Increased Expression of Angiotensin II Type 2 Receptors in the Solitary-Vagal Complex Blunts Renovascular Hypertension

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Oral health profile in patients infected with HTLV-1: Clinical findings, proviral load, and molecular analysis from HTLV-1 in saliva

Human T-lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and has also been implicated in several disorders, including periodontal disease. The proviral load is an important biological marker for understanding HTLV-1 pathogenesis and elucidating whether or not the virus is related to the clinical manifestation of the disease. This study describes the oral health profile of HTLV-1 carriers and HAM/TSP patients in order to investigate the association between the proviral load in saliva and the severity of the periodontal disease and to examine virus intra-host variations from peripheral blood mononuclear cells and saliva cells. It is a cross-sectional analytical study of 90 individuals carried out from November 2006 to May 2008. Of the patients, 60 were HTLV-1 positive and 30 were negative. Individuals from the HTLV-1 positive and negative groups had similar mean age and social-economic status. Data were analyzed using two available statistical software packages, STATA 8.0 and SPSS 11.0 to conduct frequency analysis. Differences of P?<?0.05 were considered statistically significant. HTLV-1 patients had poorer oral health status when compared to seronegative individuals. A weak positive correlation between blood and saliva proviral loads was observed. The mean values of proviral load in blood and saliva in patients with HAM/TSP was greater than those in HTLV-1 carriers. The HTLV-1 molecular analysis from PBMC and saliva specimens suggests that HTLV-1 in saliva is due to lymphocyte infiltration from peripheral blood. A direct relationship between the proviral load in saliva and oral manifestations was observed. J. Med. Virol. 84:1428-1436, 2012. (c) 2012 Wiley Periodicals, Inc.

Synthese und Evaluierung von (Radio)Liganden für den Free Fatty Acid Rezeptor 1

Der Free Fatty Acid Receptor 1 (FFAR1) ist ein G-Protein gekoppelter Rezeptor, welcher neben einer hohen Expression im Gehirn auch eine verstärkte Expressionsrate auf den β-Zellen des Pankreas aufweist. Diese Expressionsmuster machen ihn zu einem idealen Target für die Visualisierung der sogenannten β-Zell-Masse mittels molekularer bildgebender Verfahren wie der PET. Eine Entwicklung geeigneter Radiotracer für die β-Zell-Bildgebung würde sowohl für die Diagnostik als auch für die Therapie von Typ-1- und Typ-2-Diabetes ein wertvolles Hilfsmittel darstellen.rnAufbauend auf einem von Sasaki et al. publiziertem Agonisten mit einem vielversprechendem EC50-Wert von 5,7 nM wurden dieser Agonist und zwei weitere darauf basierende 19F-substituierte Moleküle als Referenzverbindungen synthetisiert (DZ 1-3). Für die 18F-Markierung der Moleküle DZ 2 und DZ 3 wurden die entsprechenden Markierungsvorläufer (MV 1-3) synthetisiert und anschließend die Reaktionsparameter hinsichtlich Temperatur, Lösungsmittel, Basensystem und Reaktionszeit für die nukleophile n.c.a. 18F-Fluorierung optimiert. Die abschließende Entschützung zum fertigen Radiotracer wurde mit NaOH-Lösung durchgeführt und die Tracer injektionsfertig in isotonischer NaCl-Lösung mit radiochemischen Ausbeuten von 26,9 % ([18F]DZ 2) und 39 % ([18F]DZ 3) erhalten.rnZusätzlich wurde ein Chelator zur 68Ga-Markierung an den Liganden gekoppelt (Verb. 46) und die Markierungsparameter optimiert. Nach erfolgter Markierung mit 95 % radiochemischer Ausbeute, wurde der Tracer abgetrennt und in vitro Stabilitätsstudien durchgeführt. Diese zeigten eine Stabilität von mehr als 90 % über 120 min in sowohl humanem Serum (37 °C) als auch isotonischer NaCl-Lösung.rnMit einem ebenfalls synthetisierten fluoreszenzmarkierten Derivat des Liganden (Verb. 43) wurden erste LSM-Bilder an sowohl Langerhansschen Inseln als auch FFAR1-tragenden RIN-M Zellen durchgeführt, welche einen vielversprechenden Uptake des neuen Liganden in die Zellen zeigen. Weitere Untersuchungen und biologische Evaluierungen stehen noch aus. Mit den Referenzsubstanzen wurden zusätzlich Vitalitätsstudien an Langerhansschen Inseln durchgeführt, um einen negativen toxischen Einfluss auszuschließen.rn

Evidence for a new fumarate hydratase gene mutation in a unilateral type 2 segmental leiomyomatosis

Multiple cutaneous and uterine leiomyomata syndrome (MCUL; MIM 150800) is a rare condition that sometimes predisposes to renal cancer. It is caused by deleterious mutations in the fumarate hydratase (FH) gene. In many patients, skin leiomyomas have been reported to develop according to a segmental type 1 or type 2 distribution. We report a patient showing multiple leiomyomas distributed according to a segmental type 2 distribution and covering several areas exclusively on the left side of his body.

Regulation and transcript analysis of the ceroperon responsible for quorum sensing in Rhodobacter sphaeroides 2.4.1

Rhodobacter sphaeroides 2.4.1 is a Gram negative facultative photoheterotrophic bacterium that has been shown to have an N-acyl homoserine lactone-based quorum sensing system called cer for c&barbelow;ommunity e&barbelow;scape r&barbelow;esponse. The cer ORFs are cerR, the transcriptional regulator, cerI, the autoinducer synthase and cerA , whose function is unknown. The autoinducer molecule, 7,8- cis-N-(tetradecenoyl) homoserine lactone, has been characterized. The objective of this study was to identify an environmental stimulus that influences the regulation of cerRAI and, to characterize transcription of the cer operon. ^ A cerR::lacZ transcriptional fusion was made and β-Galactosidase assays were performed in R. sphaeroides 2.4.1 strains, wild type, AP3 (CerI−) and AP4 (CerR−). The cerR::lacZ β-Galactosidase assays were used as an initial survey of the mode of regulation of the Cer system. A cerA::lacZ translational fusion was created and was used to show that cerA can be translated. The presence of 7,8-cis-N-(tetradecenoyl) homoserine lactone was detected from R. sphaeroides strains wild type and AP4 (CerR−) using a lasR::lacZ translational fusion autoinducer bioassay. The cerR::lacZ transcriptional fusion in R. sphaeroides 2.4.1 wild type was tested under different environmental stimuli, such as various carbon sources, oxygen tensions, light intensities and culture media to determine if they influence transcription of the cer ORFs. Although lacZ assay data implicated high light intensity at 100 W/m2 to stimulate cer transcription, quantitative Northern RNA data of the cerR transcript showed that low light intensity at 3 W/m2 is at least one environmental stimulus that induces cer transcription. This finding was supported by DNA microarray analysis. Northern analysis of the cerRAI transcript provided evidence that the cer ORFs are co-transcribed, and that the cer operon contains two additional genes. Bioinformatics was used to identify genes that may be regulated by the Cer system by identifying putative lux box homologue sequences in the presumed promoter region of these genes. Genes that were identified were fliQ, celB and calsymin, all implicated in interacting with plants. Primer extension was used to help localize cis-elements in the promoter region. The cerR::lacZ transcriptional fusion was monitored in a subset of different global DNA binding transcriptional regulator mutant strains of R. sphaeroides 2.4.1. Those regulators involved in maintaining an anaerobic photosynthetic lifestyle appeared to have an effect. Collectively, the data imply that R. sphaeroides 2.4.1 activates the Cer system when grown anaerobic photosynthetically at low light intensity, 3 W/m2, and it may be involved in an interaction with plants. ^