Paroxysmal Nocturnal Hemoglobinuria (Pnh) : Brain Mri Ischemic Lesions in Neurologically Asymtomatic Patients

This study investigated for the first time brain ischemic involvement in 19 consecutive neurologically asymptomatic PNH patients by non-enhanced cerebral MRI, and by intracranial arterial and venous angio-MRI. Eleven cases (58%, 7 aged 5 mm, and 5 cases a score >4 by the age-related white matter changes (ARWMC) scale. Compared with age and sex-matched controls (1:2 ratio), patients showed an increased frequency of periventricular WM vascular degeneration (32% versus 5.2%, p = 0.04) and of severe lesions (ARWMC scale score >4) (26% versus 2.6%, p = 0.05), and a higher overall ARWMC scale score (3.5 \uc2\ub1 1.07 versus 2.0 \uc2\ub1 0.8, mean \uc2\ub1 SD, p < 0.0001). Notably, vascular abnormalities suspected for prior partial venous thrombosis, were observed in PNH cases only. MRI lesions were not related to blood counts, hemolytic markers, clone size, disease duration, and therapy with eculizumab. Neurological examination was unremarkable in all patients but one (Parkinson disease). Psychiatric assessment revealed a case of generalized anxiety disorder, 1 bipolar disorder type 2, and 1 adjustment disorder. In conclusion, brain MRI may be useful at diagnosis and during the course of the disease to explore subclinical neurological involvement

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic Structure And Phenotypic Variation In Wild Populations Of The Medicinal Tetraploid Species Bromelia Antiacantha (bromeliaceae)

Premise of the study: The patterns of genetic structure in plant populations are mainly related to the species life history and breeding system, and knowledge of these patterns is necessary for the management, use, and conservation of biological diversity. Polyploidy is considered an important mode of evolution in plants, but few studies have evaluated genetic structure of polyploid populations. We studied the patterns of genetic structure and morphological variation of Bromelia antiacantha (Bromeliaceae) populations, a polyploid terrestrial species.Methods: Microsatellite markers and morphological analyses were used to explore patterns of genetic and morphological diversity in wild populations of B. antiacantha.Key results: The results of our simple-sequence repeat analyses supported that B. antiacantha is a polyploid species. The inbreeding coefficients were high and significant in all populations (F IS = 0.431), indicating homozygote excess. Bromelia antiacantha showed high levels of genetic differentiation among populations (F ST = 0.224) and therefore was highly structured. High morphological variation was observed in fruit phenotypic traits in the populations studied.Conclusions: The levels of genetic diversity and the pattern of the population ' s structure may be related to the low recruitment of seeds, clonal reproduction, and the population ' s colonization history. The genetic and morphological variability displayed in this study are important issues in planning the conservation and exploitation of this resource in a sustainable way. © 2011 Botanical Society of America.98915111519Barbará, T., Lexer, C., Martinelli, G., Mayo, S., Fay, M.F., Heuertz, M., Within-population spatial genetic structure in four naturally fragmented species of a neotropical inselberg radiation, Alcantarea imperialis, A. geniculata, A. glaziouana and A. regina (Bromeliaceae) (2008) Heredity, 101, pp. 285-296Barbará, T., Martinelli, G., Fay, M.F., Mayo, J., Lexer, C., Population differentiation and species cohesion in two closely related plants adapted to neotropical high-altitude 'inselbergs,'Alcantarea imperialis and Alcantarea geniculata (Bromeliaceae) (2007) Molecular Ecology, 16, pp. 1981-1992Barbará, T., Martinelli, G., Palma-Silva, C., Fay, M.F., Mayo, S., Lexer, C., Genetic relationships and variation in reproductive strategies in four closely related bromeliads adapted to neotropical 'inselbergs': Alcantarea glaziouana, A. regina, A. geniculata and A. imperialis (Bromeliaceae) (2009) Annals of Botany, 103, pp. 65-77Barbará, T., Palma-Silva, C., Paggi, G.M., Bered, F., Fay, M.F., Lexer, C., Cross-species transfer of nuclear microsatellites markers: Potential and limitations (2007) Molecular Ecology, 16, pp. 3759-3767Borba, E.L., Funch, R.R., Ribeiro, P.L., Smidt, E.C., Silva-Pereira, V., Demography, and genetic and morphological variability of the endangered Sophronitis sincorana (Orchidaceae) in the Chapada Diamantina, Brazil (2007) Plant Systematics and Evolution, 267, pp. 129-146Brown, G.K., Gilmartin, A.J., Chromosome numbers in Bromeliaceae (1989) American Journal of Botany, 76, pp. 657-665Canela, M.B.F., Sazima, M., The pollination of Bromelia antiacantha (Bromeliaceae) in southeastern Brazil: Ornithophilous versus melittophilous features (2005) Plant Biology, 7, pp. 411-416Carnaval, A.C., Moritz, C., Historical climate modelling predicts patterns of current biodiversity in the Brazilian Atlantic forest (2008) Journal of Biogeography, 35, pp. 1187-1201Cascante-Marín, A., Oostermeijer, J.G.B., Wolf, J.H.D., den Nijs, J.C.M., Reproductive biology of the epiphytic bromeliad Werauhia gladioliflora in a premontane tropical forest (2005) Plant Biology, 7, pp. 203-209Cavallari, M.M., Forzza, R.C., Veasey, E.A., Zucchi, M.I., Oliveira, G.C.X., Genetic variation in three endangered species of Encholirium (Bromeliaceae) from Cadeia do Epinhaço, Brazil, detected using RAPD markers (2006) Biodiversity and Conservation, 15, pp. 4357-4373Ceita, G.O., Assis, J.G.A., Guedes, M.L.S., Oliveira, A.N.P.C., Cytogenetics of Brazilian species of Bromeliaceae (2008) Botanical Journal of Linnean Society, 158, pp. 189-193Chapman, H.M., Parh, D., Oraguzie, N., Genetic structure and colonizing success of a clonal, weedy species, Pilosella officinarum (Asteraceae) (2000) Heredity, 84, pp. 401-409Crawford, D.J., Enzyme electrophoresis and plant systematics (1989) Isozymes in plant biology. Dioscorides Press, , In D. E. Soltis and P. S. Soltis [eds.], Portland, Oregon, USADoyle, J.J., Doyle, J.L., Isolation of plant DNA from fresh tissue (1990) Focus (San Francisco, Calif.), 12, pp. 13-15Duarte, A.S., da Silva, C.V., Puchalski, A., Mantovani, M., Silva, J.Z., Reis, M.S., Estrutura demográfica e produçã o de frutos de Bromelia antiacantha Bertol (2007) Revista Brasileira de Plantas Medicinais, 9, pp. 106-112Estoup, A., Jarne, P., Cornuet, J.M., Homoplasy and mutation model at microsatellite model and their consequences for population genetics analysis (2002) Molecular Ecology, 11, pp. 1591-1604Evanno, G., Regnaut, S., Goudet, J., Detecting the numbers of clusters of individuals using the software Structure: A simulation study (2005) Molecular Ecology, 14, pp. 2611-2620Gitaí, J.S.F., (2006) Contribuiçã o de Características Citogenéticas e MolecularesàSistemática de Bromeliaceae, , Ph.D. dissertation, Universidade Federal de Pernambuco, Recife, BrazilGitaí, J., Horres, R., Benko-Iseppon, A.M., Chromosomal features and evolutions of Bromeliaceae (2005) Plant Systematics and Evolution, 253, pp. 65-80Givnish, T.J., Barfus, M.H.J., van Ee, B., Riina, R., Schulte, K., Horres, R., Gonsiska, P.A., Phylogeny, adaptive radiation, and historical biogeography in Bromeliaceae: Insights from an eightlocus plastid phylogeny (2011) American Journal of Botany, 98, pp. 872-895Gliddon, C., Belhassen, E., Gouyon, P.H., Genetic neighborhoods in plants with diverse systems of mating and different patterns of growth (1987) Heredity, 59, pp. 29-32González-Astorga, J., Cruz-Angón, A., Flores-Palacios, A., Vovides, A.P., Diversity and genetic structure of the Mexican endemic epiphyte Tillandsia achyrostachys E. Morr. ex Baker var. achyrostachys (Bromeliaceae) (2004) Annals of Botany, 94, pp. 545-551Gower, J.C., A general coefficient of similarity and some of its properties (1971) Biometrics, 27, pp. 857-874Hartl, D.L., Clark, A.G., (1997) Principles of populations genetics, 3rd ed, , Sinauer, Sunderland, Massachusetts, USAHmeljevski, K.V., Reis, A., Montagna, T., Reis, M.S., Genetic diversity, genetic drift and mixed mating system in small subpopulations of Dyckia ibiramensis, a rare endemic bromeliad from Southern Brazil (2011) Conservation Genetics, 12, pp. 761-769Hokanson, K., Hancock, J., Levels of allozymic diversity in diploid and tetraploid Vaccinium sect. Cyanococcus (blueberries) (1998) Canadian Journal of Plant Science, 78, pp. 327-332Jorge, L.I.F., Ferro, V.O., Reconhecimento da espécie Bromelia antiacantha Bertol. Características botânicas e fitoquímicas (1993) Revista de Farmacia y Bioquímica, 29, pp. 69-72López-Pujol, J., Bosch, M., Simon, J., Blanche, C., Allozyme diversity in the tetraploid endemic Thymus loscosii (Lamiaceae) (2004) Annals of Botany, 93, pp. 323-332Lorscheitter, M.L., Contribution to the Holocene history of Atlantic rain forest in the Rio Grande do Sul State, southern Brazil (2003) Revista del Museo Argentino de Ciencia Naturales, 5, pp. 261-271Murawski, A.D., Hamrick, J.L., Local genetic and clonal structure in the tropical terrestrial bromeliad, Aechmea magdalenae (1990) American Journal of Botany, 77, pp. 1201-1208Nei, M., Analysis of gene diversity in subdivided populations (1973) Proceedings of the National Academy of Sciences, USA, 70, pp. 3321-3323Nei, M., F-statistics and analysis of gene diversity in subdivided populations (1977) Annals of Human Genetics, 41, pp. 225-233Norero, N., Malleville, J., Huarte, M., Feingold, S., Cost efficient potato (Solanum tuberosum L.) cultivar identification by microsatellite amplification (2002) Potato Research, 45, pp. 131-138Nybom, H., Comparison on different nuclear DNA markers for estimating intraspecific genetic diversity in plants (2004) Molecular Ecology, 13, pp. 1143-1155Ota, T., (1993) DISPAN: Genetic distance and phylogenetic analysis, , http://homes.bio.psu.edu/people/Faculty/Nei/, Computer program and documentation distributed by the author, website: [accessed 10 December 2009]Otto, S.P., Whitton, J., Polyploid incidence and evolution (2000) Annual Review of Genetics, 34, pp. 401-437Paggi, G.M., Palma-Silva, C., Cidade, F.W., Sousa, A.C.B., Souza, A.P., Wendt, T., Lexer, C., Bered, F., Isolation and characterization of microsatellite loci in Pitcairnia albiflos (Bromeliaceae), an endemic bromeliad from Atlantic Rainforest, and cross-amplification in other species (2008) Molecular Ecology Research, 8, pp. 980-982Palma-Silva, C., Cavallari, M.M., Barbará, T., Lexer, C., Gimenes, A., Bered, F., Bodanese-Zanettini, M.H., A set of polymorphic microsatellite loci for Vreisea gigantea and Alcantarea imperialis (Bromeliaceae) and cross-amplification in other bromeliads species (2007) Molecular Ecology Notes, 7, pp. 654-657Palma-Silva, C., Lexer, C., Paggi, G.M., Barbará, T., Bered, F., Bodanese-Zanettini, M.H., Range-wide patterns of nuclear and chloroplast DNA diversity in Vriesea gigantea (Bromeliaceae), a neotropical forest species (2009) Heredity, 103, pp. 503-512Palma-Silva, C., Santos, D.G., Kaltchuk-Santos, E., Bodanese-Zanettini, M.H., Chromosome numbers, meiotic behavior, and pollen viability of species Vriesea and Aechmea genera (Bromeliaceae) native to Rio Grande do Sul, Brazil (2004) American Journal of Botany, 91, pp. 804-807Pillar, V.D., (2008) Multiv, software for multivariate exploratory analysis, randomization testing and bootstrap resampling (for Macintosh and Windows OS), , http://ecoqua.ecologia.ufrgs.br, Computer program and documentation distributed by the author, website: [accessed 5 December 2009]Pritchard, J.K., Stephens, M., Donnelly, P., Inference of population structure using multilocus genotype data (2000) Genetics, 155, pp. 945-959Prober, S.M., Spindler, L.H., Brown, A.H.D., Conservation of the grassy white box woodlands: Effects of remnant population size on genetic diversity in the allotetraploid herb Microseris lanceolata (1998) Conservation Biology, 12, pp. 1279-1290Ramsey, J., Schemske, D.W., Pathways, mechanisms, and rates of polyploid formation in flowering plants (1998) Annual Review of Ecology and Systematics, 29, pp. 467-501Rohlf, F.J., (2000) NTSYS-pc numerical taxonomy and multivariate analysis system, version 2.11a, , Exeter Software, Setauket, New York, USASantos, D.S., Puchalski, A., Gomes, G.S., Mantovani, M., Silva, J.Z., Reis, M.S., Variaçã o no período de germinaçã o de sementes em uma populaçã o natural de Bromelia antiacantha Bertol (2004) Revista Brasileira de Plantas Medicinais, 6, pp. 35-41Sarthou, C., Samadi, S., Boisseler-Dubayle, M.C., Genetic structure of the saxicole Pitcairnia geyskesii (Bromeliaceae) on inselbergs in French Guiana (2001) American Journal of Botany, 88, pp. 861-868Sgorbati, S., Labra, M., Gruni, E., Barcaccia, G., Galasso, G., Boni, U., Mucciarelli, M., A survey of genetic diversity and reproductive biology of Puya raimondii (Bromeliaceae), the endangered queen of the Andes (2004) Plant Biology, 6, pp. 222-230Smith, L.B., Downs, R.J., (1979) Bromelioideae (Bromeliaceae), 3. , Flora Neotropica. Monograph 14, Hafner Press, New York, New York, USASoltis, D.E., Gilmartin, J., Rieseberg, L., Gardner, S., Genetic variation in the epiphytes Tillandsia ionantha and T. recurvata (Bromeliaceae) (1987) American Journal of Botany, 74, pp. 531-537Soltis, P.S., Soltis, D.E., The role of genetic and genomic attributes in the success of polyploids. National Academy of Sciences colloquium: Variation and evolution in plants and microorganisms: Toward a new synthesis 50 years after Stebbins (2000) Proceedings of the National Academy of Sciences, 97, pp. 7051-7705. , June 20, 2000, Irvine, California, USA., USAStebbins, G.L., Polyploidy in plants: Unresolved problems and prospects (1980) Polyploidy, pp. 495-520. , In W. H. Lewis [ed.], Plenum Press, New York, New York, USAStebbins Jr., G.L., Types of polyploids: Their classification and significance (1947) Advances in Genetics, 1, pp. 403-429Stiles, F.G., Geographical aspects of bird flower coevolution with particular reference to Central America (1981) Annals of the Missouri Botanical Garden, 68, pp. 323-351Thomé, M.T., Zamudio, K.R., Giovanelli, J.G.R., Haddad, C.F.B., Baldissera, F.A., Alexandrino, J., Phylogeography of endemic toads and post-Pliocene persistence of the Brazilian Atlantic Forest (2010) Molecular Phylogenetics and Evolution, 55, pp. 1018-1031Thrall, P.H., Young, A., AUTOTET: A program for analysis of autotetraploid genotypic data (2000) Journal of Heredity, 91, pp. 348-34

Characterization Of The Inclusion Complex Ropivacaine: β-cyclodextrin [caracterização Do Complexo De Inclusão Ropivacaína: β-ciclodextrina]

Ropivacaine (RVC) is a widely used local anesthetic. The complexation of RVC with β-cyclodextrin (β-CD) is of great interest for the development of more efficient local anesthetic formulations. The present work focuses on the characterization of the RVC:β-CD complex by nuclear magnetic resonance (NMR). The stoichiometry of the complex is 1:2 RVC:β-CD. DOSY-NMR shows that the association constant is 55.5 M-1. Longitudinal relaxation time results show that RVC changes its mobility in the presence of β-CD. This study is focused on the physicochemical characterization of inclusion complexes that are potentials options for pain treatment.30512031207Covino, B.G., Vassalo, H.G., (1985) Anestésicos locais: Mecanismos de ação e uso clínico, , Colina: Rio de JaneiroCourtney, K.R., Strichartz, G.R., (1987) Local Anesthetics, Handbook of Experimental Pharmacology, , Springer-Verlag: BerlinGupta, S.P., (1991) Chem. Rev, 91, p. 1109Kuzma, P.J., Kline, M.D., Calkins, M.D., Staats, P.S., (1997) Reg. Anesth, 22, p. 543McClure, J.H., (1996) Brit. J. Anaesth, 76, p. 300Cederholm, I., (1997) Drug Saf, 16, p. 391Knudsen, K., Suurkula, M.B., Blomberg, S., Sjovall, J., Edvardsson, N., (1997) Br. J. Anesth, 78, p. 507Emanuelsson, B.M., Person, J., Sadin, S., Alm, C., Gustafsson, L.L., (1997) Ther. Drug Monit, 19, p. 126O'Keeffe, N.J., Healy, T.E.J., (1999) Pharmacol. Ther, 84, p. 233Bennett, G., Deer, T., Stuart, D.P., Rauck, R., Yaksh, T., Hassenbusch, S.J., (2000) J. Pain Symp. Manag, 20, p. 44Whiteside, J.B., Wildsmith, J.A.W., (2001) Br. J. Anesth, 87, p. 27de Araújo, D.R., Pinto, L.M.A., Braga, A.F.A., de Paula, E., (2003) Rev. Bras. Anestesiol, 53, p. 663de Araújo, D.R., Fraceto, L.F., Braga, A.F.A., de Paula, E., (2005) Rev. Bras. Anestesiol, 55, p. 316Loftsson, T., Masson, M., (2001) Int. J. Pharm, 225, p. 15McCormack, B., Gregoriadis, G., (1998) Int. J. Pharm, 162, p. 59Matioli, G.Ciclodextrinas e suas aplicações em: alimentos, fármacos, cosméticos, agricultura, biotecnologia, química analítica e produtos gerais, Ed. Eduem: Maringá, 2000Irie, T., Uekama, K., (1997) J. Pharm. Sci, 86, p. 147Pinto, L.M.A., de Jesus, M.B., de Paula, E., Lino, A.C.S., Alderetec, J.B., Duarte, H.A., Takahata, Y., (2004) J. Mol. Struct. (Theochem), 678, p. 63Pinto, L.M.A., Fraceto, L.F., Santana, M.H., Pertinhez, T.A., Oyama-Junior, S., de Paula, E., (2005) J. Pharm. Biomed. Anal, 39, p. 956Kopecký, F., Vojteková, M., Kaclik, P., Demko, M., Bieliková, Z., (2004) J. Pharm. Pharmacol, 56, p. 581Etos, S., Noda, H., Noda, A., (1994) J. Chromatogr., B: Anal. Technol. Biomed. Life Sci, 19, p. 385Loukas, Y.L., Vraka, V., Gregoriadis, G., (1998) Int. J. Pharm, 162, p. 137Ivanov, P.M., Salvatierra, D., Jaime, C., (1996) J. Org. Chem, 61, p. 7012Laverde Jr., A., da Conceição, G.J.A., Queiroz, S.C.N., Fujiwara, F.Y., Marsaioli, A.J., (2002) Magn. Reson. Chem, 40, p. 433Johnson Jr., C.S., (1999) Prog. Nucl. Magn. Reson. Spectrosc, 34, p. 203Xiliang, G., Yu, Y., Guoyan, Z., Guomei, Z., Jianbin, C., Shaomin, S., (2003) Spectrochim. Acta, Part A, 59, p. 3379Bratu, I., Gavira-Vallejo, J.M., Hernanz, A., (2005) Biopolymers, 77, p. 361Ikeda, Y., Hirayama, F., Arima, H., Uekama, K., Yoshitake, Y., Harano, K., (2004) J. Pharm. Sci, 93, p. 1659Zouvelekis, D., Yannakopoulou, K., Mavridis, I.M., Antoniadou-Vyza, A., (2002) Carbohydr. Res, 337, p. 1387Munoz-Botella, S., Martin, M.A., Del Castillo, B., Menendez, J.C., Vazquez, L., Lerner, D.A., (1996) J. Pharm. Biomed. Anal, 14, p. 909Garcia-Rio, L., Hervés, P., Leis, J.R., Mejuto, J.C., Pérez-Juste, J., Rodriguez-Dafonte, P., (2006) Org. Biomol. Chem, 4, p. 1038Abou-Zeid, O.K., (2005) Spectrochim. Acta, Part A, 62, p. 245Pascal, B., Maud, G., Georges, D., Adelin, A., Valery, B., Bruno, P., Didier, C., Brigitte, E., (2005) J. Pharm. Pharmaceut. Sci, 8, p. 164Morris, K.F., Johnson Jr., C.S., (1992) J. Am. Chem. Soc, 114, p. 3139Morris, K.F., Johnson Jr., C.S., (1993) J. Am. Chem. Soc, 115, p. 4291Dollo, G., Le Corre, P., Chevanne, F., Le Verge, R., (1996) Int. J. Pharm, 136, p. 165Fraceto, L.F., Spisni, A., Schreier, S., de Paula, E., (2005) Biophys. Chem, 115, p. 11Fraceto, L.F., Pinto, L.M.A., Franzoni, L., Braga, A.A.C., Spisni, A., Schreier, S., de Paula, E., (2002) Biophys. Chem, 99, p. 22