PubMed

Arbuzova, S B

1996-01-01

The high level of free radicals and antioxidant protection disbalancing cause the chromosome nondisjunction in meiosis, appearance of trisomy 21 and fetuses with Down's syndrome, age-dependent pathology, of parent's mosaic clone, clinical manifestations of the syndrome, diseases in relatives, recurrent cases of trisomy 21. The comparative analysis of clinical traits of Down's syndrome and pathological changes in families with after-effects of radiation exposure was carried out. The factors causing an increase in the level of free radicals were considered.

Clinical manifestation and molecular genetic characterization of MYH9 disorders.

PubMed

Provaznikova, Dana; Geierova, Vera; Kumstyrova, Tereza; Kotlin, Roman; Mikulenkova, Dana; Zurkova, Kamila; Matoska, Vaclav; Hrachovinova, Ingrid; Rittich, Simon

2009-08-01

Currently, the May-Hegglin anomaly (MHA), Sebastian (SBS), Fechtner (FTNS) and Epstein (EPS) syndrome are considered to be distinct clinical manifestations of a single disease caused by mutations of the MYH9 gene encoding the heavy chain of non-muscle myosin IIA (NMMHC-IIA). Manifestations of these disorders include giant platelets, thrombocytopenia and combinations of the presence of granulocyte inclusions, deafness, cataracts and renal failure. We examined 15 patients from 10 unrelated families on whom we performed immunostaining of NMMHC-IIA in blood samples. Polymerase chain reaction (PCR) analysis of selected exons of the MYH9 gene revealed mutations in nine samples with one novel mutation. Results of fluorescence and mutational analysis were compared with clinical manifestations of the MYH9 disorder. We also determined the number of glycoprotein sites on the surface of platelets. Most patients had an increased number of glycoproteins, which could be due to platelet size.

Case report of Graves’ disease manifesting with odynophagia and heartburn

PubMed Central

Evsyutina, Yulia; Trukhmanov, Alexander; Ivashkin, Vladimir; Storonova, Olga; Godjello, Elina

2015-01-01

Graves’ disease is an autoimmune disease, which can manifest with a variety of extrathyroidal clinical syndromes like ophthalmopathy, pretibial myxedema (dermopathy), acropathy, cardiomyopathy, and encephalopathy. Though quite rare, this disease can also manifest with gastrointestinal symptoms such as dysphagia, heartburn, nausea, vomiting and diarrhea. We report a clinical case of Graves’ disease manifesting with dysfunction of the esophagus and heartburn in a 61-year-old man. In the muscular layer of the esophagus we found dystrophic changes led to its atony, which was documented by endoscopy and high-resolution manometry. The pathology features of esophageal symptoms were: focal proliferation of the basal cells, vascular distension, and dystrophy of the epithelial cells. Antithyroid treatment led to decrease of all clinical symptoms after 5 d of Thiamazole administration. Complete restoration of peristalsis in the esophagus, according to manometry, was observed in 1 mo after initiation of treatment. PMID:26730171

Case report of Graves' disease manifesting with odynophagia and heartburn.

PubMed

Evsyutina, Yulia; Trukhmanov, Alexander; Ivashkin, Vladimir; Storonova, Olga; Godjello, Elina

2015-12-28

Graves' disease is an autoimmune disease, which can manifest with a variety of extrathyroidal clinical syndromes like ophthalmopathy, pretibial myxedema (dermopathy), acropathy, cardiomyopathy, and encephalopathy. Though quite rare, this disease can also manifest with gastrointestinal symptoms such as dysphagia, heartburn, nausea, vomiting and diarrhea. We report a clinical case of Graves' disease manifesting with dysfunction of the esophagus and heartburn in a 61-year-old man. In the muscular layer of the esophagus we found dystrophic changes led to its atony, which was documented by endoscopy and high-resolution manometry. The pathology features of esophageal symptoms were: focal proliferation of the basal cells, vascular distension, and dystrophy of the epithelial cells. Antithyroid treatment led to decrease of all clinical symptoms after 5 d of Thiamazole administration. Complete restoration of peristalsis in the esophagus, according to manometry, was observed in 1 mo after initiation of treatment.

Structures, physicochemical and cytoprotective properties of new oxidovanadium(IV) complexes -[VO(mIDA)(dmbipy)]·1.5H2O and [VO(IDA)(dmbipy)]·2H2O

NASA Astrophysics Data System (ADS)

Drzeżdżon, Joanna; Jacewicz, Dagmara; Wyrzykowski, Dariusz; Inkielewicz-Stępniak, Iwona; Sikorski, Artur; Tesmar, Aleksandra; Chmurzyński, Lech

2017-09-01

New oxidovanadium(IV) complexes with a modification of the ligand in the VO2+ coordination sphere were synthesized. [VO(mIDA)(dmbipy)]•1.5H2O and [VO(IDA)(dmbipy)]•2H2O were obtained as dark green crystals and grey-green powder, respectively (mIDA = N-methyliminodiacetic anion, IDA = iminodiacetic anion, dmbipy = 4,4‧-dimethoxy-2,2‧-dipyridyl). The crystal structure of [VO(mIDA)(dmbipy)]·1.5H2O has been determined by the X-ray diffraction method. The studies of structure of [VO(mIDA)(dmbipy)]•1.5H2O have shown that this compound occurs in the crystal as two rotational conformers. Furthermore, the stability constants of [VO(mIDA)(dmbipy)]•1.5H2O and [VO(IDA)(dmbipy)]•2H2O complexes in aqueous solutions were studied by using the potentiometric titration method and, consequently, determined using the Hyperquad2008 program. Moreover, the title complexes were investigated as antioxidant substances. The impact of the structure modification in the VO2+ complexes on the radical scavenging activity has been studied. The ability to scavenge the superoxide radical by two complexes - [VO(mIDA)(dmbipy)]·1.5H2O and [VO(IDA)(dmbipy)]·2H2O was studied by cyclic voltammetry (CV) and nitrobluetetrazolium (NBT) methods. The title complexes were also examined by the spectrophotometric method as scavengers of neutral organic radical - 1,1-diphenyl-2-picrylhydrazyl (DPPH•) and radical cation - 2,2'-azinobis-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS•+). Furthermore, the biological properties of two oxidovanadium(IV) complexes were investigated in relation to its cytoprotective properties by the MTT and LDH tests based on the hippocampal HT22 neuronal cell line during the oxidative damage induced by hydrogen peroxide. Finally, the results presented in this paper have shown that the both new oxidovanadium(IV) complexes with the 4,4‧-dimethoxy-2,2‧-dipyridyl ligand can be treated as the cytoprotective substances.

Protective effects of essential oil of Citrus limon against aspirin-induced toxicity in IEC-6 cells.

PubMed

Bouzenna, Hafsia; Hfaiedh, Najla; Giroux-Metges, Marie-Agnès; Elfeki, Abdelfattah; Talarmin, Hélène

2017-05-01

Aspirin, one of the widely used nonsteroidal anti-inflammatory drugs, is the most highly consumed pharmaceutical product in the world. However, it has several side effects in cells. This study was designed to investigate the antioxidative activity and cytoprotective effects of essential oil of Citrus limon (EOC) extracted from leaves against aspirin-induced damages in the rat small intestine epithelial cells (IEC-6). Biochemical indicators were used to assess cytotoxicity and oxidative damages caused by aspirin treatment on IEC-6. Our results showed that the chemical characterization of EOC identified 25 compounds representing 98.19% of the total oil. The major compounds from this oil were z-citral (53.21%), neryl acetate (13.06%), geranyl acetate (10.33%), and limonene (4.23%). Aspirin induced a decrease in cell viability as well as an increase in superoxide dismutase (SOD) and catalase (CAT) activities. Contrariwise, the co-exposure of cells to aspirin and EOC alleviated every above syndrome by an increase in cell survival and decrease in SOD and CAT activities. In conclusion, the essential oil of C. limon has a potent cytoprotective effect against aspirin-induced toxicity in IEC-6 cells.

The effect of diltiazem on the manifestations of hyperthyroidism and thyroid function tests.

PubMed

Keleştimur, F; Aksu, A

1996-01-01

The aim of this study is to evaluate the effect of diltiazem on the symptoms and signs of hyperthyroidism and thyroid function tests and to assess whether diltiazem can be used associated with an anti-thyroid drug, propylthiouracil. Twenty-two patients with hyperthyroidism were included in a prospective, randomized and placebo controlled study. Group 1 (n:12) patients received diltiazem, 60 mg twice a day, for 30 days. Group 2 (n:10) patients received placebo for 30 days. The patients in both groups were given propylthiouracil, 100 mg three times a day, for the last 20 days of the study period. The patients remained in the hospital during the first 10 days. A standardized hyperthyroid symptom score (HSS) and thyroid function tests including thyroid-stimulating hormone (TSH), free thyroxine (free T4), free triiodothyronine (free T3), total thyroxine (T4) and total triiodothyronine (T3) were evaluated before and after 10 and 30 days of the study period. HSS decreased from 27.80 +/- 4.54 to 22.51 +/- 4.04 after 10 days of diltiazem therapy in Group 1 (p < 0.01). But there was no change in HSS in Group 2 (p > 0.01). No significant changes in thyroid function tests have occurred in both groups after 10 days of treatment. Diltiazem can be used in patients with hyperthyroidism to alleviate adrenergic manifestations. It can also be safely combined with propylthiouracil.

Minimal Brain Dysfunction Child: Some Clinical Manifestations, Definitions, Descriptions and Remediation Approaches.

ERIC Educational Resources Information Center

Stock, Claudette, Comp.

Remediation of learning disabilities is discussed and a table of teaching materials related to psychological and motor functions is provided. Guides on 11 behavioral manifestations and three specific learning disabilities furnish definitions and description as well as techniques for training and management. Behavioral manifestations considered…

Patterns of salivary cortisol levels can manifest work stress in emergency care providers.

PubMed

Nakajima, Yasushi; Takahashi, Takayuki; Shetty, Vivek; Yamaguchi, Masaki

2012-05-01

To develop objective assessments of work fatigue, we investigated the patterns of changes in salivary cortisol levels in emergency care providers working extended work shifts. Fourteen subjects, comprising seven physicians and seven physician assistants, provided unstimulated saliva samples at regular intervals over the course of a 24-h work shift and over their subsequent free day. There was a significant time effect, with early morning cortisol levels being significantly attenuated following the work shift. Native diurnal variations varied by gender, with the female subjects manifesting greater cortisol levels. Physicians also had higher cortisol profiles even though their wake-rest cycles were similar to those of the physician assistants. Our results suggest that temporal changes, as well as diurnal similarities, in the salivary cortisol patterns can reflect work-related stress and recovery. In particular, early morning cortisol levels may manifest individual reactivity to work stressors as well as sleep deprivation.

Pharyngeal manifestations of gastroesophageal reflux disease.

PubMed

Rubesin, Stephen E; Levine, Marc S

2018-06-01

This article discusses the extraesophageal manifestations of gastroesophageal reflux disease, focusing primarily on the gamut of pharyngeal abnormalities that can be detected on barium swallows. Abnormalities of pharyngeal swallowing caused by gastroesophageal reflux are illustrated. We particularly emphasize how pharyngoesophageal relationships can guide the radiologist for performing tailored barium swallows to optimally evaluate pharyngeal abnormalities in patients with underlying gastroesophageal reflux disease.

Anti-ganglioside antibodies in patients with systemic lupus erythematosus and neurological manifestations.

PubMed

Labrador-Horrillo, M; Martinez-Valle, F; Gallardo, E; Rojas-Garcia, R; Ordi-Ros, J; Vilardell, M

2012-05-01

Anti-ganglioside antibodies (AGA) have been associated with several peripheral neuropathies, such as Miller-Fisher syndrome, Guillain-Barré syndrome and multifocal motor neuropathy. They have also been studied in patients with systemic lupus erythematosus (SLE), focusing on neuropsychiatric manifestations and peripheral neuropathy, but the results are contradictory. To study the presence of AGA in a large cohort of patients with SLE and neuropsychiatric manifestations. Serum from 65 consecutive patients with SLE and neuropsychiatric manifestations, collected from 1985 to 2009, was tested for the presence of AGA antibodies (GM1, GM2, GM3, asialo-GM1 GD1a, GD1b, GD3, GT1b, GQ1b) using a standard enzyme-linked immunosorbent assay ELISA test (INCAT 1999) and thin layer chromatography (TLC). Positive results for asialo-GM1 (IgM) were found in 10 patients, 6 were positive for asialo-GM1 (IgM and IgG), and 4 were positive for other AGA such as GM1, GM2, GM3, GD1b, GT1b, GD3, (mainly IgM). Clinical and statistical studies showed no correlation between AGA and neuropsychiatric manifestations of SLE. Although some patients showed reactivity to AGA, these antibodies are not a useful marker of neuropsychiatric manifestations in SLE patients.

What rheumatologists should know about orofacial manifestations of autoimmune rheumatic diseases.

PubMed

Abrão, Aline Lauria Pires; Santana, Caroline Menezes; Bezerra, Ana Cristina Barreto; Amorim, Rivadávio Fernandes Batista de; Silva, Mariana Branco da; Mota, Licia Maria Henrique da; Falcão, Denise Pinheiro

Orofacial manifestations occur frequently in rheumatic diseases and usually represent early signs of disease or of its activity that are still neglected in clinical practice. Among the autoimmune rheumatic diseases with potential for oral manifestations, rheumatoid arthritis (RA), inflammatory myopathies (IM), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), relapsing polychondritis (RP) and Sjögren's syndrome (SS) can be cited. Signs and symptoms such as oral hyposalivation, xerostomia, temporomandibular joint disorders, lesions of the oral mucosa, periodontal disease, dysphagia, and dysphonia may be the first expression of these rheumatic diseases. This article reviews the main orofacial manifestations of rheumatic diseases that may be of interest to the rheumatologist for diagnosis and monitoring of autoimmune rheumatic diseases. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

What rheumatologists should know about orofacial manifestations of autoimmune rheumatic diseases.

PubMed

Abrão, Aline Lauria Pires; Santana, Caroline Menezes; Bezerra, Ana Cristina Barreto; Amorim, Rivadávio Fernandes Batista de; Silva, Mariana Branco da; Mota, Licia Maria Henrique da; Falcão, Denise Pinheiro

2016-02-11

Orofacial manifestations occur frequently in rheumatic diseases and usually represent early signs of disease or of its activity that are still neglected in clinical practice. Among the autoimmune rheumatic diseases with potential for oral manifestations, rheumatoid arthritis (RA), inflammatory myopathies (IM), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), relapsing polychondritis (RP) and Sjögren's syndrome (SS) can be cited. Signs and symptoms such as oral hyposalivation, xerostomia, temporomandibular joint disorders, lesions of the oral mucosa, periodontal disease, dysphagia, and dysphonia may be the first expression of these rheumatic diseases. This article reviews the main orofacial manifestations of rheumatic diseases that may be of interest to the rheumatologist for diagnosis and monitoring of autoimmune rheumatic diseases. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

LYMPHOBLASTOMAS IN CHILDHOOD—Cutaneous Manifestations

PubMed Central

Nelson, Lawrence M.

1953-01-01

The lymphoblastomas occurring in childhood are divided for purposes of discussion into lymphocytoma cutis, mycosis fungoides, lymphosarcoma, Hodgkin's disease, and leukemia. The cutaneous lesions may be either specific (as a result of the infiltration of the skin with specific cells of the conditions) or toxic (non-specific). With the possible exception of mycosis fungoides, the cutaneous manifestations are not diagnostic. The final diagnosis depends upon microscopic examination of the specific tissue involved and the coordination of the clinical and microscopic findings. PMID:13032796

Manifestations of Surface States in the Longitudinal Magnetoresistance of an Array of Bi Nanowires

NASA Astrophysics Data System (ADS)

Latyshev, Yu. I.; Frolov, A. V.; Volkov, V. A.; Wade, T.; Prudkoglyad, V. A.; Orlov, A. P.; Pudalov, V. M.; Konczykowski, M.

2018-04-01

The longitudinal magnetoresistance of the array of parallel-oriented bismuth nanowires each 100 nm in diameter grown by electrochemical deposition in nanopores of an Al2O3 membrane has been studied in magnetic fields up to 14 T and at temperatures down to 0.3 K. The resistance increases with the field and reaches a broad maximum in fields about 10 T. An anomalous increase in the resistance in weak fields is qualitatively consistent with the suppression of the antilocalization correction to the resistance, and the maximum is qualitatively associated with the classical size effect. Near the maximum at temperatures below 0.8 K, manifestations of reproducible magneto-oscillations of the resistance, which are periodic in field, have been detected. The period of these oscillations is close to a value corresponding to the passage of the flux quantum hc/ e through the section of a nanowire. The Fourier analysis also confirms that the oscillations are periodic. This result is similar to the manifestation the Aharonov-Bohm effect caused by conducting surface states of Dirac fermions occupying L-valleys of bismuth.

Less common clinical manifestations of atopic dermatitis: prevalence by age.

PubMed

Julián-Gónzalez, Rolando Elias; Orozco-Covarrubias, Luz; Durán-McKinster, Carola; Palacios-Lopez, Carolina; Ruiz-Maldonado, Ramon; Sáez-de-Ocariz, Marimar

2012-01-01

The common manifestations of atopic dermatitis (AD) appear sequentially with involvement of the cheeks in infancy, flexural extremities in childhood, and hands in adulthood. Although less common clinical manifestations are well described, they have not been the subject of epidemiologic studies to describe their prevalence in specific age groups. This observational, cross-sectional, comparative study included 131 children younger than 18 of both sexes with AD who attended the clinics of the Dermatology Department of the National Institute of Pediatrics in Mexico City. Patients were examined to determine the presence of infrequent clinical manifestations of AD during infancy, preschool and school age, and adolescence and stratified according to sex, age, and number of clinical signs. A chi-square test was used to detect differences according to age and sex. Logistic regression analysis was also performed. The main findings according to age were genital dermatitis and papular-lichenoid dermatitis variant in infants; atopic feet, prurigo-like, nummular pattern, and erythroderma in preschool and school-aged children; and eyelid eczema and nipple dermatitis in adolescents. The risk of development of nipple dermatitis and eyelid eczema increased with age, and the development of genital dermatitis decreased with age. The knowledge of the prevalence of less common clinical manifestations of AD according to age in different populations might be helpful in diagnosing incipient cases of AD. © 2012 Wiley Periodicals, Inc.

Antiphospholipid antibodies and non-thrombotic manifestations of systemic lupus erythematosus.

PubMed

İlgen, U; Yayla, M E; Ateş, A; Okatan, İ E; Yurteri, E U; Torgutalp, M; Keleşoğlu, A B D; Turgay, T M; Kınıklı, G

2018-04-01

Objectives The aim of this study was to investigate the association between antiphospholipid antibodies and non-thrombotic and non-gestational manifestations of systemic lupus erythematosus. Methods Systemic lupus erythematosus patients with persistently positive antiphospholipid antibodies or lupus anticoagulant were identified and grouped as systemic lupus erythematosus with antiphospholipid syndrome (SLE-APS), systemic lupus erythematosus with positive antiphospholipid antibodies/lupus anticoagulant without antiphospholipid syndrome (SLE-aPL), and systemic lupus erythematosus with negative aPLs (SLE-No aPL). Groups were compared in terms of non-thrombotic systemic lupus erythematosus manifestations and laboratory features retrospectively. Results A total of 150 systemic lupus erythematosus patients, 26 with SLE-APS, 25 with SLE-aPL, and 99 with SLE-No aPL, were identified. Livedo reticularis, neurologic involvement, and thrombocytopenia were more common in antiphospholipid antibody positive systemic lupus erythematosus cases. Malar rash, arthritis, and pleuritis were more common in the SLE-No aPL, SLE-APS, and SLE-aPL groups, respectively. Positivity rates and titers of specific antiphospholipid antibodies did not differ between the SLE-APS and SLE-aPL groups. Conclusions Presence of antiphospholipid syndrome or persistent antiphospholipid antibodies may be related to non-thrombotic and non-gestational systemic lupus erythematosus manifestations. Patients with systemic lupus erythematosus plus antiphospholipid syndrome and persistent antiphospholipid antibodies without antiphospholipid syndrome also differ in terms of systemic lupus erythematosus manifestations.

19 CFR 122.74 - Incomplete (pro forma) manifest.

Code of Federal Regulations, 2011 CFR

2011-04-01

...; Electronic Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial... proclamation of the President that a state of war exists between foreign nations; or (2) If the aircraft is...

PATTERN OF CUTANEOUS MANIFESTATIONS IN DIABETES MELLITUS

PubMed Central

Goyal, Abhishek; Raina, Sujeet; Kaushal, Satinder S; Mahajan, Vikram; Sharma, Nand Lal

2010-01-01

Background: Diabetes mellitus affects individuals of all ages and socioeconomic status. Skin is affected by the acute metabolic derangements as well as by chronic degenerative complications of diabetes. Aims: To evaluate the prevalence of skin manifestations in patients with diabetes mellitus. To analyze the prevalence and pattern of skin disorders among diabetic patients from this region of Western Himalayas. Materials and Methods: One hundred consecutive patients with the diagnosis of diabetes mellitus and having skin lesions, either attending the diabetic clinic or admitted in medical wards were included in this study. Results: The common skin disorders were: Xerosis (44%), diabetic dermopathy (36%), skin tags (32%), cutaneous infections (31%), and seborrheic keratosis (30%). Conclusion: Skin is involved in diabetes quite often and the manifestations are numerous. High prevalence of xerosis in our diabetic population is perhaps due to cold and dry climatic conditions in the region for most of the time in the year. PMID:20418975

Acute dacryocystitis: another clinical manifestation of sporotrichosis

PubMed Central

Freitas, Dayvison Francis Saraiva; Lima, Iluska Augusta Rocha; Curi, Carolina Lemos; Jordão, Livia; Zancopé-Oliveira, Rosely Maria; do Valle, Antonio Carlos Francesconi; Galhardo, Maria Clara Gutierrez; Curi, Andre Luiz Land

2013-01-01

Sporotrichosis associated with exposure to domestic cats is hyperendemic in Rio de Janeiro, Brazil. A review of the clinical records at our institute revealed four patients with clinical signs of dacryocystitis and a positive conjunctival culture for Sporothrix who were diagnosed with Sporothrix dacryocystitis. Three patients were children (< 13 years of age) and one patient was an adult. Two patients reported contact with a cat that had sporotrichosis. Dacryocystitis was associated with nodular, ulcerated lesions on the face of one patient and with granulomatous conjunctivitis in two patients; however, this condition manifested as an isolated disease in another patient. All of the patients were cured of the fungal infections, but three patients had chronic dacryocystitis and one patient developed a cutaneous fistula. Sporotrichosis is usually a benign disease, but may cause severe complications when the eye and the adnexa are affected. Physicians, especially ophthalmologists in endemic areas, should be aware of the ophthalmological manifestations and complications of sporotrichosis. PMID:24810176

Acute dacryocystitis: another clinical manifestation of sporotrichosis.

PubMed

Freitas, Dayvison Francis Saraiva; Lima, Iluska Augusta Rocha; Curi, Carolina Lemos; Jordão, Livia; Zancopé-Oliveira, Rosely Maria; Valle, Antonio Carlos Francesconi do; Galhardo, Maria Clara Gutierrez; Curi, Andre Luiz Land

2014-04-01

Sporotrichosis associated with exposure to domestic cats is hyperendemic in Rio de Janeiro, Brazil. A review of the clinical records at our institute revealed four patients with clinical signs of dacryocystitis and a positive conjunctival culture for Sporothrix who were diagnosed with Sporothrix dacryocystitis. Three patients were children (< 13 years of age) and one patient was an adult. Two patients reported contact with a cat that had sporotrichosis. Dacryocystitis was associated with nodular, ulcerated lesions on the face of one patient and with granulomatous conjunctivitis in two patients; however, this condition manifested as an isolated disease in another patient. All of the patients were cured of the fungal infections, but three patients had chronic dacryocystitis and one patient developed a cutaneous fistula. Sporotrichosis is usually a benign disease, but may cause severe complications when the eye and the adnexa are affected. Physicians, especially ophthalmologists in endemic areas, should be aware of the ophthalmological manifestations and complications of sporotrichosis.

Mast cell heterogeneity underlies different manifestations of food allergy in mice

PubMed Central

Benedé, Sara

2018-01-01

Food can trigger a diverse array of symptoms in food allergic individuals from isolated local symptoms affecting skin or gut to multi-system severe reactions (systemic anaphylaxis). Although we know that gastrointestinal and systemic manifestations of food allergy are mediated by tissue mast cells (MCs), it is not clear why allergen exposure by the oral route can result in such distinct clinical manifestations. Our aim was to assess the contribution of mast cell subsets to different manifestations of food allergy. We used two common models of IgE-mediated food allergy, one resulting in systemic anaphylaxis and the other resulting in acute gastrointestinal symptoms, to study the immune basis of allergic reactions. We used responders and non-responders in each model system, as well as naïve controls to identify the association of mast cell activation with clinical reactivity rather than sensitization. Systemic anaphylaxis was uniquely associated with activation of connective tissue mast cells (identified by release of mouse mast cell protease (MMCP) -7 into the serum) and release of histamine, while activation of mucosal mast cells (identified by release of MMCP-1 in the serum) did not correlate with symptoms. Gastrointestinal manifestations of food allergy were associated with an increase of MMCP-1-expressing mast cells in the intestine, and evidence of both mucosal and connective tissue mast cell activation. The data presented in this paper demonstrates that mast cell heterogeneity is an important contributor to manifestations of food allergy, and identifies the connective tissue mast cell subset as key in the development of severe systemic anaphylaxis. PMID:29370173

75 FR 60772 - Agency Information Collection Activities: Transportation Entry and Manifest of Goods Subject to...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-01

... Activities: Transportation Entry and Manifest of Goods Subject to CBP Inspection and Permit AGENCY: U.S... the Paperwork Reduction Act: Transportation Entry and Manifest of Goods Subject to CBP Inspection and... techniques or other forms of information. Title: Transportation Entry and Manifest of Goods Subject to CBP...

[Psychiatric manifestations by prions. A narrative review].

PubMed

Carrillo Robles, Daniel; García Maldonado, Gerardo

2016-01-01

Prion diseases are a group of rare and rapidly progressive neurodegenerative conditions that may cause neuropsychiatric symptoms. This group of diseases has been described since the 18(th) century, but they were recognized decades later, when it became clear that the humans were affected by infected animals. There was controversy when the problem was attributed to a single protein with infective capacity. The common pathological process is characterized by the conversion of the normal cellular prion protein into an abnormal form. In humans, the illness has been classified as idiopathic, inherited and acquired through exposure to exogenous material containing abnormal prions. The most prominent neurological manifestation of prion diseases is the emergence of a rapidly progressive dementia, mioclonus associated with cerebellar ataxia and also extra pyramidal symptoms. Psychiatric symptoms occur in early stages of the illness and can contribute to timely diagnosis of this syndrome. Psychiatric symptoms have traditionally been grouped in three categories: affective symptoms, impaired motor function and psychotic symptoms. Such events usually occur during the prodromal period prior to the neurological manifestations and consists in the presence of social isolation, onset of delusions, irritability/aggression, visual hallucinations, anxiety and depression, and less frequent first-rank symptoms among others. Definite diagnosis requires post mortem examination. The possibility that a large number of cases may occur in the next years or that many cases have not been considered with this diagnosis is a fact. In our opinion, psychiatrists should be aware of symptoms of this disease. The main objective of this research consisted of assessing the correlation between this disturbance and neuro-psychiatric symptoms and particularly if this psychiatric manifestations integrate a clinical picture suggestive for the diagnosis of these diseases, but firstly reviewed taxonomic

Cutaneous manifestations of the subtypes of polycystic ovary syndrome in Korean patients.

PubMed

Hong, J S; Kwon, H H; Park, S Y; Jung, J Y; Yoon, J Y; Min, S; Choi, Y M; Suh, D H

2015-01-01

Polycystic ovary syndrome (PCOS) is a common endocrinological disorder in women of childbearing-age. Although PCOS has common dermatological manifestations, including hirsutism, acne and androgenetic alopecia, little is known about the dermatological characteristics of PCOS patients in Asia. The goal of this study is to elucidate the dermatological characteristics and metabolic and hormonal parameters of Korean PCOS patients classified by the three ASRM/ESHERE criteria. We investigated 40 untreated PCOS patients who were newly diagnosed in the Department of Obstetrics & Gynecology of Seoul National University Hospital. Patients were classified according to the presence of irregular menstruation (IM), polycystic ovary morphology (PCOM) and hyperandrogenism (HA). Acne specific questionnaire, physical examination, and blood sampling were thoroughly conducted. Twenty four patients (60.0%) met the criteria for the IM/HA/PCOM group and sixteen (40.0%) belonged to the IM/PCOM group. Acne was the most commonly observed dermatological manifestation (95.0%) followed by hirsutism (60.0%), seoborrhea (47.5%), acanthosis nigricans (20.0%) and androgenetic alopecia (12.5%). Hirsutism was more frequently observed in the IM/HA/PCOM group; the prevalence of other cutaneous manifestations did not differ significantly. Acne was most often observed on the face and most acne lesions were distributed on the forehead and cheek. Serum dehydroepiandrosterone sulphate level was higher in IM/HA/PCOM group, while serum cholesterol and high density lipoprotein concentrations were higher in the IM/PCOM group. We described several dermatological manifestations and serum hormonal and metabolic parameters in Korean PCOS patients. Cutaneous manifestations might be the first signs of PCOS; therefore, dermatologists should be more aware of cutaneous manifestations of various ethnicities. © 2014 European Academy of Dermatology and Venereology.

Beneficial Effects of the Amino Acid Glycine.

PubMed

Pérez-Torres, Israel; Zuniga-Munoz, Alejandra María; Guarner-Lans, Veronica

2017-01-01

Glycine is the smallest non-essential, neutral and metabolically inert amino acid, with a carbon atom bound to two hydrogen atoms, and to an amino and a carboxyl group. This amino acid is an essential substrate for the synthesis of several biologically important biomolecules and compounds. It participates in the synthesis of proteins, of the tripeptide glutathione and in detoxification reactions. It has a broad spectrum of anti-inflammatory, cytoprotective and immunomodulatory properties. To exert its actions, glycine binds to different receptors. The GlyR anion channel is the most studied receptor for glycine. However, there are GlyR-independent mechanisms for glycine cytoprotection and other possible binding molecules of glycine are the NMDA receptor and receptors GlyT1 and GlyT2. Although, in humans, the normal serum level of glycine is approximately 300 μM, increasing glycine intake can lead to blood levels of more than 900 μM that increase its benefic actions without having harmful side effects. The herbal pesticide glyphosate might disrupt glycine homeostasis. Many in vitro studies involving different cell types have demonstrated beneficial effects of the addition of glycine. Glycine also improved conditions of isolated perfused or stored organs. In vivo studies in experimental animals have also tested glycine as a protector molecule and some studies on the beneficial effects of glycine after its clinical application have been done. Although at high-doses, glycine may cause toxic effects, further studies are needed to investigate the safe range of usage of this aminoacid and to test the diverse routes of administration.

Electrolyte disorders with platinum-based chemotherapy: mechanisms, manifestations and management.

PubMed

Oronsky, Bryan; Caroen, Scott; Oronsky, Arnold; Dobalian, Vaughn E; Oronsky, Neil; Lybeck, Michelle; Reid, Tony R; Carter, Corey A

2017-11-01

Platinum chemotherapy, particularly cisplatin, is commonly associated with electrolyte imbalances, including hypomagnesemia, hypokalemia, hypophosphatemia, hypocalcemia and hyponatremia. The corpus of literature on these dyselectrolytemias is large; the objective of this review is to synthesize the literature and summarize the mechanisms responsible for these particular electrolyte disturbances in the context of platinum-based treatment as well as to present the clinical manifestations and current management strategies for oncologists and primary care physicians, since the latter are increasingly called on to provide care for cancer patients with medical comorbidities. Correct diagnosis and effective treatment are essential to improved patient outcomes.

Elevation of serum N-terminal pro-brain natriuretic peptide after exercise is an index of myocardial damage or a cytoprotective reflection?

PubMed

Faviou, E; Zachari, A; Nounopoulos, C; Agrafiotis, E; Vourli, G; Dionyssiou-Asteriou, A

2008-03-01

Recent investigations have suggested the occurrence of transient cardiac dysfunction and reversible myocardial injury in healthy individuals after heavy exercise. Our purpose was to examine if the release of N-terminal pro-brain natriuretic peptide (NT-proBNP) after intense exercise in obviously healthy participants may have cytoprotective and growth-regulating effects or may result from myocardial dysfunction/damage with changes in cTnT as a marker for myocardial cell necrosis during exercise. In 43 highly-trained male athletes <35 years old, who were examined immediately after exercising as well as 2 days later, 21 age-matched male patients classified as stage-B according to ACC/AHA guidelines and 35 healthy age-matched males, we evaluated NT-proBNP and 3rd generation's cTnT by electrochemiluminescence immunoassay. All participants underwent a detailed cardiac protocol including echocardiography and electrocardiogram (ECG). In athletes, cTnT consistently remained <0.01 mg/L after exercising as well as after 2 days. NTproBNP immediately after exercising was 58.27+/-19.48 ng/L, without reaching pathological levels, decreasing 2 days later to 22.93+/-10.22 ng/L. Our patients maintained high levels of NTproBNP, as much as a six-fold increase with reference to the levels of our study's control group and with cTnT <0.01 mg/L. In the control group, cTnT and NTproBNP levels were statistically similar with those of the athletes 2 days after exercising. NT-proBNP as a biological marker can reliably discriminate pathological from physiological cardiac hypertrophy. A normal plasma concentration of NT-proBNP in consecutive routine check-up, before and after exercise, could minimize the possibility of cardiac dysfunction, whereas persistent elevated plasma concentrations warrant further cardiological evaluation.

Bolus oral glutamine protects rats against CPT-11-induced diarrhea and differentially activates cytoprotective mechanisms in host intestine but not tumor.

PubMed

Xue, Hongyu; Sawyer, Michael B; Field, Catherine J; Dieleman, Levinus A; Murray, David; Baracos, Vickie E

2008-04-01

Dietary glutamine has been suggested to preserve structural and functional integrity of the gut and high dose bolus glutamine has been hypothesized to protect against potentially fatal endotoxic shock, hyperthermic stress, and side effects of chemotherapy. In this study, we aimed to relate the ability of high dose oral bolus glutamine to mitigate the severe diarrhea induced by 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11) chemotherapy to specific cytoprotective mechanisms [heat shock response, glutathione (GSH)] in gut and tumor tissues. Female rats bearing Ward colon tumor received CPT-11 (125 mg x kg(-1) x d(-1)x 3 d) with or without an oral glutamine bolus (0.75 g/kg) administered 30 min prior to each CPT-11 dose. Glutamine reduced incidence and severity of late-onset diarrhea following CPT-11 treatment (P < 0.05) and was associated with potentially beneficial and protective responses in the colon: 1) a 3.1- to 7.2-fold increase of heat shock protein (Hsp)25,-70, and -90alpha (P < 0.05); 2) increased reduced GSH (rGSH):oxidized GSH ratio (P < 0.05); 3) prevention of upregulated activity of a key bacterial enzyme (beta-glucuronidase) in the cecal content that mediates CPT-11 intestinal toxicity (P < 0.05); and 4) increased proportions of CD3+CD8+ lymphocytes and memory CD8+ subset in mesenteric lymph nodes following CPT-11 therapy. By contrast, glutamine treatment did not alter CPT-11's antitumor activity, the amino acid concentrations, Hsp expression, or the ratio of rGSH:oxidized GSH in the tumor. Our data demonstrate a striking dichotomy in the response of tumor and host to oral glutamine administration, concurring with the concept that this nutrient may favorably alter the balance between the host and tumor.

40 CFR 262.54 - Special manifest requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Section 262.54 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS APPLICABLE TO GENERATORS OF HAZARDOUS WASTE Exports of Hazardous Waste § 262.54 Special... certification set forth in Item 16 of the Uniform Hazardous Waste Manifest Form: “and conforms to the terms of...

Dyslexia in Regular Orthographies: Manifestation and Causation

ERIC Educational Resources Information Center

Wimmer, Heinz; Schurz, Matthias

2010-01-01

This article summarizes our research on the manifestation of dyslexia in German and on cognitive deficits, which may account for the severe reading speed deficit and the poor orthographic spelling performance that characterize dyslexia in regular orthographies. An only limited causal role of phonological deficits (phonological awareness,…

Direct medical costs associated with the extrahepatic manifestations of hepatitis C virus infection in France.

PubMed

Cacoub, P; Vautier, M; Desbois, A C; Saadoun, D; Younossi, Z

2018-01-01

The economic impact of extrahepatic manifestations of hepatitis C virus (HCV) infection remains unknown for France. To estimate the prevalence of extrahepatic manifestations of HCV and the direct medical costs associated with them. Estimates of 13 extrahepatic manifestations prevalence were obtained from (1) a retrospective data analysis of HCV-infected patients in a specialised centre and the baseline prevalence in the general French population and (2) an international systematic review. Per-patient-per-year costs to treat these manifestations were obtained from the literature, national databases or expert opinion. The impact of achieving HCV cure after anti-viral therapy was applied to the French healthcare costs. Using approach (1), increased prevalence rates in HCV patients compared to the general population were observed for most extrahepatic manifestations. The mean per-patient-per-year cost of these manifestations in the tertiary centre was 3296 € [95% CI 1829; 5540]. In France, HCV-extrahepatic manifestations amounted to a total cost of 215 million (M) € per year [144; 299]. Using approach (2), the mean per-patient-per-year cost was estimated to be 1117 €. The estimated total cost reduction in France associated with HCV cure was 13.9 M€ for diabetes, 8.6 M€ for cryoglobulinemia vasculitis, 6.7 M€ for myocardial infarction, 2.4 M€ for end-stage renal disease and 1.4 M€ for stroke. Extrahepatic manifestations of HCV infection substantially add to the overall economic burden of the disease in France. HCV cure after anti-viral therapy is expected to significantly reduce the total costs of managing these manifestations in France. © 2017 John Wiley & Sons Ltd.

Oral Manifestations and Molecular Basis of Oral Genodermatoses: A Review

PubMed Central

Shilpasree, A.S.; Chaudhary, Meenakshi

2016-01-01

Genodermatoses refers to group of inherited monogenic disorders with skin manifestations. Many of these disorders are rare and also have oral manifestations, called oral genodermatoses. This article provides a focused review of molecular basis of important genodermatoses that affects the oral cavity and also have prominent associated dermatologic features. In several conditions discussed here, the oral findings are distinct and may provide the first clue of an underlying genetic diagnosis. The article also emphasises on the prenatal diagnosis, genetic counselling and the treatment oral genodermatoses. PMID:27437377

Manifesting the Quantum World

NASA Astrophysics Data System (ADS)

Mohrhoff, Ulrich

2014-06-01

In resisting attempts to explain the unity of a whole in terms of a multiplicity of interacting parts, quantum mechanics calls for an explanatory concept that proceeds in the opposite direction: from unity to multiplicity. Being part of the Scientific Image of the world, the theory concerns the process by which (the physical aspect of) what Sellars called the Manifest Image of the world comes into being. This process consists in the progressive differentiation of an intrinsically undifferentiated entity. By entering into reflexive spatial relations, this entity gives rise to (i) what looks like a multiplicity of relata if the reflexive quality of the relations is not taken into account, and (ii) what looks like a substantial expanse if the spatial quality of the relations is reified. If there is a distinctly quantum domain, it is a non-spatial and non-temporal dimension across which the transition from the unity of this entity to the multiplicity of the world takes place. Instead of being constituents of the physical world, subatomic particles, atoms, and molecules are instrumental in its manifestation. These conclusions are based on the following interpretive principle and its more direct consequences: whenever the calculation of probabilities calls for the addition of amplitudes, the distinctions we make between the alternatives lack objective reality. Applied to alternatives involving distinctions between regions of space, this principle implies that, owing to the indefiniteness of positions, the spatiotemporal differentiation of the physical world is incomplete: the existence of a real-valued spatiotemporal background is an unrealistic idealization. This guarantees the existence of observables whose values are real per se, as against "real by virtue of being indicated by the values of observables that are real per se." Applied to alternatives involving distinctions between things, it implies that, intrinsically, all fundamental particles are numerically

In vitro evaluation of antioxidants of fruit extract of Momordica charantia L. on fibroblasts and keratinocytes.

PubMed

Kumar, Ramadhar; Balaji, S; Sripriya, R; Nithya, N; Uma, T S; Sehgal, P K

2010-02-10

The antioxidant activity of the total aqueous extract (TAE) and total phenolic extract (TPE) of Momordica charantia fruits was assayed by radical-scavenging methods and cytoprotective effects on hydrogen peroxide (H(2)O(2))- and hypoxanthin-xanthin oxidase (HX-XO)-induced damage to rat cardiac fibroblasts (RCFs), NIH 3T3, and keratinocyte (A431). Cell viability was monitored by a 3-[4,5-dimethyltriazol-2-yl]-2,5-diphenyltretrazolium (MTT) assay. For fibroblasts, TPE at 200 and 300 microg/mL showed maximum and consistent cytoprotection against oxidants. The extract at 50 microg/mL also had significant and slightly protective effects on fibroblasts against H(2)O(2)- and HX-XO-induced damage, respectively. RCF was more tolerant toward the damage. For keratinocytes, a dose-dependent relationship of oxidant toxicity was only seen with H(2)O(2) but the protective action of the extract correlated with oxidant dosage. At 200 and 300 microg/mL TPE, cytoprotection was dose-dependent against oxidants. Extracts had no effect on HX-XO toxicity at 50 microg/mL. Pretreatment with both the extracts did not show any cytoprotection.

19 CFR 103.31 - Information on vessel manifests and summary statistical reports.

Code of Federal Regulations, 2013 CFR

2013-04-01

... shall thereafter be denied access to such papers. (e) Availability of manifest data on CD-ROMS—(1... members of the public on CD-ROMS. This data, compiled daily, will contain all manifest transactions made... confidential treatment in accordance with paragraph (d) of this section will not be included on the CD-ROMS...

19 CFR 103.31 - Information on vessel manifests and summary statistical reports.

Code of Federal Regulations, 2012 CFR

2012-04-01

... shall thereafter be denied access to such papers. (e) Availability of manifest data on CD-ROMS—(1... members of the public on CD-ROMS. This data, compiled daily, will contain all manifest transactions made... confidential treatment in accordance with paragraph (d) of this section will not be included on the CD-ROMS...

Manifestations of Gorlin-Goltz syndrome.

PubMed

Larsen, Anne Kristine; Mikkelsen, Dorthe Bisgaard; Hertz, Jens Michael; Bygum, Anette

2014-05-01

Gorlin-Goltz syndrome is an uncommon hereditary condition caused by mutations in the PTCH1 gene causing a wide range of developmental abnormalities. Multiple basal cell carcinomas, palmoplantar pits and jaw cysts are cardinal features. Many clinicians are unfamiliar with the different manifestations and the fact that patients are especially sensitive to ionizing radiation. This was a retrospective analysis of patients with Gorlin-Goltz syndrome seen at the Department of Dermatology and Allergy Centre or at Department of Plastic Surgery, Odense University Hospital, Denmark, in the period from 1994 to 2013. A total of 17 patients from eight families fulfilled the diagnostic criteria. In all, 14 patients had basal cell carcinomas, 12 patients had jaw cysts and ten patients had calcification of the falx cerebri. Other clinical features were frontal bossing, kyphoscoliosis, rib anomalies, coalitio, cleft lip/palate, eye anomalies, milia and syndactyly. In one family, medulloblastoma and astrocytoma occurred. Traditional treatment principles of basal cell carcinomas were used including radiotherapy performed in six patients. PTCH1 mutations were identified in five families and none of these mutations had previously been described. The patient cohort illustrates classic and rare disease manifestations. It is necessary to remind clinicians that radiation therapy in Gorlin-Goltz syndrome is relatively contraindicated. Today, mutation analysis can be used for confirmation of the diagnosis and for predictive genetic testing. Patients should be offered genetic counselling and life-long surveillance. not relevant. not relevant.

[Acute encephalitis. Neuropsychiatric manifestations as expression of influenza virus infection].

PubMed

Moreno-Flagge, Noris; Bayard, Vicente; Quirós, Evelia; Alonso, Tomás

2009-01-01

The aim is to review the encephalitis in infants and adolescents as well as its etiology, clinical manifestation, epidemiology, physiopathology, diagnostic methods and treatment, and the neuropsyquiatric signs appearing an influenza epidemy. Encephalitis is an inflammation of the central nervous system (CNS) which involves the brain. The clinical manifestations usually are: headache, fever and confusional stage. It could also be manifested as seizures, personality changes, or psiqyiatric symptoms. The clinical manifestations are related to the virus and the cell type affected in the brain. A meningitis or encephalopathy need to be ruled out. It could be present as an epidemic or isolated form, beeing this the most frequent form. It could be produced by a great variety of infections agents including virus, bacterias, fungal and parasitic. Viral causes are herpesvirus, arbovirus, rabies and enterovirus. Bacterias such as Borrelia burgdorferi, Rickettsia and Mycoplasma neumoniae. Some fungal causes are: Coccidioides immitis and Histoplasma capsulatum. More than 100 agents are related to encephalitis. The diagnosis of encephalitis is a challenge for the clinician and its infectious etiology is clear in only 40 to 70% of all cases. The diagnosis of encephalitis can be established with absolute certainty only by the microscopic examination of brain tissue. Epidemiology is related to age of the patients, geographic area, season, weather or the host immune system. Early intervention can reduce the mortality rate and sequels. We describe four patients with encephalitis and neuropsychiatric symptoms during an influenza epidemic.

Aging-Related Systemic Manifestations in COPD Patients and Cigarette Smokers

PubMed Central

Boyer, Laurent; Marcos, Elisabeth; Margarit, Laurent; Le Corvoisier, Philippe; Vervoitte, Laetitia; Hamidou, Leila; Frih, Lamia; Audureau, Etienne; Covali-Noroc, Ala; Andujar, Pascal; Saakashvili, Zakaria; Lino, Anne; Ghaleh, Bijan; Hue, Sophie; Derumeaux, Geneviève; Housset, Bruno; Dubois-Randé, Jean-Luc; Boczkowski, Jorge; Maitre, Bernard; Adnot, Serge

2015-01-01

Rationale Chronic obstructive pulmonary disease (COPD) is often associated with age-related systemic abnormalities that adversely affect the prognosis. Whether these manifestations are linked to the lung alterations or are independent complications of smoking remains unclear. Objectives To look for aging-related systemic manifestations and telomere shortening in COPD patients and smokers with minor lung destruction responsible for a decline in the diffusing capacity for carbon monoxide (DLCO) corrected for alveolar volume (KCO). Methods Cross-sectional study in 301 individuals (100 with COPD, 100 smokers without COPD, and 101 nonsmokers without COPD). Measurements and Main Results Compared to control smokers, patients with COPD had higher aortic pulse-wave velocity (PWV), lower bone mineral density (BMD) and appendicular skeletal muscle mass index (ASMMI), and shorter telomere length (TL). Insulin resistance (HOMA-IR) and glomerular filtration rate (GFR) were similar between control smokers and COPD patients. Smokers did not differ from nonsmokers for any of these parameters. However, smokers with normal spirometry but low KCO had lower ASMMI values compared to those with normal KCO. Moreover, female smokers with low KCO, had lower BMD and shorter TL compared to those with normal KCO. Conclusions Aging-related abnormalities in patients with COPD are also found in smokers with minor lung dysfunction manifesting as a KCO decrease. Decreased KCO might be useful, particularly among women, for identifying smokers at high risk for aging-related systemic manifestations and telomere shortening. PMID:25785739

Neoliberalism, Curriculum Development and Manifestations of "Creativity"

ERIC Educational Resources Information Center

Hakala, Juha T.; Uusikylä, Kari; Järvinen, Esa-Matti

2015-01-01

There is a manifest tendency for national education policy to follow global economic trends. In many Western industrialized countries, this relationship has intensified or strengthened within the last decades. The strengthening of this relationship has been seen, among other things, as evidence of the growing power of neoliberal ideology. The…

Antimicrobial activity, acute toxicity and cytoprotective effect of Crassocephalum vitellinum (Benth.) S. Moore extract in a rat ethanol-HCl gastric ulcer model

PubMed Central

2014-01-01

Background A decoction of Crassocephallum vitellinum (Benth.) S. Moore (Asteraceae) is used in Kagera Region to treat peptic ulcers. This study seeks to evaluate an aqueous ethanol extract of aerial parts of the plant for safety and efficacy. Methods An 80% ethanolic extract of C. vitellinum at doses of 100, 200, 400 and 800 mg/kg body wt was evaluated for ability to protect Sprague Dawley rats from acidified ethanol gastric ulceration in comparison with 40 mg/kg body wt pantoprazole. The extract and its dichloromethane, ethyl acetate, and aqueous fractions were also evaluated for acute toxicity in mice, brine shrimp toxicity, and antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922), Salmonella typhi (NCTC 8385), Vibrio cholera (clinical isolate), and Streptococcus faecalis (clinical isolate). The groups of phytochemicals present in the extract were also determined. Results The ethanolic extract of C. vitellinum dose-dependently protected rat gastric mucosa against ethanol/HCl insult to a maximum of 88.3% at 800 mg/kg body wt, affording the same level of protection as by 40 mg/kg body wt pantoprazole. The extract also exhibited weak antibacterial activity against S. typhi and E. coli, while its ethyl acetate, dichloromethane and aqueous fractions showed weak activity against K. pneumonia, S.typhi, E. coli and V. cholera. The extract was non-toxic to mice up to 5000 mg/kg body wt, and the total extract (LC50 = 37.49 μg/ml) and the aqueous (LC50 = 87.92 μg/ml), ethyl acetate (LC50 = 119.45 μg/ml) and dichloromethane fractions (88.79 μg/ml) showed low toxicity against brine shrimps. Phytochemical screening showed that the extract contains tannins, saponins, flavonoids, and terpenoids. Conclusion The results support the claims by traditional healers that a decoction of C.vitellinum has antiulcer activity. The mechanism of cytoprotection is yet to be determined but the phenolic compounds present in the

Cutaneous manifestations of phosphate solution extravasation.

PubMed

Verykiou, S; Aljefri, K; Gopee, H; Taheri, L; Charlton, F; Langtry, J A; Blasdale, C

2018-01-01

Extravasation injuries are common in patients receiving multiple intravenous infusions. Although such injuries are closely associated with the infusion of cytotoxic chemotherapy, they have also been been associated with extravasation of noncytotoxic drugs. Extravasation injuries can lead to skin ulceration and nerve and tendon damage, and therefore to permanent disability. We report three cases of phosphate solution extravasation leading to unusual cutaneous manifestations. © 2017 British Association of Dermatologists.

Psychiatric manifestations of 22q11.2 deletion syndrome: a literature review.

PubMed

Bertrán, M; Tagle, F P; Irarrázaval, M

2018-03-01

The 22q11.2 deletion syndrome is a genetic disorder with variable clinical manifestations. It affects one out of 5950 neonates and has an autosomal dominant inheritance pattern. The aim of this article is to review its psychiatric manifestations and any underlying genetic alterations. We reviewed the scientific literature available as of October 2014 in the LILACS and Medline databases. Sixty per cent of these patients fulfilled diagnostic criteria for a mental disorder at some point in their lives, referring to psychotic disorders, attention deficit hyperactivity disorder, mood disorders, anxiety disorders, and autism spectrum disorders. Specific genes, such as COMT and PRODH, have been linked to these psychiatric manifestations. It is necessary to raise awareness among all health care professionals so that they understand the relevance of these manifestations, are able to anticipate them, and can provide appropriate information to patients and family members. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Manifest: A computer program for 2-D flow modeling in Stirling machines

NASA Technical Reports Server (NTRS)

Gedeon, David

1989-01-01

A computer program named Manifest is discussed. Manifest is a program one might want to use to model the fluid dynamics in the manifolds commonly found between the heat exchangers and regenerators of Stirling machines; but not just in the manifolds - in the regenerators as well. And in all sorts of other places too, such as: in heaters or coolers, or perhaps even in cylinder spaces. There are probably nonStirling uses for Manifest also. In broad strokes, Manifest will: (1) model oscillating internal compressible laminar fluid flow in a wide range of two-dimensional regions, either filled with porous materials or empty; (2) present a graphics-based user-friendly interface, allowing easy selection and modification of region shape and boundary condition specification; (3) run on a personal computer, or optionally (in the case of its number-crunching module) on a supercomputer; and (4) allow interactive examination of the solution output so the user can view vector plots of flow velocity, contour plots of pressure and temperature at various locations and tabulate energy-related integrals of interest.

Atypical manifestations of Epstein-Barr virus in children: a diagnostic challenge.

PubMed

Bolis, Vasileios; Karadedos, Christos; Chiotis, Ioannis; Chaliasos, Nikolaos; Tsabouri, Sophia

2016-01-01

Clarify the frequency and the pathophysiological mechanisms of the rare manifestations of Epstein-Barr virus infection. Original research studies published in English between 1985 and 2015 were selected through a computer-assisted literature search (PubMed and Scopus). Computer searches used combinations of key words relating to "EBV infections" and "atypical manifestation." Epstein-Barr virus is a herpes virus responsible for a lifelong latent infection in almost every adult. The primary infection concerns mostly children and presents with the clinical syndrome of infectious mononucleosis. However, Epstein-Barr virus infection may exhibit numerous rare, atypical and threatening manifestations. It may cause secondary infections and various complications of the respiratory, cardiovascular, genitourinary, gastrointestinal, and nervous systems. Epstein-Barr virus also plays a significant role in pathogenesis of autoimmune diseases, allergies, and neoplasms, with Burkitt lymphoma as the main representative of the latter. The mechanisms of these manifestations are still unresolved. Therefore, the main suggestions are direct viral invasion and chronic immune response due to the reactivation of the latent state of the virus, or even various DNA mutations. Physicians should be cautious about uncommon presentations of the viral infection and consider EBV as a causative agent when they encounter similar clinical pictures. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Clofibrate prevents and reverses the hemodynamic manifestations of hyperthyroidism in rats.

PubMed

Rodríguez-Gómez, Isabel; Cruz, Antonio; Moreno, Juan Manuel; Soler, Agatángelo; Osuna, Antonio; Vargas, Félix

2008-03-01

This study analyzed the effects of the chronic administration of clofibrate, a peroxisome proliferator-activated receptor-alpha (PPARalpha) agonist, on the development and established hemodynamic, morphologic, metabolic, and renal manifestations of hyperthyroidism in rats. The prevention study used four groups of male Wistar rats: control, clofibrate (240 mg/kg/day by gavage), T(4)(75 microg thyroxine/rat/day s.c.), and T(4)+clofibrate. All treatments were maintained for 3 weeks. Body weight (BW), tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, temperature, SBP, pulse pressure (PP) and HR were recorded in conscious rats, and morphologic, metabolic, plasma, and renal variables were measured. The reversion study used two groups of rats, T(4)(treated for 6 weeks) and T(4)+clofibrate, measuring their hemodynamic variables and temperature for 3 weeks. T(4) increased BP, HR, PP, and temperature when compared with control rats. Clofibrate prevented and reversed the increase in SBP, HR, PP, and temperature produced by T(4) administration, reduced plasma thyroid hormone levels, and increased plasma thyroid-stimulating hormone values and phenol-uridine diphosphate-glucuronosyl-transferase (UGT) activity. However, clofibrate did not modify the cardiac or renal hypertrophy, polyphagia, polydipsia, or proteinuria of hyperthyroid rats. In normal rats, clofibrate treatment did not significantly change thyroid hormone levels, phenol-UGT activity, or any hemodynamic, morphologic, or renal variables. Chronic clofibrate treatment suppressed the hemodynamic manifestations and increased temperature of hyperthyroidism, an effect that can be produced by direct antithyroid effects. However, clofibrate administration did not modify the morphologic, metabolic, or renal alterations of hyperthyroid rats, indicating specificity in the antithyroid actions of clofibrate.

Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and vascular response.

PubMed

Sikiric, P; Seiwerth, S; Brcic, L; Blagaic, A B; Zoricic, I; Sever, M; Klicek, R; Radic, B; Keller, N; Sipos, K; Jakir, A; Udovicic, M; Tonkic, A; Kokic, N; Turkovic, B; Mise, S; Anic, T

2006-12-01

Gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419, safe in clinical trials for inflammatory bowel disease (PL 10, PLD 116, PLD 14736, Pliva, Croatia)) has a particular cytoprotective/adaptive cytoprotective activity. The cytoprotective/adaptive cytoprotection researches largely neglect that stomach distension could per se jeopardize the mucosal integrity, with constantly stretched mucosa and blood vessels, and sphincters more prone for reflux induction. After absolute alcohol instillation in fully distended rat stomach, gastric, esophageal and duodenal lesions occur. Throughout next 3 min, left gastric artery blood vessels clearly disappear at the serosal site, indicative for loss of vessels both integrity and function. Contrary, constant vessels presentation could predict the beneficial effect of applied agent. After pentadecapeptide BPC 157 instillation into the stomach the vessels presentation remains constant, and lesions of stomach, esophagus, and duodenum are inhibited. Standards (atropine, ranitidine, omeprazole) could only slightly improve the vessels presentation compared to control values, and they have only a partial effect on the lesions. In this review we emphasize BPC 157 unusual stability, and some of its important effects: effectiveness against various lesions in gastrointestinal tract, on nitric oxide (NO)-system, and NO-agents effects, on somatosensory neurons, salivary glands function, recovery of AMP-ADP-ATP system, endothelium protection, effect on endothelin, and on angiogenesis promotion. It also antagonizes other alcohol effects, including acute and chronic intoxication. Given peripherally, it counteracts the consequence of central dopamine system disturbances (receptor blockade), and induces serotonin release in substantia nigra. Therapeutic potential of BPC 157 as a cytoprotective agent is also seen in its capability to heal various wounds. Given directly into the stomach, BPC 157 instantly recovers disturbed lower esophageal

40 CFR 263.20 - The manifest system.

Code of Federal Regulations, 2010 CFR

2010-07-01

... person if he knows the shipment does not conform to the EPA Acknowledgment of Consent; and unless, in... without a tracking document that includes all information required by 40 CFR 262.84. (3) Compliance Date... designated facility on either the manifest or the shipping paper; and (4) The person delivering the hazardous...

[Clinical, endoscopic and morphological manifestations of oesophageal lesion in systemic scleroderma].

PubMed

Karateev, A E; Movsiian, A E; Anan'eva, M M; Radenska-Lopovok, S G

2014-01-01

Oesophageal lesion is the commonest visceral manifestation of systemic scleroderma (SSD) affecting the quality of life and fraught with serious complications. The aim of this study was to evaluate clinical, endoscopic andmorphological manifestations of oesophageal lesion in systemic scleroderma and its relationships with other clinical symptoms and pharmacotherapy of the disease. 479 patients with SSD (93.7% women, 6.3% men, mean age 48.7 +/- 19.2 yr). All of them underwent EGDS in 2005-2010. 123 patients were examined for the detection of Barrett's oesophagus (BO), total screening regardless of complaints was conducted in 2010. Control group included 1018 age and sex-matched patients with RA who underwent EGDS in 2008-2009. Oesophageal lesions occurred much more frequently in SSD than in RA. Oesophageal symptoms were documented in 70.0 and 29.9% cases, non-erosive oesopahgitis in 28.8 and 1.5%, erosive esophagitis in 22.5 and 2.2% ulcers in 0.8 and 0% (p < 0.001). BO manifested as intestinal metaplasia (histological study of mucosal biopsy) was found in 30 SSD patients (4.2%). Screening revealed BO in 8.9% of the patients. The development of erosive oesophagitis was unrelated to the age of the patients, duration of the disease and its form (localized or diffusive), lung pathology or Sjogren's syndrome. Cytotoxic medicines significantly increased the frequency of erosive oesophagitis, it tended to increase under effect of NSAID and low doses of aspirin. Long-term intake of PPI did not reduce the risk of oesophagitis and BO. Half of the patients with SSD have oesophagitis. Over 20% of them suffer its complications (erosion and ulcers) and 9% have BO. All such patients need endoscopic study ofoesophagus regardless of clinical symptoms.

[Gorlin-Goltz syndrome: manifestations in an elderly patient].

PubMed

Kos, S; Feil, B; Radü, E W

2007-10-31

Gorlin-Goltz syndrome is a rare inherited genodermatosis with an autosomal dominant trait. We hereby present a case of a 69 year old patient with known Gorlin-Goltz syndrome to emphasize the peculiar syndrome manifestations in the elderly.

Topical Rapamycin Therapy to Alleviate Cutaneous Manifestations of Tuberous Sclerosis Complex

DTIC Science & Technology

2015-05-01

AD Award Number: W81XWH-11-1-0240 Title: Topical Rapamycin Therapy to Alleviate Cutaneous Manifestations of Tuberous Sclerosis Complex Principal...1Sep2011 - 28Feb2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Topical Rapamycin Therapy to Alleviate Cutaneous Manifestations of Tuberous Sclerosis...organ systems. The TSC1 and TSC2 gene products are involved in cell signaling; in particular they are involved in the mammalian target of rapamycin

Neurovascular manifestations of connective-tissue diseases: A review

PubMed Central

Kim, Sarasa T; Lanzino, Giuseppe; Kallmes, David F

2016-01-01

Patients with connective tissue diseases are thought to be at a higher risk for a number of cerebrovascular diseases such as intracranial aneurysms, dissections, and acute ischemic strokes. In this report, we aim to understand the prevalence and occurrences of such neurovascular manifestations in four heritable connective tissue disorders: Marfan syndrome, Ehlers-Danlos syndrome, Neurofibromatosis Type 1, and Loeys-Dietz syndrome. We discuss the fact that although there are various case studies reporting neurovascular findings in these connective tissue diseases, there is a general lack of case-control and prospective studies investigating the true prevalence of these findings in these patient populations. Furthermore, the differences observed in the manifestations and histology of such disease pathologies encourages future multi-center registries and studies in better characterizing the pathophysiology, prevalence, and ideal treatment options of neurovascular lesions in patents with connective tissue diseases. PMID:27511817

Imaging of musculoskeletal manifestations in sickle cell disease patients.

PubMed

Kosaraju, Vijaya; Harwani, Alok; Partovi, Sasan; Bhojwani, Nicholas; Garg, Vasant; Ayyappan, Sabarish; Kosmas, Christos; Robbin, Mark

2017-05-01

Sickle cell disease (SCD) is a hereditary red cell disorder with clinical manifestations secondary to sickling or crescent-shaped distortion of the red blood cells. Major clinical manifestations of SCD include haemolytic anaemia and vaso-occlusive phenomena resulting in ischaemic tissue injury and organ damage. Chronic sequelae of the anaemia and vaso-occlusive processes involving the musculoskeletal system include complications related to extramedullary haematopoiesis, osteonecrosis, myonecrosis and osteomyelitis. Sickle cell bone disease is one of the commonest clinical presentations. Awareness and knowledge of the imaging features related to these complications are essential for early diagnosis and prompt management. In this article, the pathophysiology and key imaging findings related to these complications are reviewed.

Clinical Manifestations and Outcomes of West Nile Virus Infection

PubMed Central

Sejvar, James J.

2014-01-01

Since the emergence of West Nile virus (WNV) in North America in 1999, understanding of the clinical features, spectrum of illness and eventual functional outcomes of human illness has increased tremendously. Most human infections with WNV remain clinically silent. Among those persons developing symptomatic illness, most develop a self-limited febrile illness. More severe illness with WNV (West Nile neuroinvasive disease, WNND) is manifested as meningitis, encephalitis or an acute anterior (polio) myelitis. These manifestations are generally more prevalent in older persons or those with immunosuppression. In the future, a more thorough understanding of the long-term physical, cognitive and functional outcomes of persons recovering from WNV illness will be important in understanding the overall illness burden. PMID:24509812

Hematologic manifestations of Helicobacter pylori infection

PubMed Central

Campuzano-Maya, Germán

2014-01-01

Helicobacter pylori (H. pylori) is the most common infection in humans, with a marked disparity between developed and developing countries. Although H. pylori infections are asymptomatic in most infected individuals, they are intimately related to malignant gastric conditions such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to benign diseases such as gastritis and duodenal and gastric peptic ulcers. Since it was learned that bacteria could colonize the gastric mucosa, there have been reports in the medical literature of over 50 extragastric manifestations involving a variety medical areas of specialization. These areas include cardiology, dermatology, endocrinology, gynecology and obstetrics, hematology, pneumology, odontology, ophthalmology, otorhinolaryngology and pediatrics, and they encompass conditions with a range of clear evidence between the H. pylori infection and development of the disease. This literature review covers extragastric manifestations of H. pylori infection in the hematology field. It focuses on conditions that are included in international consensus and management guides for H. pylori infection, specifically iron deficiency, vitamin B12 (cobalamin) deficiency, immune thrombocytopenia, and MALT lymphoma. In addition, there is discussion of other conditions that are not included in international consensus and management guides on H. pylori, including auto-immune neutropenia, antiphospholipid syndrome, plasma cell dyscrasias, and other hematologic diseases. PMID:25278680

Ionospheric manifestations of earthquakes and tsunamis in a dynamic atmosphere

NASA Astrophysics Data System (ADS)

Godin, Oleg A.; Zabotin, Nikolay A.; Zabotina, Liudmila

2015-04-01

Observations of the ionosphere provide a new, promising modality for characterizing large-scale physical processes that occur on land and in the ocean. There is a large and rapidly growing body of evidence that a number of natural hazards, including large earthquakes, strong tsunamis, and powerful tornadoes, have pronounced ionospheric manifestations, which are reliably detected by ground-based and satellite-borne instruments. As the focus shifts from detecting the ionospheric features associated with the natural hazards to characterizing the hazards for the purposes of improving early warning systems and contributing to disaster recovery, it becomes imperative to relate quantitatively characteristics of the observed ionospheric disturbances and the underlying natural hazard. The relation between perturbations at the ground level and their ionospheric manifestations is strongly affected by parameters of the intervening atmosphere. In this paper, we employ the ray theory to model propagation of acoustic-gravity waves in three-dimensionally inhomogeneous atmosphere. Huygens' wavefront-tracing and Hamiltonian ray-tracing algorithms are used to simulate propagation of body waves from an earthquake hypocenter through the earth's crust and ocean to the upper atmosphere. We quantify the influence of temperature stratification and winds, including their seasonal variability, and air viscosity and thermal conductivity on the geometry and amplitude of ionospheric disturbances that are generated by seismic surface waves and tsunamis. Modeling results are verified by comparing observations of the velocity fluctuations at altitudes of 150-160 km by a coastal Dynasonde HF radar system with theoretical predictions of ionospheric manifestations of background infragravity waves in the ocean. Dynasonde radar systems are shown to be a promising means for monitoring acoustic-gravity wave activity and observing ionospheric perturbations due to earthquakes and tsunamis. We will discuss

[Clinical analysis of cutaneous manifestations and related factors in patients with ulcerative colitis].

PubMed

Tian, Y; Li, J X; Wang, H H; Li, R Y; Liu, X G

2016-07-01

To investigate the cutaneous manifestations in patients with ulcerative colitis (UC) and related factors. Patients admitted to Department of Gastroenterology Peking University First Hospital from January 1994 to December 2014 and diagnosed as UC were retrospectively enrolled in this study. Skin disorders were confirmed by the dermatologists. Clinical data were collected and compared between patients with and without cutaneous manifestations. Among the total 373 UC patients, there were 34 cases (9.1%) with cutaneous manifestations, including 11 pyoderma gangrenosum, 8 erythema nodosum, 6 eczema, 3 psoriasis, 2 pemphigus, 1 granulomatous cheilitis, 1 ichthyosis, 1 acne rosacea, and 1 impetigo. The skin manifestations may occur after the diagnosis, simultaneously or even before the diagnosis of UC, which were 24, 7 and 3 patients respectively. The mean age in patients with skin lesions was (47.2±12.1) years, male to female ratio 0.79∶1. More patients with skin manifestations had severe activity of UC compared with non-skin group [50.0%(17/34) vs 25.1%(85/339), P=0.01]. In addition, the proportion of extensive colitis in skin lesion group was significantly higher than that in non-skin group [76.5%(26/34) vs 54.6%(185/339), P=0.04]. The cutaneous manifestations associated with UC are polymorphic, erythema nodosums and pyoderma gangrenosums are the most common skin lesions seen in UC patients. Skin lesions occur concurrently, pre or post the diagnosis of UC. Skin lesions in UC patients suggest more severe disease activity. Clinicians need to pay more attention to this group.

[Association between glutathione peroxidase levels and clinical manifestations of dengue].

PubMed

Rojas, Elsa Marina; Díaz-Quijano, Fredi Alexander; Coronel-Ruiz, Carolina; Martínez-Vega, Ruth Aralf; Rueda, Ernesto; Villar-Centeno, Luis Angel

2007-06-01

Glutathione peroxidase (GP) can be used as a marker of oxidative stress in infectious diseases. To evaluate the association between the levels of glutathione peroxidase (GP) and the manifestations and complications of dengue. Between April 2003 and December 2004, 161 patients with dengue were prospectively evaluated. In the first evaluation, within 48 and 96 hours of disease onset, a plasma sample was obtained to measure the GP levels. The association between GP levels, clinical manifestations and complications was evaluated during the follow up. Mean GP values were 1198 U/L (95% confidence interval 1089-1306). Values greater than 1200 U/L were associated with headache, arthralgias and increased heart rate. There was a negative association between GP levels and serum triglycerides. During follow up, patients with GP >1200 U/L had a higher frequency of spontaneous hemorrhages. In a logistic regression analysis arthralgias, fever and increased heart rate, were independently associated with levels >1200 U/L. GP levels was associated to some of the manifestations of dengue. This finding suggests that the intensity of oxidative stress can influence the clinical presentation of dengue.

Myoelectric manifestations of jaw elevator muscle fatigue and recovery in healthy and TMD subjects.

PubMed

Castroflorio, T; Falla, D; Tartaglia, G M; Sforza, C; Deregibus, A

2012-09-01

The effects of muscle pain and fatigue on the control of jaw elevator muscles are not well known. Furthermore, the myoelectric manifestations of fatigue and recovery from fatigue in the masticatory muscles are not reported in literature. The main aims of this study were (i) to evaluate the possible use of surface electromyography (sEMG) as an objective measure of fatigue of the jaw elevator muscles, (ii) to compare the myoelectric manifestations of fatigue in the temporalis anterior and masseter muscles bilaterally, (iii) to assess recovery of the investigated muscles after an endurance test and (iv) to compare fatigue and recovery of the jaw elevator muscles in healthy subjects and patients with muscle-related temporomandibular disorders (TMD). The study was performed on twenty healthy volunteers and eighteen patients with muscle-related TMD. An intra-oral compressive-force sensor was used to measure the voluntary contraction forces close to the intercuspal position and to provide visual feedback of submaximal forces to the subject. Surface EMG signals were recorded with linear electrode arrays during isometric contractions at 20%, 40%, 60% and 80% of the maximum voluntary contraction force, during an endurance test and during the recovery phase. The results showed that (i) the slope of the mean power spectral frequency (MNF) and the initial average rectified value (ARV) could be used to monitor fatigue of the jaw elevators, (ii) the temporalis anterior and masseter muscle show the same myoelectric manifestations of fatigue and recovery and (iii) the initial values of MNF and ARV were lower in patients with muscle-related TMD. The assessment of myoelectric manifestations of fatigue in the masticatory muscles may assist in the clinical assessment of TMDs. © 2012 Blackwell Publishing Ltd.

[Hereditary hemochromatosis: presenting manifestations and diagnostic delay].

PubMed

Gasser, B; Courtois, F; Hojjat-Assari, S; Sauleau, E A; Buffet, C; Brissot, P

2014-03-01

Hereditary hemochromatosis is characterized by an excessive absorption and progressive accumulation of iron in the liver, the pancreas, the heart, and the joints. Tiredness and joint manifestations occur usually before hepatopathy, diabetes or cardiopathy. Such common and unspecific symptoms seem to be largely unknown and important diagnostic delays have been reported. The aim of this study was to investigate the discovery circumstances and the diagnostic delay. A survey was carried out amongst French patients with C282Y homozygous hemochromatosis who were contacted through patients associations or blood centers. The questionnaire was answered by 374 patients. Mean age at diagnosis was 48.6±11.9years. In 53% of the cases, the serum level of ferritin was greater than 1000 μg/L. Diagnosis was based on family genetic survey (29%), or fortuitous analyses showing an abnormal serum ferritin (26%), or clinical manifestations (45%). Main complaints were joint pain, tiredness or liver disease. Only 2.1% consulted for diabetes, cardiopathy or changed complexion. Time to diagnosis was lower than 1 year for 98% of patients who presented with fatigue but from 1 to 15 years for 23.4% and 29% of patients who presented with arthropathy and hepatopathy, respectively. For 55% of patients, diagnosis was based on familial genetic survey or fortuitous abnormal results of blood samples. An initial serum level of ferritin greater than 1000 μg/L was a factor of severity for 50% of patient. These two elements must be taken into account to consider a population mass screening. Long time to diagnosis required a sensitization of the population to be aware of the clinical manifestations of hemochromatosis. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Allergic manifestations in patients with rheumatoid arthritis.

PubMed

Olsson, Asa Reckner; Wingren, Gun; Skogh, Thomas; Svernell, Olle; Ernerudh, Jan

2003-10-01

A functional dichotomy between Th1- and Th2-type immune responses has been suggested. This study was performed to investigate whether rheumatoid arthritis (RA), a disease with indications of Th1-deviated immune activation, is inversly related to atopic conditions which are Th2-mediated. Two hundred and sixty-three adult cases of RA, fulfilling the American Rheumatism Association (ARA) 1987 Revised Classification Criteria for RA, were identified in 1995 and compared with 541 randomly selected population referents. The presence of atopic manifestations was established through a postal questionnaire and by demonstrating circulating IgE antibodies to common allergens. RA was inversely associated with certain manifestations of rhinitis, which were regarded as the most reliable indicators of atopic disease in the present study. However, no negative association was seen between RA and asthma and eczema, respectively. The main results give some support for an inverse relationship between RA and rhinitis. The prevalence of circulating IgE antibodies was however similar in cases and controls, suggesting that the T-cell commitment mainly occurs in the affected organs.

The challenge of establishing treatment efficacy for cutaneous vascular manifestations of systemic sclerosis.

PubMed

Pauling, John D

2018-05-01

The cutaneous vascular manifestations of systemic sclerosis (SSc) comprise Raynaud's phenomenon, cutaneous ulceration, telangiectasia formation and critical digital ischaemia; each of which are associated with significant disease-related morbidity. Despite the availability of multiple classes of vasodilator therapy, many of which have been the subject of RCTs, a limited number of pharmacological interventions are currently approved for the management of cutaneous vascular manifestations of SSc. Areas covered: A major challenge has been demonstrating treatment efficacy with examples of promising therapies yielding contrasting results in controlled trial settings. Differences between consensus best-practice guidelines, evidence-based recommendations and marketing approvals in different jurisdictions has resulted in geographic variation in clinical practice concerning the management of cutaneous vascular manifestations of SSc. Difficulty demonstrating treatment efficacy risks waning industry engagement for drug development programmes in this field. This article highlights the key challenges in establishing treatment efficacy and barriers that must be overcome to support successful clinical trial programmes across the spectrum of cutaneous vascular manifestations of SSc. Expert commentary: The paucity of approved treatments for cutaneous vascular manifestations of SSc relates as much to challenges in clinical trial design and the need for reliable clinical trial endpoints, as to lack of therapeutic options.