Context:
Calcitonin (CT) is a sensitive marker of medullary thyroid carcinoma (MTC) and is used for primary diagnosis and follow-up after thyroidectomy. However, persistently elevated CT is observed ...even after complete surgical removal without evidence of a recurrent or persistent tumor.
Objective:
To investigate the presence of assay interference in the serum CT of MTC patients who are apparently without a structural disease.
Patients and Methods:
We studied three index MTC cases for CT assay interference and 14 patients with metastatic MTC. The CT level was measured using an immunofluorometric assay. Screening for assay interference was performed by determination of CT levels before and after serum treatment with polyethylene glycol. Additionally, samples were analyzed by chromatography on ultra-performance liquid chromatography and protein A-Sepharose.
Results:
Patients with biochemical and structural disease showed CT mean recovery of 84.1% after polyethylene glycol treatment, whereas patients suspected of interference showed recovery from 2–7%. The elution profile on UPLC showed that the immunometric CT from these three patients behaved like a high molecular mass aggregate (>300 kDa). Additionally, when these samples were applied to the protein A-Sepharose, CT immunoreactivity was retained on the column and was only released after lowering the pH.
Conclusions:
For the first time, our results show the presence of a novel pitfall in the CT immunoassay: “macrocalcitonin.” Its etiology, frequency, and meaning remain to be defined, but its recognition is of interest and can help clinicians avoid unnecessary diagnostic investigations and treatment during the follow-up of MTC.
We describe herein our results on the synthesis and biological properties in Caenorhabditis elegans of a range of 4-organylsulfenyl-7-chloroquinolines. This class of compounds have been easily ...synthesized in high yields by direct reaction of 4,7-dichloroquinoline with organylthiols using DMSO as solvent at room temperature under air atmosphere and tolerates a range of substituents in the organylsulfenyl moiety. We have performed a toxicological and pharmacological screening of the synthesized 4-organylsulfenyl-7-chloroquinolines in vivo in C. elegans acutely exposed to these compounds, under per se and stress conditions. Hence, we determined the lethal dose 50% (LD50), in order to choose a nonlethal concentration (10 μM) and verified that at that concentration some of the compounds depicted protective action against the induced damage inflicted by paraquat, a superoxide generator. Two compounds (3c and 3h) reduced the toxicity inflicted by paraquat above survival, reproduction and longevity of the worms, at least in part, by reducing the reactive oxygen species (ROS) generated by the toxicant exposure. Besides, these compounds increased the quantities of superoxide dismutase (SOD-3::GFP) and catalase (CTL-1,2,3::GFP), antioxidant enzymes. We concluded that the protective effects of the compounds observed in this study might have been a hormetic response dependent of the transcriptional factor DAF-16/FOXO, causing a non-lethal oxidative stress that protects against the subsequently damage induced by paraquat.
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•Sulfur-containing quinolines were directly synthesized under mild reaction conditions.•Compounds attenuated the oxidative damage on survival, reproduction and longevity through a hormetic response.•Compounds modulated the DAF-16/FOXO pathway.•DAF-16/FOXO modulation possibly up-regulated SOD-3::GFP and CTL-1,2::GFP lowering the ROS levels.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
3.
Novel immunoassay for TSH measurement in rats Alves, Thalita G; Melo, Maria Clara de C; Kasamatsu, Teresa S ...
Archives of Endocrinology and Metabolism,
09/2017, Volume:
61, Issue:
5
Journal Article
Open access
Measuring thyroid hormones is an important aspect for the study of metabolism and for monitoring diseases in both human and animal models. The traditional method for hormone measurement in rats is ...the radioimmunoassay (RIA). However, the RIA is associated with some practical disadvantages, including the use of radioactive material, the need for specialized equipment and expert staff, the short shelf-life of kits according to the half-life of the radioisotope and high costs. The objective of this study was to develop a new cost-effective method for measuring TSH levels in rats that avoids the use of radioactive material. We developed an in-house competitive immunoassay using a reference standard, polyclonal antibody produced in rabbits and biotinylated antigen. This method was tested in 64 Wistar rats that were divided into a control group (n = 41) and a group with hypothyroidism (n = 23). Our assay demonstrated an analytical sensitivity of 0.24 ng/mL (n = 12) and an intra-assay coefficient of variation (CV) of 8.9% for sera with TSH levels of 1.5 ng/mL and 13.2% for sera with TSH levels of 17.5 ng/mL (n = 14). The inter-assay CV was 13.5% for sera with TSH levels of 1.4 ng/mL and 14.5% for TSH levels of 18.2 ng/mL (n = 5). The analysis of mean TSH levels in control rats (5.06 ± 0.5701) and hypothyroid rats (51.09 ± 5.136) revealed a statistically significant difference (p < 0.001) between the groups. This method showed good sensitivity, can be automated and is low-cost compared with RIA. Our method offers a viable alternative for TSH measurement in rats.
Cetacean morbillivirus (CeMV) causes illness and death in cetaceans worldwide; the CeMV strains circulating in the Southern Hemisphere are poorly known. We detected a pilot whale CeMV strain in 3 ...short-finned pilot whales (Globicephala macrorhynchus) stranded in Brazil during July-October 2020. Our results confirm this virus circulates in this species.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The exploitation of phonon–polaritons in nanostructured materials offers a pathway to manipulate infrared (IR) light for nanophotonic applications. Notably, hyperbolic phonon–polaritons (HP2) in ...polar bidimensional crystals have been used to demonstrate strong electromagnetic field confinement, ultraslow group velocities, and long lifetimes (up to ∼12 ps). Here we present nanobelts of α-phase molybdenum trioxide (α-MoO3) as a low-dimensional medium supporting HP2 modes in the mid- and far-IR ranges. Through real-space nanoimaging techniques with synchrotron and tunable laser IR light, we observe HP2 Fabry-Perot resonances that demonstrate distinct anisotropic propagation and frequency dependence. We remark an anisotropic propagation that critically depends on the frequency range. Our findings are supported by the convergence of experiment, theory, and numerical simulations. Our work shows that the low dimensionality of natural nanostructured crystals, like α-MoO3 nanobelts, provides an attractive platform to study polaritonic light–matter interactions and offers appealing cavity properties that could be harnessed in future designs of compact nanophotonic devices.
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IJS, KILJ, NUK, PNG, UL, UM
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•A direct and selective multicomponent strategy is described.•The reaction is catalysed by CuBr as a cheap, nontoxic and easy to handle salt.•The ...1,3,5-triaryl-4-(organylselanyl)-1H-pyrazoles were obtained in good yields.
We describe herein our results for the multicomponent synthesis of 1,3,5-triaryl-4-(organylselanyl)pyrazoles by copper-catalyzed cyclocondensation and a direct CH bond selenation reaction of arylhydrazines, chalcones and diorganyl diselenides using catalytic amount of CuBr in acetic acid as solvent at reflux temperature. This methodology proved to be simple and efficient to furnish a range of 4-(organylselanyl)-1H-pyrazoles in moderate to good yields.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We describe herein an efficient protocol to synthesize selanyl‐substituted pyrazoles by cyclocondensation and copper‐catalyzed direct CH bond selenation reactions. The products were obtained in ...moderate to excellent yields by the one‐pot multicomponent reactions of hydrazines, 1,3‐diketones and diorganyl diselenides, using catalytic amounts of copper bromide and bipyridine. These reactions tolerated a range of substituents in the starting materials and proved to be an efficient methodology for combinatorial synthesis of new selenium‐containing pyrazoles with potential applications in biological studies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The involvement of miRNA in mesial temporal lobe epilepsy (MTLE) pathogenesis has increasingly become a focus of epigenetic studies. Despite advances, the number of known miRNAs with a consistent ...expression response during epileptogenesis is still small. Addressing this situation requires additional miRNA profiling studies coupled to detailed individual expression analyses. Here, we perform a miRNA microarray analysis of the hippocampus of Wistar rats 24 hours after intra-hippocampal pilocarpine-induced Status Epilepticus (H-PILO SE). We identified 73 miRNAs that undergo significant changes, of which 36 were up-regulated and 37 were down-regulated. To validate, we selected 5 of these (10a-5p, 128a-3p, 196b-5p, 352 and 324-3p) for RT-qPCR analysis. Our results confirmed that miR-352 and 196b-5p levels were significantly higher and miR-128a-3p levels were significantly lower in the hippocampus of H-PILO SE rats. We also evaluated whether the 3 miRNAs show a dysregulated hippocampal expression at three time periods (0h, 24h and chronic phase) after systemic pilocarpine-induced status epilepticus (S-PILO SE). We demonstrate that miR-128a-3p transcripts are significantly reduced at all time points compared to the naïve group. Moreover, miR-196b-5p was significantly higher only at 24h post-SE, while miR-352 transcripts were significantly up-regulated after 24h and in chronic phase (epileptic) rats. Finally, when we compared hippocampi of epileptic and non-epileptic humans, we observed that transcript levels of miRNAs show similar trends to the animal models. In summary, we successfully identified two novel dysregulated miRNAs (196b-5p and 352) and confirmed miR-128a-3p downregulation in SE-induced epileptogenesis. Further functional assays are required to understand the role of these miRNAs in MTLE pathogenesis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Since its first detection in the Caribbean in late 2013, chikungunya virus (CHIKV) has affected 51 countries in the Americas. The CHIKV epidemic in the Americas was caused by the CHIKV-Asian ...genotype. In August 2014, local transmission of the CHIKV-Asian genotype was detected in the Brazilian Amazon region. However, a distinct lineage, the CHIKV-East-Central-South-America (ECSA)-genotype, was detected nearly simultaneously in Feira de Santana, Bahia state, northeast Brazil. The genomic diversity and the dynamics of CHIKV in the Brazilian Amazon region remains poorly understood despite its importance to better understand the epidemiological spread and public health impact of CHIKV in the country.
We report a large CHIKV outbreak (5,928 notified cases between August 2014 and August 2018) in Boa vista municipality, capital city of Roraima's state, located in the Brazilian Amazon region. We generated 20 novel CHIKV-ECSA genomes from the Brazilian Amazon region using MinION portable genome sequencing. Phylogenetic analyses revealed that despite an early introduction of the Asian genotype in 2015 in Roraima, the large CHIKV outbreak in 2017 in Boa Vista was caused by an ECSA-lineage most likely introduced from northeastern Brazil. Epidemiological analyses suggest a basic reproductive number of R0 of 1.66, which translates in an estimated 39 (95% CI: 36 to 45) % of Roraima's population infected with CHIKV-ECSA. Finally, we find a strong association between Google search activity and the local laboratory-confirmed CHIKV cases in Roraima.
This study highlights the potential of combining traditional surveillance with portable genome sequencing technologies and digital epidemiology to inform public health surveillance in the Amazon region. Our data reveal a large CHIKV-ECSA outbreak in Boa Vista, limited potential for future CHIKV outbreaks, and indicate a replacement of the Asian genotype by the ECSA genotype in the Amazon region.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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