Chagas disease is one of the most important endemic parasitic diseases in Latin America. In its chronic phase, progression to cardiomyopathy has high morbidity and mortality. The persistence of a ...normal electrocardiogram (ECG) provides a similar prognosis to that of a non-diseased population. Benznidazole (BNZ) is the only drug with trypanocidal action available in Brazil.
A group of 310 patients with chronic Chagas disease who had normal ECGs at the first medical visit performed before 2002 were included. There were 263 patients treated with BNZ and 47 untreated. The follow-up period was 19.59 years. Univariate analyses showed that those treated were younger and predominantly male. As many as 79.08% of those treated and 46.81% of those untreated continued with normal electrocardiograms (p <0.0001). The occurrence of electrocardiographic abnormalities and relevant clinical events (heart failure, stroke, total mortality, and cardiovascular death) was less prevalent in treated patients (p <0.001, p: 0.022, p: 0.047 respectively). In multivariate analyses, the parasiticide treatment was an independent variable for persistence of a normal ECG pattern, which was an independent variable in the prevention of significant clinical events. The immunofluorescence titers decreased with the parasitological treatment. However, the small number of tests in untreated patients did not allow the correlation of the decrease of these titers with electrocardiographic alterations.
These data suggest that treatment with benznidazole prevents the occurrence of electrocardiographic alterations. On the other hand, patients who develop ECG abnormalities present with more significant clinical events.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Prediction of pathogenicity of rare copy number variations (CNVs), a genomic alteration known to contribute to the etiology of autism spectrum disorder (ASD), represents a serious limitation to ...interpreting genetic tests, particularly for genetic counseling purposes. Chromosomal microarray analysis (CMA) was conducted in a unique collection of 144 Brazilian individuals with ASD of strong European and African ancestries. Rare CNVs were detected in 39 patients: 41 of unknown significance (VUS), four pathogenic and one likely pathogenic CNVs (clinical yield of 4.1%; 5/122). Based on gene content and recurrence in three large cohorts a Brazilian neurodevelopmental disorder cohort, the autism MSSNG cohort, and the Canadian‐based Centre for Applied Genomics microarray database, this work strengthened the pathogenicity of 14 genes (FAT1, CAMK4, BIRC6, DPP6, CSMD1, CTNNA3, CDH8/CDH11, CDH13, OR1C1, CNTN6, CNTNAP4, FGF2 and PTPRN2) within 14 CNVs. Notably, enrichment of cell adhesion proteins to ASD etiology was identified (p < 0.05), highlighting the importance of these gene families in the etiology of ASD.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Oral transmission of acute Chagas disease is an emerging public health concern. This study aimed to detect insect fragments in experimentally contaminated food, by comparing triatomines with other ...insects.
Food samples were experimentally contaminated with insects, processed to recover their fragments by light filth, and analyzed by microscopy and Polymerase Chain Reaction (PCR).
Morphological differences between coleopteran and triatomine insects were observed in microscopic images. PCR was efficient in amplifying Triatominae DNA in the experimentally contaminated food.
This methodology could be utilized by food analysts to identify possible insect contamination in food samples.
Chagas disease, caused by Trypanosoma cruzi affects about 6–8 million people worldwide. Although transmission by triatomine insects has been controlled, other means of transmission maintain the ...infection. These forms of transmission are responsible for introducing Chagas disease in other non-endemic countries of the world. Thus, Chagas disease, nowadays is a worldwide health problem. In Brazil, acai pulp and sugarcane juice have been associated with Chagas disease outbreaks. The difficulties in isolation of the parasite from foods are hampering source tracking which could allow the confirmation of an implicated food commodity in these outbreak investigations. To address this scientific gap, we evaluated the performance of real-time PCR (qPCR) for detecting T. cruzi in acai pulp and sugarcane juice. All experiments were performed with acai pulp and sugarcane juice samples contaminated with different concentrations of T. cruzi. In assays with qPCR, the results showed that the ideal procedure for T. cruzi identification in acai pulp and sugarcane juice consisted of: i. centrifugation; ii. DNA extraction with a commercial kit for stool matrix; and iii. qPCR using a specific molecular marker for T. cruzi. The seeding in LIT medium of experimentally contaminated foods was effective in detecting the parasitic load by qPCR. The efficacy of qPCR was also verified testing food samples crushed with infected Triatomines. In conclusion, this methodology can be used to perform rapid diagnosis in outbreaks, facilitating measures in disease control.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Approximately seven to eight million people worldwide have Chagas disease. In Brazil, benznidazole is the most commonly used active drug against Trypanosoma cruzi; however, its efficacy is limited, ...and side effects are frequent. Recent studies suggest that amiodarone may be beneficial in the treatment of this disease, by exerting anti-T. cruzi action. This study evaluated changes in T. cruzi cell count in in vitro cultures subjected to different doses of benznidazole, amiodarone, and their combination.
T. cruzi (Y strain) cultures containing approximately 100,000 cells were treated with either 100mg, 50mg, 25mg, 12.5mg, or 10mg of benznidazole, amiodarone, or their combination. On the 4th day, cell count was compared to the baseline data.
On the 4th day, no parasites were observed in any of the treated cultures.
Benznidazole and amiodarone were equally effective in eliminating T. cruzi in culture. The combination of the two drugs was also equally effective, but our data cannot demonstrate synergism, as similar results were obtained when the drugs were tested individually or in combination. It is suggested that this study be repeated with other T. cruzi strains to determine whether similar results can be obtained again.
The aim of this study was to synthesize and characterize polymeric porous scaffolds associated with different calcium phosphates (CaP) and Mesenchymal Stem Cells (MSC) for regenerative dentistry ...application. Chitosan-Xanthan Scaffolds (CX) were associated with 5% of the two CaP types, Hydroxyapatite (HA) and Brushite (BS). For advanced cell therapies, the scaffolds were associated with MSC. The scaffold structures were characterized by X Ray Diffraction (DRX), Fourier Transformed Infrared (FTIR), Thermogravimetric Analysis (TGA), Scanning Electron Microscopy analysis (SEM) and the compressive strength. The in vitro Cytotoxicity was performed and the in vivo Biocompatibility by histomorphometry and inflammatory cells number count. XRD showed the amorphous phase of CX and main peaks of the CaP phases in the HA and BS scaffolds. FTIR showed the amide I and II bands, characteristic of Chitosan, and carboxyl group, characteristic of Xanthan. PO4 bands were found in CaP scaffolds. SEM showed pores and CaP fillers incorporated and adhered to the polymer in the CX-HA, CX-BS, CX-HA + MSC and CX-BS + MSC. Compressive strength and Modulus of Elasticity analysis exhibited higher values for CX-BS scaffolds, followed by CX-HA and CX. All scaffolds showed acceptable cells viability after 24 h and 48 h; however, the CX scaffolds showed higher cell viability in 48 h. CX-BS produced significantly higher inflammatory cells number after 7 and 30 days of implantation. After 60 days of implantation, CX + MSC and CX-HA + MSC showed the lowest inflammatory cells number. The CaP improved the mechanical properties of scaffolds but decreased the cell viability. MSCs improved the inflammatory response after 60 days.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite the severity and the high prevalence of depression and anxiety and the efforts that have been done to improve their treatment, the available pharmacotherapy still has several limitations. ...Therefore, the investigation of novel agents and the characterization of the molecular signaling pathways underlying their effects are needed. The organoselenium compound 3-(4-chlorophenyl)selanyl-1-methyl-1H-indole (CMI) has emerged as a promising antidepressant and anxiolytic molecule in several animal models of depression through the modulation of neuroinflammation and oxidative stress. In light of this, the present study aimed to dive into the mechanism of action of CMI in ameliorating anhedonic- and anxiogenic-like behaviors induced by repeated corticosterone administration in mice. A single administration of CMI (1 mg/kg, i.g.) abrogated the behavioral alterations induced by corticosterone in the open field test, splash test, and elevated plus maze test. Additionally, CMI treatment decreased the levels of reactive species and lipid peroxidation in the plasma of corticosterone-treated mice and normalized the expression of GR, BDNF, synaptophysin, GSK-3β, Nrf2, and IDO in the hippocampi of stressed mice. Noteworthy, the pre-treatment of mice with LY294002 (PI3K inhibitor) and rapamycin (mTOR inhibitor) abrogated the anti-anhedonic- and anxiolytic-like effects elicited by CMI in corticosterone-treated mice, while ZnPP (HO-1 inhibitor) counteracted the anxiolytic-like effect of CMI. These findings suggest that CMI might ameliorate behavioral and biochemical alterations in the depression-anxiety comorbidity induced by corticosterone, highlighting the potential of CMI as a possible adjuvant therapy.
•CMI ameliorated chronic corticosterone-induced anhedonic- and anxiogenic-like behaviors.•CMI modulated the expression of GR, BDNF, synaptophysin, GSK-3β, Nrf2, and IDO.•Inhibition of PI3K/mTOR pathway abolished the behavioral effects of CMI.•The anxiolytic-like effect of CMI is abolished in the presence of a HO-1 inhibitor.•An in silico analysis predicted that CMI might interact with p38 MAPK and GSK-3β.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background/Purpose The purpose of the study was to describe the initial experience with a novel approach to the surgical treatment of progressive familial intrahepatic cholestasis (PFIC), ...avoiding the creation of a permanent stoma. Methods Two teenaged patients, aged 15 and 17 years, underwent partial internal biliary diversion to treat incontrollable pruritus associated with PFIC. The surgical technique involved the creation of an isolated jejunal conduit, anastomosed proximally in a terminolateral fashion to the gallbladder and distally to the ascending colon. This operation combines the advantages of partially diverting the biliary flow from the enterohepatic cycle, avoiding an external biliary fistula. In one of the patients, this technique was used as a primary procedure, whereas in the other, a previous partial external diversion was converted to an internal diversion. Results Both patients had complete resolution of their pruritus and normalization of hepatic laboratory tests. One of the patients developed a mild choleretic diarrhea that can be controlled with eventual use of cholestyramine. No complications were observed related to this operation. Conclusions Biliary diversion appears to be a very attractive surgical option for the treatment of PFIC in children with a normal gallbladder. Long-term follow-up is necessary to evaluate late results and eventual complications of this approach.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Rationale and objectives
Stress-induced alterations in oxidative and inflammatory parameters have been implicated in the pathophysiology of mood disorders. Based on the antioxidant and ...anti-inflammatory properties of the selenium-containing compound 3-((4-chlorophenyl)selanyl)-1-methyl-1
H
-indole (CMI), we assessed its ability to reverse depression-like behavioral alterations, neuroinflammation, and oxidative imbalance induced by acute restraint stress.
Methods
Mice submitted to restraint for 240 min received CMI (1 or 10 mg/kg, orally) 10 min after the end of the stress induction. Behavioral and biochemical tests were carried out after further 30 min.
Results
Restraint-induced depression-like behavior in the tail suspension test (TST), splash test, and new object exploration test was reversed by CMI. None of the treatments evoked locomotor alteration. In addition, CMI abrogated restraint-induced increases in plasma levels of corticosterone and in markers of oxidative stress and impaired superoxide dismutase and catalase activity in the prefrontal cortex (PFC) and hippocampus (HC). CMI also blocked stress-induced downregulation of mRNA levels of glucocorticoid receptor and brain-derived neurotrophic factor and upregulation of nuclear factor kappa B, inducible nitric oxide synthase, tumor necrosis alpha, indoelamine-2,3-dioxygenase, and glycogen synthase kinase 3 beta in PFC and HC.
Conclusions
These preclinical results indicate that administration of selenium-containing compounds might help to treat depression associated with inflammation and oxidative stress.
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DOBA, EMUNI, FIS, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
This research aimed at evaluating optimal conditions to obtain value-added metabolites, such as bio-CH4, by co-digesting swine manure and food waste diluted in domestic sewage. The assays were ...carried out in batches using the statistical methods of Rotational Central Composite Design (RCCD) and Surface Response to evaluate the ranges of food waste (1.30–9.70 gTS.L−1), pH (6.16–7.84) and granular Upflow Anaerobic Sludge Blanket sludge as inoculum (2.32–5.68 gTS.L−1), besides about 250 mL of swine manure in 500 mL Duran flasks. According to the RCCD matrix, bio-CH4 yields among 600.6 ± 60.1 and 2790.0 ± 112.0 mL CH4 gTS.L−1 were observed, besides the maximum CH4 production rate between 0.4 ± 0.5 and 49.7 ± 2.0 mL CH4 h−1 and λ between ≤0.0 and 299.3 ± 4.5 h. In the validation assay, the optimal conditions of 9.98 gTS.L−1 of food waste, pH adjusted to 8.0 and 2.20 gTS.L−1 of inoculum were considered, and the bio-CH4 yield obtained (5640.79 ± 242.98 mL CH4 gTS.L−1 or also 5201.83 ± 224.07 mL CH4 gTVS.L−1) was 11.3 times higher than in assays before optimization (499.3 ± 16.0 mL CH4 gTS.L−1) with 5 gTS.L−1 of food waste, 3 gTS.L−1 of inoculum and pH 7.0. Besides, the results observed about the energetic balance of the control and validation assays highlight the importance of process optimization, as this condition was the only one with energy supply higher than the energy required for its operation, exceeding max consumption sevenfold. Based on the most dominant microorganisms (Methanosaeta, 31.06%) and the metabolic inference of the validation assay, it could be inferred that the acetoclastic methanogenesis was the predominant pathway to CH4 production.
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•Co-digestion of food waste and swine manure were beneficial to CH4 production.•Optimization increased CH4 yield 11.3 times compared to unoptimized assays.•The highest yield was 5640.79 mL CH4 gTS.L−1 under optimized conditions.•The main metabolites observed were HBu (351.4 mg.L−1) and HAc (399.3 mg.L−1).•Methanosaeta was the main archaea under optimized conditions (31.06%).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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