1,246 research outputs found
High correlation between Chagas' disease serology and PCR-based detection of Trypanosoma cruzi kinetoplast DNA in bolivian children living in an endemic area
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Previous issue date: 1994Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de BioquÃmica e Biologia Molecular. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.UMR CNRS/ ORSTOM, Génétique Moléculaire des Parasites et des Vecteurs. CP 9214, La Paz, Bolivia.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de BioquÃmica e Biologia Molecular. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Universidad Mayor de San Andres. Instituto Boliviano de Biologia de Altura. La Paz, Bolivia.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de BioquÃmica e Biologia Molecular. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de BioquÃmica e Biologia Molecular. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.UMR CNRS/ ORSTOM, Génétique Moléculaire des Parasites et des Vecteurs. CP 9214, La Paz, Bolivia.The detection of Tr)tpunosomu crirzi kinetoplast DNA by polymerase chain reaction (PCR) amplification is a potentially
powerful tool for the parasitological diagnosis of Chagas’ disease. We have applied this technique in a field situation in Bolivia,
where 45 children from a primary school were subjected to serological testing, buffy coat analysis and PCR diagnosis. 26 of the 28
serology-positive individuals were also positive by PCR. In addition, two serology-negative children gave a positive result by PCR,
including one who was positive in the buffy coat test. These results suggest that PCR detection of T. cruzi DNA in blood can be a
very useful complement to serology in Chagas’ disease diagnosis in Bolivia
Numerical Study of Competing Spin-Glass and Ferromagnetic Order
Two and three dimensional random Ising models with a Gaussian distribution of
couplings with variance and non-vanishing mean value are studied
using the zero-temperature domain-wall renormalization group (DWRG). The DWRG
trajectories in the () plane after rescaling can be collapsed on two
curves: one for and other for . In the first case
the DWRG flows are toward the ferromagnetic fixed point both in two and three
dimensions while in the second case flows are towards a paramagnetic fixed
point and spin-glass fixed point in two and three dimensions respectively. No
evidence for an extra phase is found.Comment: a bit more data is taken, 5 pages, 4 eps figures included, to appear
in PR
Instantons and Matter in N=1/2 Supersymmetric Gauge Theory
We extend the instanton calculus for N=1/2 U(2) supersymmetric gauge theory
by including one massless flavor. We write the equations of motion at leading
order in the coupling constant and we solve them exactly in the
non(anti)commutativity parameter C. The profile of the matter superfield is
deformed through linear and quadratic corrections in C. Higher order
corrections are absent because of the fermionic nature of the back-reaction.
The instanton effective action, in addition to the usual 't Hooft term,
includes a contribution of order C^2 and is N=1/2 invariant. We argue that the
N=1 result for the gluino condensate is not modified by the presence of the new
term in the effective action.Comment: 33 pages, harvmac; v2: minor changes, added references; v3: added
analysis of the instanton measure in section
In vitro and in vivo analyses of eFAP:a novel FAP-targeting small molecule for radionuclide theranostics and other oncological interventions
Background: Fibroblast activation protein (FAP), a transmembrane serine protease overexpressed by cancer-associated fibroblasts in the tumor stroma, is an interesting biomarker for targeted radionuclide theranostics. FAP-targeting radiotracers have demonstrated to be superior to [18F]FDG PET/CT in various solid cancers. However, these radiotracers have suboptimal tumor retention for targeted radionuclide therapy (TRT). We aimed to develop a novel FAP-targeting pharmacophore with improved pharmacokinetics by introducing a substitution at the 8-position of (4-quinolinoyl)-glycyl-2-cyanopyrrolidine, which allows for conjugation of a chelator, dye, or other payloads. Results: Here we showed the synthesis of DOTA-conjugated eFAP-6 and sulfo-Cyanine5-conjugated eFAP-7. After chemical characterization, the uptake and specificity of both tracers were determined on FAP-expressing cells. In vitro, [111In]In-eFAP-6 demonstrated a superior affinity and a more rapid, although slightly lower, peak uptake than gold standard [111In]In-FAPI-46. Confocal microscopy demonstrated a quick FAP-mediated internalization of eFAP-7. Studies with HT1080-huFAP xenografted mice confirmed a more rapid uptake of [177Lu]Lu-eFAP-6 vs. [177Lu]Lu-FAPI-46. However, tumor retention at 24 h post injection of [177Lu]Lu-eFAP-6 was lower than that of [177Lu]Lu-FAPI-46, hereby currently limiting its use for TRT. Conclusion: The superior affinity and faster tumor accumulation of eFAP-6 over FAPI-46 makes it a suitable compound for radionuclide imaging. After further optimization, the eFAP series has great potential for various oncological interventions, including fluorescent-guided surgery and effective targeted radionuclide theranostics.</p
Applying HDACis to increase SSTR2 expression and radiolabeled DOTA-TATE uptake:from cells to mice
Aims: The aim of our study was to determine the effect of histone deacetylase (HDAC) inhibitors (HDACis) on somatostatin type-2 receptor (SSTR2) expression and [111In]In-/[177Lu]Lu-DOTA-TATE uptake in vitro and in vivo. Materials and methods: The human cell lines NCI-H69 (small-cell lung carcinoma) and BON-1 (pancreatic neuroendocrine tumor) were treated with HDACis (i.e. entinostat, mocetinostat (MOC), LMK-235, CI-994 or panobinostat (PAN)), and SSTR2 mRNA expression levels and [111In]In-DOTA-TATE uptake were measured. Furthermore, vehicle- and HDACi-treated NCI-H69 and BON-1 tumor-bearing mice were injected with radiolabeled DOTA-TATE followed by biodistribution studies. Additionally, SSTR2 and HDAC mRNA expression of xenografts, and of NCI-H69, BON-1, NCI-H727 (human pulmonary carcinoid) and GOT1 (human midgut neuroendocrine tumor) cells were determined. Key findings: HDACi treatment resulted in the desired effects in vitro. However, no significant increase in tumoral DOTA-TATE uptake was observed after HDACi treatment in NCI-H69 tumor-bearing animals, whereas tumoral SSTR2 mRNA and/or protein expression levels were significantly upregulated after treatment with MOC, CI-994 and PAN, i.e. a maximum of 2.1- and 1.3-fold, respectively. Analysis of PAN-treated BON-1 xenografts solely demonstrated increased SSTR2 mRNA expression levels. Comparison of HDACs and SSTR2 expression in BON-1 and NCI-H69 xenografts showed a significantly higher expression of 6/11 HDACs in BON-1 xenografts. Of these HDACs, a significant inverse correlation was found between HDAC3 and SSTR2 expression (Pearson r = −0.92) in the studied cell lines. Significance: To conclude, tumoral uptake levels of radiolabeled DOTA-TATE were not enhanced after HDACi treatment in vivo, but, depending on the applied inhibitor, increased SSTR2 expression levels were observed.</p
Daylight Saving Time and Spontaneous Deliveries: A Case–Control Study in Italy
(1) Background: Although the current literature shows that daylight saving time (DST) may play a role in human health and behavior, this topic has been poorly investigated with reference to Obstetrics. The aim of this case–control study was to evaluate whether DST may influence the number of spontaneous deliveries. (2) Methods: A low-risk pregnancy cohort with spontaneous onset of labor (n = 7415) was analyzed from a single Italian region for the period 2016–2018. Primary outcome was the number of spontaneous deliveries. Secondary outcomes were: gestational age at delivery, type and time of delivery, use of analgesia, birth weight, and 5-min Apgar at delivery. We compared the outcomes in the two weeks after DST (cases) to the two weeks before DST (controls). (3) Results: Data showed no significant difference between the number of deliveries occurring before and after DST (Chi-square = 0.546, p = 0.46). Vaginal deliveries at any gestational age showed no statistical difference between the two groups (Chi-square = 0.120, p = 0.73). There were no significant differences in the secondary outcomes, as well. (4) Conclusions: DST has neither a significant impact on the number of deliveries nor on the obstetric variables investigated by this study
Ultrasound-Responsive Cavitation Nuclei for Therapy and Drug Delivery
Therapeutic ultrasound strategies that harness the mechanical activity of cavitation nuclei for beneficial tissue bio-effects are actively under development. The mechanical oscillations of circulating microbubbles, the most widely investigated cavitation nuclei, which may also encapsulate or shield a therapeutic agent in the bloodstream, trigger and promote localized uptake. Oscillating microbubbles can create stresses either on nearby tissue or in surrounding fluid to enhance drug penetration and efficacy in the brain, spinal cord, vasculature, immune system, biofilm or tumors. This review summarizes recent investigations that have elucidated interactions of ultrasound and cavitation nuclei with cells, the treatment of tumors, immunotherapy, the blood–brain and blood–spinal cord barriers, sonothrombolysis, cardiovascular drug delivery and sonobactericide. In particular, an overview of salient ultrasound features, drug delivery vehicles, therapeutic transport routes and pre-clinical and clinical studies is provided. Successful implementation of ultrasound and cavitation nuclei-mediated drug delivery has the potential to change the way drugs are administered systemically, resulting in more effective therapeutics and less-invasive treatments
Left ventricular mass increases with deteriorating glucose tolerance, especially in women: Independence of increased arterial stiffness or decreased flow-mediated dilation - The Hoorn Study
OBJECTIVE - Type 2 diabetes and impaired glucose metabolism (IGM) are associated with an increased cardiovascular disease (CVD) risk. Increased left ventricular mass (LVM) is thought to increase CVD risk through several unfavorable cardiac changes. Type 2 diabetes and IGM are associated with increased LVM, but the underlying mechanism is unclear. We investigated the association between glucose tolerance status (GTS) and LVM and explored whether any such association could be mediated through increased arterial stiffness, impaired endothelial function, or the presence of atherosclerosis. RESEARCH DESIGN AND METHODS - We used ultrasound to measure LVM, carotid and femoral stiffness, carotid-femoral transit time, and flow-mediated vasodilation (FMD) and tonometry to estimate compliance and augmentation index. The study population (n = 780) consisted of 287 individuals with normal glucose metabolism (NGM), 179 with IGM, and 314 with type 2 diabetes, and the mean age was 68.4 years. RESULTS - In women, after adjusting for age, height, BMI, and mean arterial pressure, LVM increased significantly with deteriorating GTS (LVM 157 g in NGM, 155 g in IGM, and 169 g in type 2 diabetes, P for trend <0.018). Additional adjustment for arterial stiffness, FMD, or the presence of atherosclerosis did not materially alter the results, even though these variables were significantly associated with both GTS and LVM. Indexes of hyperglycemia/-insulinemia or insulin resistance explained at most 7% of the association between GTS and LVM. In men, no statistically significant associations were observed. CONCLUSIONS - Our data expand the conceptual view of the pathogenesis of GTS-related changes in LVM because we show that the increase in LVM in women is independent of increased arterial stiffness, impaired FMD, or the presence of atherosclerosis. In addition, we show that this increase in LVM is only minimally explained by indexes of hyperglycemia/-insulinemia or insulin resistance. Our data may, in part, explain the increased CVD risk seen in women with deteriorating GTS
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