546 research outputs found
Peixes marinhos costeiros da ilha de São Tomé (Golfo da Guiné).
Since the early works of Balthazar Osório, at the turn of the century, only few papers have been published on the ichthyofauna of São Tomé island. The papers dealing with these fishes were compilations of previous works or the results of a few scientific expeditions (e.g. "Galathea" and "Calypso"). In this paper, we present the results of several surveys carried out from the island over the last decade, together with an annotated revision of the known bibliography for the area. The result is an inventory of the coastal fish of São Tomé island. Our records (124 species belonging to 59 families) are based on fish captured,
photographed or observed whilst diving and also on those landed by local artisanal
fishermen. In this paper we report a total of 185 confirmed coastal species and 67 families. Twenty-seven of these are reported for the first time for the area, and three other unidentified species may represent new species to science. The best represented families are Carangidae (14 species), Serranidae (11 species), Gobiidae and Scombridae (8 species each). Despite its proximity to the African Continent, it is clear that these islands harbour a particular fish fauna, including several amphiatlantic species, which, in the eastern Atlantic, occur only around oceanic islands (e.g., Epinephelus ascencionis, Paranthias furcifer, Mulloidychtis martinicus, Bodianus pulchellus, Chromis multilineata, Gnatholepis
thomsoni, Melychthis niger). The coastal ichthyodiversity of São Tomé is apparently poorer than that of the adjacent coasts, showing a significant influence of the islands further west, St. Helena and Ascencion
A generator-produced gallium-68 radiopharmaceutical for PET imaging of myocardial perfusion
Lipophilic cationic technetium-99m-complexes are widely used for myocardial perfusion imaging (MPI). However, inherent uncertainties in the supply chain of molybdenum-99, the parent isotope required for manufacturing 99Mo/99mTc generators, intensifies the need for discovery of novel MPI agents incorporating alternative radionuclides. Recently, germanium/gallium (Ge/Ga) generators capable of producing high quality 68Ga, an isotope with excellent emission characteristics for clinical PET imaging, have emerged. Herein, we report a novel 68Ga-complex identified through mechanism-based cell screening that holds promise as a generator-produced radiopharmaceutical for PET MPI
Novel gallium(III) complexes transported by MDR1 P-glycoprotein: potential PET imaging agents for probing P-glycoprotein-mediated transport activity in vivo
AbstractBackground: Multidrug resistance (MDR) mediated by expression of MDR1 P-glycoprotein (Pgp) represents one of the best characterized barriers to chemotherapy in cancer patients. Positron emission tomography (PET) agents for analysis of Pgp-mediated drug transport activity in vivo would enable noninvasive assessment of chemotherapeutic regimens and MDR gene therapy.Results: Candidate Schiff-base phenolic gallium(III) complexes were synthesized from their heptadentate precursors and gallium(III)acetylacetonate. Crystal structures demonstrated a hexacoordinated central gallium with overall trans-pseudo-octahedral geometry. Radiolabeled 67Ga-complexes were obtained in high purity and screened in drug-sensitive (Pgp−) and MDR (Pgp+) tumor cells. Compared with control, lead compound 6 demonstrated antagonist-reversible 55-fold lower accumulation in Pgp-expressing MDR cells. Furthermore, compared with wild-type control, quantitative pharmacokinetic analysis showed markedly increased penetration and retention of 6 in brain and liver tissues of mdr1a/b(−/−) gene disrupted mice, correctly mapping Pgp-mediated transport activity at the capillary blood–brain barrier and hepatocellular biliary cannalicular surface in vivo.Conclusions: These results indicate that gallium(III) complex 6 is recognized by MDR1 Pgp as an avid transport substrate, thereby providing a useful scaffold to generate 68Ga radiopharmaceuticals for molecular imaging of Pgp transport activity in tumors and tissues in vivo using PET
Combined VEGF and CXCR4 antagonism targets the GBM stem cell population and synergistically improves survival in an intracranial mouse model of glioblastoma
Glioblastoma recurrence involves the persistence of a subpopulation of cells with enhanced tumor-initiating capacity (TIC) that reside within the perivascular space, or niche (PVN). Anti-angiogenic therapies may prevent the formation of new PVN but have not prevented recurrence in clinical trials, suggesting they cannot abrogate TIC activity. We hypothesized that combining anti-angiogenic therapy with blockade of PVN function would have superior anti-tumor activity. We tested this hypothesis in an established intracranial xenograft model of GBM using a monoclonal antibody specific for murine and human VEGF (mcr84) and a Protein Epitope Mimetic (PEM) CXCR4 antagonist, POL5551. When doses of POL5551 were increased to overcome an mcr84-induced improvement in vascular barrier function, combinatorial therapy significantly inhibited intracranial tumor growth and improved survival. Anti-tumor activity was associated with significant changes in tumor cell proliferation and apoptosis, and a reduction in the numbers of perivascular cells expressing the TIC marker nestin. A direct effect on TICs was demonstrated for POL5551, but not mcr84, in three primary patient-derived GBM isolates. These findings indicate that targeting the structure and function of the PVN has superior anti-tumor effect and provide a strong rationale for clinical evaluation of POL5551 and Avastin in patients with GBM
Effect of fulvic acids on lead-induced oxidative stress to metal sensitive Vicia faba L. plant
Lead (Pb) is a ubiquitous environmental pollutant capable to induce various morphological, physiological, and biochemical functions in plants. Only few publications focus on the influence of Pb speciation both on its phytoavailability and phytotoxicity. Therefore, Pb toxicity (in terms of lipid peroxidation, hydrogen peroxide induction, and photosynthetic pigments contents) was studied in Vicia faba plants in relation with Pb uptake and speciation. V. faba seedlings were exposed to Pb supplied as Pb(NO3)2 or complexed by two fulvic acids (FAs), i.e. Suwannee River fulvic acid (SRFA) and Elliott Soil fulvic acid (ESFA), for 1, 12, and 24 h under controlled hydroponic conditions. For both FAs, Pb uptake and translocation by Vicia faba increased at low level (5 mg l−1), whereas decreased at high level of application (25 mg l−1). Despite the increased Pb uptake with FAs at low concentrations, there was no influence on the Pb toxicity to the plants. However, at high concentrations, FAs reduced Pb toxicity by reducing its uptake. These results highlighted the role of the dilution factor for FAs reactivity in relation with structure; SRFA was more effective than ESFA in reducing Pb uptake and alleviating Pb toxicity to V. faba due to comparatively strong binding affinity for the heavy metal
Anticancer Gene Transfer for Cancer Gene Therapy
Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field
Contributions Made by CDC25 Phosphatases to Proliferation of Intestinal Epithelial Stem and Progenitor Cells
The CDC25 protein phosphatases drive cell cycle advancement by activating cyclin-dependent protein kinases (CDKs). Humans and mice encode three family members denoted CDC25A, -B and -C and genes encoding these family members can be disrupted individually with minimal phenotypic consequences in adult mice. However, adult mice globally deleted for all three phosphatases die within one week after Cdc25 disruption. A severe loss of absorptive villi due to a failure of crypt epithelial cells to proliferate was observed in the small intestines of these mice. Because the Cdc25s were globally deleted, the small intestinal phenotype and loss of animal viability could not be solely attributed to an intrinsic defect in the inability of small intestinal stem and progenitor cells to divide. Here, we report the consequences of deleting different combinations of Cdc25s specifically in intestinal epithelial cells. The phenotypes arising in these mice were then compared with those arising in mice globally deleted for the Cdc25s and in mice treated with irinotecan, a chemotherapeutic agent commonly used to treat colorectal cancer. We report that the phenotypes arising in mice globally deleted for the Cdc25s are due to the failure of small intestinal stem and progenitor cells to proliferate and that blocking cell division by inhibiting the cell cycle engine (through Cdc25 loss) versus by inducing DNA damage (via irinotecan) provokes a markedly different response of small intestinal epithelial cells. Finally, we demonstrate that CDC25A and CDC25B but not CDC25C compensate for each other to maintain the proliferative capacity of intestinal epithelial stem and progenitor cells
International experience with secundum atrial septal defect occlusion by the buttoned device
Several devices are available for transcatheter occlusion of atrial septal defect. This report describes the international experience with the buttoned device. During a 4.5-year period ending in February 1993, 180 transcatheter atrial septal defect occlusions were performed with the buttoned device. Patient age varied between 0.6 and 76 years and stretched atrial defect diameter between 5 and 25 mm. The defects were closed with 25 to 50 mm devices delivered through 8F (148 patients) or 9F (32 patients) sheaths. Twelve patients were adults whose defects were closed to prevent recurrence of cerebrovascular accidents caused by presumed paradoxic embolism. In the remaining patients the atrial defect was closed to treat the left-to-right shunt. The atrial septal defects were effectively occluded as demonstrated by (1) decrease in pulmonary-to-systemic flow ratio from 2.1 +/- 0.6 (mean +/- SD) to 1.05 +/- 0.1 (p 2 and disappearance of the diastolic murmur by auscultation; and (3) improvement in right ventricular volume overloading by echocardiogram. However, trivial to small shunts could be detected by color Doppler studies in 76 (45%) of 168 patients in whom such data are available. Complications included unbuttoning in 13 and whole-device embolization in 1. All patients remained stable, and retrieval of the device and surgical closure of the atrial septal defect were accomplished in 10 patients. Transcatheter retrieval was used in the remaining 4 patients. The incidence of unbuttoning, a major complication of the procedure, appeared to decrease with the increasing experience of the investigators and with device modification (third-generation). The follow-up duration varied between 1 month and 4 years. Six patients required surgery during the follow-up period. In the remaining patients (n = 160), clinical examination did not reveal signs of atrial shunts. Color Doppler studies revealed either complete disappearance of the previously demonstrated shunts or further diminution of their size. The results indicate that transcatheter occlusion of the atrial septal defects with buttoned devices is feasible, relatively safe, and effective, and it appears to be a viable alternative to surgery for some patients with secundum atrial septal defect. Complications are infrequent and should improve with experience.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31234/1/0000139.pd
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