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Tissue Accumulation (tissue + accumulation)
Selected AbstractsElevated organochlorines in the brain,hypothalamic,pituitary complex of intersexual shovelnose sturgeonENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2006Brian T. Koch Abstract Organochlorine compounds (OCs), including polychlorinated biphenyls and organochlorine pesticides, were used on lands adjacent to the Middle Mississippi River (MMR; USA) from 1930 through 1988, and they continue to occur in MMR fish. These compounds are estrogenic and/or antiandrogenic, and they alter hormone production and reception within the brain and gonads of male fish, resulting in intersexuality and/or suppressed gonadal development. To assess how OCs affect reproduction of MMR fish, we quantified OC accumulation, intersexuality, and gonadal development in male shovelnose sturgeon (Scaphirhynchus platorynchus) throughout the MMR during the spring of 2003. Gonads were observed for intersexual characteristics, weighed to calculate the gonadosomatic index (GSI), and examined histologically. Tissue accumulation of OCs was quantified in gonads, brain,hypothalamic,pituitary (BHP) complex, and fillets. Four of 48 mature males were identified macroscopically as intersexuals, and a fifth was found through histology (a 10.4% incidence). Intersexuals accumulated higher concentrations of OCs in the BHP complex compared with those of mature males. In addition, GSI and OC accumulation within the BHP complex, gonads, and fillets of mature males were negatively related. Exposure to OCs before or during sexual differentiation likely induces intersexuality in MMR shovelnose sturgeon, and exposure throughout gonadal maturation inhibits gonadal development. [source] D-2-Hydroxyglutaric acid inhibits creatine kinase activity from cardiac and skeletal muscle of young ratsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2003C. G. Da Silva Abstract Background, Tissue accumulation of high amounts of D-2-hydroxyglutaric acid (DGA) is the biochemical hallmark of the inherited neurometabolic disorder D-2-hydroxyglutaric aciduria (DHGA). Patients affected by this disease usually present hypotonia, muscular weakness, hypothrophy and cardiomyopathy, besides severe neurological findings. However, the underlying mechanisms of muscle injury in this disorder are virtually unknown. Materials and methods, In the present study we have evaluated the in vitro role of DGA, at concentrations ranging from 0·25 to 5·0 mm, on total, cytosolic and mitochondrial creatine kinase activities from skeletal and cardiac muscle of 30-day-old Wistar rats. We also tested the effects of various antioxidants on the effects elicited by DGA. Results, We first verified that total creatine kinase (CK) activity from homogenates was significantly inhibited by DGA (22,24% inhibition) in skeletal and cardiac muscle, and that this activity was approximately threefold higher in skeletal muscle than in cardiac muscle. We also observed that CK activities from mitochondrial (Mi-CK) and cytosolic (Cy-CK) preparations from skeletal muscle and cardiac muscle were also inhibited (12,35% inhibition) by DGA at concentrations as low as 0·25 mm, with the effect being more pronounced in cardiac muscle preparations. Finally, we verified that the DGA-inhibitory effect was fully prevented by preincubation of the homogenates with reduced glutathione and cysteine, suggesting that this effect is possibly mediated by modification of essential thiol groups of the enzyme. Furthermore, ,-tocopherol, melatonin and the inhibitor of nitric oxide synthase L-NAME were unable to prevent this effect, indicating that the most common reactive oxygen and nitrogen species were not involved in the inhibition of CK provoked by DGA. Conclusion, Considering the importance of creatine kinase activity for cellular energy homeostasis, our results suggest that inhibition of this enzyme by increased levels of DGA might be an important mechanism involved in the myopathy and cardiomyopathy of patients affected by DHGA. [source] Purification of Matrix Gla Protein From a Marine Teleost Fish, Argyrosomus regius: Calcified Cartilage and Not Bone as the Primary Site of MGP Accumulation in Fish,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2003DC Simes Abstract Matrix Gla protein (MGP) belongs to the family of vitamin K-dependent, Gla-containing proteins, and in mammals, birds, and Xenopus, its mRNA was previously detected in extracts of bone, cartilage, and soft tissues (mainly heart and kidney), whereas the protein was found to accumulate mainly in bone. However, at that time, it was not evaluated if this accumulation originated from protein synthesized in cartilage or in bone cells because both coexist in skeletal structures of higher vertebrates and Xenopus. Later reports showed that MGP also accumulated in costal calcified cartilage as well as at sites of heart valves and arterial calcification. Interestingly, MGP was also found to accumulate in vertebra of shark, a cartilaginous fish. However, to date, no information is available on sites of MGP expression or accumulation in teleost fishes, the ancestors of terrestrial vertebrates, who have in their skeleton mineralized structures with both bone and calcified cartilage. To analyze MGP structure and function in bony fish, MGP was acid-extracted from the mineralized matrix of either bone tissue (vertebra) or calcified cartilage (branchial arches) from the bony fish, Argyrosomus regius,, separated from the mineral phase by dialysis, and purified by Sephacryl S-100 chromatography. No MGP was recovered from bone tissue, whereas a protein peak corresponding to the MGP position in this type of gel filtration was obtained from an extract of branchial arches, rich in calcified cartilage. MGP was identified by N-terminal amino acid sequence analysis, and the resulting protein sequence was used to design specific oligonucleotides suitable to amplify the corresponding DNA by a mixture of reverse transcription-polymerase chain reaction (RT-PCR) and 5,rapid amplification of cDNA (RACE)-PCR. In parallel, ArBGP (bone Gla protein, osteocalcin) was also identified in the same fish, and its complementary DNA cloned by an identical procedure. Tissue distribution/accumulation was analyzed by Northern blot, in situ hybridization, and immunohistochemistry. In mineralized tissues, the MGP gene was predominantly expressed in cartilage from branchial arches, with no expression detected in the different types of bone analyzed, whereas BGP mRNA was located in bone tissue as expected. Accordingly, the MGP protein was found to accumulate, by immunohistochemical analysis, mainly in the extracellular matrix of calcified cartilage. In soft tissues, MGP mRNA was mainly expressed in heart but in situ hybridization, indicated that cells expressing the MGP gene were located in the bulbus arteriosus and aortic wall, rich in smooth muscle and endothelial cells, whereas no expression was detected in the striated muscle myocardial fibers of the ventricle. These results show that in marine teleost fish, as in mammals, the MGP gene is expressed in cartilage, heart, and kidney tissues, but in contrast with results obtained in Xenopus and higher vertebrates, the protein does not accumulate in vertebra of non-osteocytic teleost fish, but only in calcified cartilage. In addition, our results also indicate that the presence of MGP mRNA in heart tissue is due, at least in fish, to the expression of the MGP gene in only two specific cell types, smooth muscle and endothelial cells, whereas no expression was found in the striated muscle fibers of the ventricle. In light of these results and recent information on expression of MGP gene in these same cell types in mammalian aorta, it is likely that the levels of MGP mRNA previously detected in Xenopus, birds, and mammalian heart tissue may be restricted toregions rich in smooth muscle and endothelial cells. Our results also emphasize the need to re-evaluate which cell types are involved in MGP gene expression in other soft tissues and bring further evidence that fish are a valuable model system to study MGP gene expression and regulation. [source] Elemental signals regulating eosinophil accumulation in the lungIMMUNOLOGICAL REVIEWS, Issue 1 2001Paul S. Foster Summary: In this review we identify the elemental signals that regulate eosinophil accumulation in the allergic lung. We show that there are two interwoven mechanisms for the accumulation of eosinophils in pulmonary tissues and that these mechanisms are linked to the development of airways hyperreactivity (AHR). Interleukin-(IL)-5 plays a critical role in the expansion of eosinophil pools in both the bone marrow and blood in response to allergen provocation of the airways. Secondly, IL-4 and IL-13 operate within the allergic lung to control the transmigration of eosinophils across the vascular bed into pulmonary tissues. This process exclusively promotes tissue accumulation of eosinophils. IL-13 and IL-4 probably act by activating eosinophil-specific adhesion pathways and by regulating the production of IL-5 and eotaxin in the lung compartment. IL-5 and eotaxin co-operate locally in pulmonary tissues to selectively and synergistically promote eosinophilia. Thus, IL-5 acts systemically to induce eosinophilia and within tissues to promote local chemotactic signals. Regulation of IL-5 and eotaxin levels within the lung by IL-4 and IL-13 allows Th2 cells to elegantly co-ordinate tissue and peripheral eosinophilia. Whilst the inhibition of either the IL-4/IL-13 or IL-5/ eotaxin pathways resulted in the abolition of tissue eosinophils and AHR, only depletion of IL-5 and eotaxin concurrently results in marked attenuation of pulmonary inflammation. These data highlight the importance of targeting both IL-5 and CCR3 signalling systems for the resolution of inflammation and AHR associated with asthma. S.M. is a Postdoctoral Fellow funded by a grant from the Human Frontiers Foundation to P.S.F. and M.E.R. J.M. is supported by the German Research Association (grant MA 2241/1-1) and S.P.H by a NH&MRC CJ Martin Postdoctoral Fellowship. [source] Diet-induced central obesity and insulin resistance in rabbitsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1 2008S. Zhao Summary The present study was designed to examine whether rabbits fed a diet containing high fat and sucrose could develop obesity and insulin resistance (IR), the major pathophysiological features of metabolic syndrome. Male Japanese white rabbits were fed either a normal chow diet (control) or high fat and sucrose diet (HFSD) for 36 weeks. Plasma levels of triglycerides (TG), total cholesterol (TC), glucose and insulin were measured. To evaluate glucose metabolism, we performed an intravenous glucose tolerance test. In addition, we compared adipose tissue accumulation in HFSD-fed rabbits with that in normal rabbits. HFSD constantly and significantly led to an increase in body weight of HFSD-fed rabbits, caused by significantly higher visceral adipose tissue accumulation. Although there were no differences in plasma TG, TC, glucose, insulin levels and blood pressure between the two groups, HFSD-fed rabbits showed impaired glucose clearance associated with higher levels of insulin secretion compared to control rabbits. Our results showed that HFSD induced IR and increased adipose accumulation in rabbits, suggesting that HFSD-fed rabbits may become a model for research on human IR and obesity. [source] Vitamins E and C prevent the impairment of retention of an inhibitory avoidance task caused by arginine administrationJOURNAL OF NEUROCHEMISTRY, Issue 2002E. A. Reis Hyperargininemia is an inherited metabolic disease of urea cycle caused by the deficiency of arginase I activity, resulting in tissue accumulation of arginine (Arg). Patients affected by this disease usually develop spasticity, epilepsy and mental retardation as principal symptoms. Previous studies from our laboratory have showed that acute administration of Arg impairs retention of the inhibitory avoidance task and that l -NAME (NOS inhibitor) prevents this effect. In the present study, we investigated the effect of chronic treatment with antioxidants (vitamins E and C) on the retrieval of the inhibitory avoidance task in adults rats subjected to experimental model of acute hyperargininemia in order to investigate the participation of oxidative stress on this phenomenon. Sixty-day-old-rats were treated for one week with i.p. injection of saline (0.9%) or vitamins E and C (vit E 40 mg/kg and vit C 100 mg/kg). Twelve hours after the last injection Arg (0.8 g/kg) or an equivalent volume of saline were administered 1 h before training, 1 h before testing or immediately after training sessions. Memory was significantly impaired in Arg-treated group, whereas the rats chronically treated with vitamins E and C had this effect prevented. Present data strongly indicate that Arg administration impairs memory, an effect probably mediated by oxidative stress since treatment with vitamins E and C prevented amnesia. Assuming the possibility that this might occur in the human condition, reported results may be relevant to explain, at least in part, neurologic dysfunction associated with hyperargininemia. [source] EXPLORING PORPHYRA SPECIES FOR USE AS NITROGEN SCRUBBERS IN INTEGRATED AQUACULTUREJOURNAL OF PHYCOLOGY, Issue 2001Article first published online: 24 SEP 200 Carmona, R.1, Kraemer G. P.2, Zertuche, J. A.3, Chanes, L.4, Chopin, T.5, Neefus C.4,6 & Yarish, C.1 1Dept. of Ecol. and Evol. Biol., University of Connecticut, One University Place, Stamford, CT 06901, USA; 2Department of Environmental Sciences, State University of New York, Purchase, NY 10577 USA; 3IIO, Universidad Autonoma de Baja California. Ensenada,B.C., Mexico; 4DGETI-CBTis41, Mexico; 5CCSA, Dept. of Biol., University of New Brunswick, Saint John, N.B., E2L 4L5, Canada; 6Department of Plant Biology, University of New Hampshire, Durham, NH 03824, USA Finfish mariculture along the Northeast US coast continues to develop into a strong industry. At a regional level, mariculture can be a significant contributor to nutrient loading in coastal waters. Since macroalgae are able to concentrate nutrients and grow at high rates, they can be an useful tool for alleviating this problem. In addition, seaweed mariculture is by itself a multi-billion dollar industry, with the red alga Porphyra (nori) valued at over $US 1.8 billion. Local species and strains of Porphyra from the Northeast U.S.A. are being studied to determine their capacity as nutrient scrubbers under different nutrient and temperature conditions. P. purpurea was grown under two N sources (NO3- vs. NH4+). The fastest growth (up to 13% d-1) and greatest N content (ca. 7% DW) were measured in plants grown at 300 µM NH4+. Short-term NH4+ uptake by P. purpurea (strains from Maine and Long Island Sound) and by P. amplissima was not saturated at 150 µM, the highest concentration tested. The P. purpurea isolate from Maine took up NH4+ faster than did the Long Island Sound isolate. NH4+ uptake by P. amplissima was faster than uptake by either P. purpurea strain. The high growth rates obtained and the ability for N uptake and tissue accumulation make these species suitable for using as a biological nutrient removal system. [source] Modification of Gd-DTPA cystine copolymers with PEG-1000 optimizes pharmacokinetics and tissue retention for magnetic resonance angiographyMAGNETIC RESONANCE IN MEDICINE, Issue 1 2007Aaron M. Mohs Abstract The purpose of this study was to investigate the effect of PEGylation of novel biodegradable macromolecular polydisulfide Gd(III) complexes, gadolinium diethylenetriaminepentaacetate (GdDTPA) cystine copolymers (GDCP), on their pharmacokinetics and long-term Gd(III) tissue retention, and to demonstrate the potential application of PEGylated GDCP (PEG-GDCP) for MR angiography (MRA). The pharmacokinetics, biodistribution, and metabolic excretion of PEG1000 -GDCP (42.1,52.1 kDa; PEG: MW = 1000 Da) with three different PEG grafting degrees and GDCP (43.3 kDa) were investigated in Sprague-Dawley rats. Pharmacokinetic data were analyzed by means of an open two-compartment model. Initially all three PEG1000 -GDCP contrast agents (CAs) had a higher plasma concentration than GDCP, but after 30 min the Gd(III) concentration from the PEGylated agents rapidly decreased, resulting in significantly lower elimination half-life values. All of the biodegradable macromolecular CAs demonstrated low long-term Gd(III) tissue accumulation, while PEG1000 -GDCP had significantly lower accumulation in the liver than GDCP. In the rats, all CAs showed excellent vascular contrast enhancement in an MRA protocol with a long image acquisition time. Because PEG1000 -GDCP remained intravascular for an acceptable period for effective contrast-enhanced (CE)-MRA, and then excreted rapidly from the vasculature with minimal tissue retention, PEG1000 -GDCP shows a great promise as a blood-pool CA for MRA. Magn Reson Med 58:110,118, 2007. © 2007 Wiley-Liss, Inc. [source] Pediatric lung disease: From proteinases to pulmonary fibrosisPEDIATRIC PULMONOLOGY, Issue 5 2005Felix Chua MRCP Abstract One distinctive outcome of interstitial lung diseases in childhood is the abnormal accumulation of pulmonary extracellular matrix. The clinical consequence of such excessive connective tissue accumulation is known as pulmonary fibrosis. While numerous aspects of its pathogenesis have become familiar, many key events involved in its inception and progression still remain unclear. There is now compelling evidence that lung damage due to uncontrolled proteolysis may help drive critical processes that regulate fibrotic matrix remodeling. In this regard, a number of proteinases have been implicated in promoting both the initial lung injury and the fibroproliferative repair that follows. This review summarizes the knowledge of how different matrix-targeting enzymes may act to influence the development of pediatric pulmonary fibrosis. Understanding the scientific basis of this complex process may highlight opportunities to limit unwanted proteolysis and the intensity of its fibrotic sequelae. © 2005 Wiley-Liss, Inc. [source] Hyperaccumulation of selenium in hybrid striped bass: a functional food for aquaculture?AQUACULTURE NUTRITION, Issue 3 2008P.A. COTTER Abstract One method of increasing the value of aquacultured product is to produce fillets that are fortified with minerals that are beneficial to human health , that is enhance the functionality of an already healthy product. A good candidate mineral in this regard is selenium (Se) which is of vital importance to normal metabolism in humans. In order to evaluate the dose response and tissue accumulation of supplemental dietary Se, a study was undertaken with hybrid striped bass (HSB). Animals were fed diets supplemented with either organic (0,3.2 mg kg,1 as SelPlex®) or inorganic (0.2 and 0.4 mg kg,1 as sodium selenite) Se for 6 weeks. Because basal fishmeal-based diets contained 1.22 mg Se kg,1, doses of Se delivered equated to 1.22,4.42 mg kg,1. At trial end, greatest weight gain was observed in fish receiving 0.2 mg Se kg,1, irrespective of form (organic/inorganic). Se accumulation in HSB liver and fillet revealed a classical dose-response once a threshold level of 0.2 mg Se kg,1 was surpassed. Greatest tissue accumulation of Se was observed in fish fed the 3.2 mg Se kg,1 level (P > 0.0001). A 100 g portion of Se-enhanced HSB fillet would contain between 33 and 109 ,g Se, amounting to a dietary intake of between 25 and 80 ,g Se; a level that would satisfy present daily intake recommendations. Comparison of tissue Se levels indicated that the muscle provides a more conspicuous gauge of dietary Se dose-response than does liver. Dietary treatments of between 0.4 and 1.6 mg organic Se kg,1 reduced (P < 0.024) plasma glutathione peroxidase (GSH-Px) activity. No differences were observed in ceruloplasmin, lysozyme or GSH-Px activities between organic and inorganic Se when delivered at the 0.2 mg Se kg,1 level. Ceruloplasmin, lysozyme and GSH-Px levels were elevated (P , 0.025) in fish fed the diet containing 0.4 mg inorganic Se kg,1. [source] Characteristic rat tissue accumulation of nobiletin, a chemopreventive polymethoxyflavonoid, in comparison with luteolinBIOFACTORS, Issue 3-4 2002Akira Murakami Abstract Nobiletin (NOB), a polymethoxyflavonoid, is an effective anti-inflammatory and chemopreventive phytochemical found in citrus fruits. We compared the absorption and metabolism characteristics of NOB with those of luteolin (LT) in male SD rats. Each flavonoid (67.1 ,mol/kg of body weight) was given separately by gastric intubation, and then concentrations were measured at 1, 4, and 24 hours after administration. In the digestive organs, NOB showed a notable tendency for localizing into the mucous membrane and muscularis from 1 to 4 hours, in contrast to LT, though both NOB and LT were completely excreted within 24 hours. Further, significant amounts of NOB were detected in the whole liver and kidney specimens, whereas LT accumulation was slight. Although serum concentrations of NOB from 1 to 4 hours were comparable to those of LT, urinary concentrations of LT were significantly higher from 4 to 24 hours. Following glucuronidase/sulfatase treatments of urinary materials, we detected 3 types of mono-demethylated NOB, including 3,-demethyl-NOB, and two di-demethylated types, as well as 3,-demethyl-NOB alone in serum samples using liquid chromatography-mass spectral analysis. Our results suggest that the metabolic properties of polymethoxyflavonoids are distinct from those of other general flavonoids, because of their wide distribution and accumulation in tissue. [source] | |||||||||||||