Publications by authors named "N A A Barbosa"

199 Publications

Toxicology and pharmacology of synthetic organoselenium compounds: an update.

Arch Toxicol 2021 04 1;95(4):1179-1226. Epub 2021 Apr 1.

Laboratório de Síntese, Reatividade e Avaliação Farmacológica E Toxicológica de Organocalcogênios, Centro de Ciências Naturais E Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, CEP 97105-900, Brazil.

Here, we addressed the pharmacology and toxicology of synthetic organoselenium compounds and some naturally occurring organoselenium amino acids. The use of selenium as a tool in organic synthesis and as a pharmacological agent goes back to the middle of the nineteenth and the beginning of the twentieth centuries. The rediscovery of ebselen and its investigation in clinical trials have motivated the search for new organoselenium molecules with pharmacological properties. Although ebselen and diselenides have some overlapping pharmacological properties, their molecular targets are not identical. However, they have similar anti-inflammatory and antioxidant activities, possibly, via activation of transcription factors, regulating the expression of antioxidant genes. In short, our knowledge about the pharmacological properties of simple organoselenium compounds is still elusive. However, contrary to our early expectations that they could imitate selenoproteins, organoselenium compounds seem to have non-specific modulatory activation of antioxidant pathways and specific inhibitory effects in some thiol-containing proteins. The thiol-oxidizing properties of organoselenium compounds are considered the molecular basis of their chronic toxicity; however, the acute use of organoselenium compounds as inhibitors of specific thiol-containing enzymes can be of therapeutic significance. In summary, the outcomes of the clinical trials of ebselen as a mimetic of lithium or as an inhibitor of SARS-CoV-2 proteases will be important to the field of organoselenium synthesis. The development of computational techniques that could predict rational modifications in the structure of organoselenium compounds to increase their specificity is required to construct a library of thiol-modifying agents with selectivity toward specific target proteins.
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http://dx.doi.org/10.1007/s00204-021-03003-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012418PMC
April 2021

Efficiency of lysine utilization by growing meat quail.

Poult Sci 2021 Apr 23;100(4):101012. Epub 2021 Jan 23.

Center of Agrarian and Environmental Sciences, Federal University of Maranhão, Campus Chapadinha, Chapadinha, Maranhão, Brazil.

The objective of present study was to estimate the efficiency of lysine utilization by meat quail of 21 to 35 d of age. A total of 500 meat quails were distributed in a completely randomized design in a 2 × 5 factorial arrangement, with 2 sexes (male and female) and 5 digestible lysine levels (0.714, 0.816, 0.918, 1.020, and 1.122%) and 5 replications of 10 birds each. The variables studied were feather-free body weight (FFBW), feed intake (FI), lysine intake (LysI), feather-free body protein deposition (FFBPD), feather-free body lysine deposition (FFBLysD), feather-free body fat deposition (FFBFatD), feather weight (FW), feather protein deposition, feather lysine deposition, and feather fat deposition. The FFBW, FFBPD, FFBLysD, and FFBFatD were regressed as a function of LysI for each sex to estimate the efficiency of lysine utilization in the feather-free body (ELysFFB), and the individual equations were compared. In addition, a multiple regression without intercept was also used to estimate the ELysFFB and in feathers (ELysF) individually. To compare the ELysFFB obtained by the different methods, the t-statistic was used. There was no effect on sex × lysine level interactions for any variable. The females showed higher FFBW (5.07%) and FFBFatD (26.23%) than males. All variables increased with the level of dietary lysine, with the exception of FI, FW, and the deposition of nutrients within them. The ELysFFB values obtained by simple linear regression and multiple linear regression were 48.0 and 44.6%, respectively. As there was no difference in the efficiencies estimated by the different methodologies, the best estimate of ELysFFB was 46.3%, that is, the average. The best estimate of ELysF was 18.1%, obtained by multiple linear regression.
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http://dx.doi.org/10.1016/j.psj.2021.01.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921006PMC
April 2021

Intra- and interrater reliability of Fugl-Meyer Assessment of Lower Extremity early after stroke.

Braz J Phys Ther 2020 Dec 17. Epub 2020 Dec 17.

Institute of Neuroscience and Physiology, Clinical Neuroscience, Rehabilitation Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address:

Background: The Fugl-Meyer Assessment of Lower Extremity (FMA-LE) is a widely used and recommended scale for evaluation of post-stroke motor impairment. However, the reliability of the scale has only been established by using parametric statistical methods, which ignores the ordinal properties of the scale.

Objective: To determined intra- and inter-rater reliability of the FMA-LE at item and summed score level early after stroke.

Methods: Sixty patients (mean age 65.9 years, median FMA-LE 29 points) admitted to the hospital due to stroke were included. The FMA-LE was simultaneously, but independently, scored by three experienced and trained physical therapists randomly assigned into pairs, on two consecutive days, between 4 to 9 days post stroke. A rank-based statistical method for paired ordinal data was used to assess the level of agreement and systematic and random disagreements.

Results: The item-level reliability was high (percentage of agreement [PA] ≥75%). Two items (ankle dorsiflexion during flexor synergy and normal reflex activity) showed some systematic disagreement in intrarater analysis. A satisfactory intrarater reliability (PA ≥70%) was reached for all summed scores when a 1- or 2-point difference was accepted between ratings.

Conclusion: The FMA-LE is a reliable tool for assessment of motor impairment both within and between raters early after stroke. The scale can be recommended not only for use in Spanish speaking countries, but also internationally. A unified international use of FMA-LE would allow comparison of stroke recovery outcomes worldwide and thereby potentially improve the quality of stroke rehabilitation.
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http://dx.doi.org/10.1016/j.bjpt.2020.12.002DOI Listing
December 2020

Premature mortality due to cervical cancer: study of interrupted time series.

Rev Saude Publica 2020 14;54:139. Epub 2020 Dec 14.

Universidade Federal Fluminense. Faculdade de Medicina. Niterói, RJ, Brasil.

Objective: To verify the effect of the Pact for Health on premature mortality (30-69 years) attributed to cervical cancer in Brazil and its macroregions, using interrupted time series analysis.

Methods: Segmented regression was used to assess "change in level" and "change in trend" in premature mortality rates attributed to cervical cancer considering the post-Pact period (2010-2018), controlling by the pre-Pact period (1998-2006). Understanding the triennium 2007-2009 as essential for the adoption and implementation of the policy, it was excluded from the main modeling, but assessed in the sensitivity analysis.

Results: From 1998 to 2018, there were more than 119,000 deaths due to cervical cancer in women aged 30 to 69 years in Brazil. The Northern region experienced the highest rates (> 20 per 100,000). Comparing with baseline (1998-2006), segmented regression showed a progressive increase in changing trend from cervical cancer deaths in Brazil as a whole (coefficient = 0.513; 95%CI 0.430 to 0.596) and in the Southeast region (coefficient = 0.515; 95%CI 0.358 to 0.674), South region (coefficient = 0.925; 95%CI 0.642 to 1.208), and Midwest region (coefficient = 0.590; 95%CI 0.103 to 1.077). The Northeast region presented the most promising effects with immediate reduction in change level (-0.635; 95%CI -1.177 to -0.092) and progressive reduction in the changing trend of premature deaths (coefficient= -0.151; 95%CI -0.231 to -0.007).

Conclusions: Premature mortality rates due to cervical cancer are high in Brazil and its macroregions. This interrupted time series was not able to reveal the effectiveness of initiatives related to the Pact for Health on premature deaths from cervical cancer nationally and in all macroregions equally. The best results are restricted to the Northeast region.
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http://dx.doi.org/10.11606/s1518-8787.2020054002528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703528PMC
January 2021

Langerhans cell histiocytosis in the occipital condyle: a case study and a brief review of the literature.

BMJ Case Rep 2020 Dec 12;13(12). Epub 2020 Dec 12.

Oncologia Pediátrica, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Lisboa, Portugal.

We present a case study of a 5-year-old patient, who presented with left-sided torticollis. Due to persistence of problems, a CT and an MRI were made showing a single osteolytic lesion centred on right occipital condyle. After an open biopsy, histology confirmed it to be Langerhans cell histiocytosis (LCH). Torticollis or restricted range of motion is a presenting feature in 76% of children with LCH with cervical involvement. There remains much debate on the best treatment strategy. The clinical and radiological outcomes of the case study presented on this article support the treatment of LCH with chemotherapy in cases with solitary involvement of the occipital condyle.
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http://dx.doi.org/10.1136/bcr-2020-235630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735094PMC
December 2020

Successful Unilateral Surgical Approach to Internal Globus Pallidus and Ventral Intermediate Nucleus of the Thalamus in 3 Cases of Myoclonus-Dystonia Syndrome.

Stereotact Funct Neurosurg 2020 Nov 26:1-6. Epub 2020 Nov 26.

Movement Disorders and Neurodegenerative Diseases Unit, Hospital Civil de Guadalajara "Fray Antonio Alcalde", University of Guadalajara, Guadalajara, Mexico,

Surgical approaches of internal globus pallidus (GPi) and ventral intermediate thalamic nucleus (Vim) have been used to treat different movement disorders. Three subjects with myoclonus-dystonia syndrome were surgically treated, one of them with GPi and Vim stimulation, while radiofrequency ablation of these structures was performed in the other 2 subjects. Surgical approach of both targets was performed simultaneously on each subject. Mean follow-up was of 33.3 months (22-48 months), the Unified Myoclonus Rating Scale action myoclonus (AM), functional tests (FT), patient questionnaire (PQ) sub-scores, and the Unified Dystonia Rating Scale (UDRS) were used during assessments. Improvement in all scales were seen 6 months after surgery (AM: 74%, FT: 60%, PQ: 63%, UDRS: 65%), and this benefit persisted throughout follow-up (AM: 61%, FT:62%, PQ: 65%, UDRS: 86%). No adverse events were noticed. Simultaneous unilateral procedures of GPi and Vim by either stimulation or ablation techniques improve both motor and functional scores in myoclonus-dystonia syndrome.
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http://dx.doi.org/10.1159/000511715DOI Listing
November 2020

Oropouche Virus Infects, Persists and Induces IFN Response in Human Peripheral Blood Mononuclear Cells as Identified by RNA PrimeFlow™ and qRT-PCR Assays.

Viruses 2020 07 21;12(7). Epub 2020 Jul 21.

Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil.

(OROV) is an emerging arbovirus with a high potential of dissemination in America. Little is known about the role of peripheral blood mononuclear cells (PBMC) response during OROV infection in humans. Thus, to evaluate human leukocytes susceptibility, permissiveness and immune response during OROV infection, we applied RNA hybridization, qRT-PCR and cell-based assays to quantify viral antigens, genome, antigenome and gene expression in different cells. First, we observed OROV replication in human leukocytes lineages as THP-1 monocytes, Jeko-1 B cells and Jurkat T cells. Interestingly, cell viability and viral particle detection are maintained in these cells, even after successive passages. PBMCs from healthy donors were susceptible but the infection was not productive, since neither antigenome nor infectious particle was found in the supernatant of infected PBMCs. In fact, only viral antigens and small quantities of OROV genome were detected at 24 hpi in lymphocytes, monocytes and CD11c cells. Finally, activation of the Interferon (IFN) response was essential to restrict OROV replication in human PBMCs. Increased expression of type I/III IFNs, ISGs and inflammatory cytokines was detected in the first 24 hpi and viral replication was re-established after blocking IFNAR or treating cells with glucocorticoid. Thus, in short, our results show OROV is able to infect and remain in low titers in human T cells, monocytes, DCs and B cells as a consequence of an effective IFN response after infection, indicating the possibility of leukocytes serving as a trojan horse in specific microenvironments during immunosuppression.
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http://dx.doi.org/10.3390/v12070785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411765PMC
July 2020

Sequesterpene Lactones Isolated from a Brazilian Cerrado Plant ( spp. as Anti-Proliferative Compounds, Characterized by Functional and Proteomic Analysis, are Candidates for New Therapeutics in Glioblastoma.

Int J Mol Sci 2020 07 1;21(13). Epub 2020 Jul 1.

Protein Chemistry Center and Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP 14049-900, Brazil.

Gliomas are responsible for more than 60% of all primary brain tumors. Glioblastoma multiforme (GBM), a grade IV tumor (WHO), is one of the most frequent and malignant gliomas. Despite two decades of advances in the discovery of new markers for GBM, the chemotherapy of choice falls to temozolomide after surgery and radiotherapy, which are not enough to increase the survival of patients to more than 15 months. It is urgent to discover new anti-glioma compounds. Many compounds derived from natural products have been used in the development of anti-tumor drugs. In this work, we have screened six low molecular weight sesquiterpene lactones, isolated from spp., and studied their function as anti-proliferative agents against GBM strains. We demonstrated that two of them, goyazensolide and lychnofolide, were effective in reducing cell viability, preventing the formation of anchorage-dependent colony and were able to pass through a mimetic blood-brain barrier making them candidates for glioma therapy, being more potent than temozolomide, according to in vitro assays for the cell lines tested. Proteomic analysis revealed a number of altered proteins involved in glycolytic metabolism and cellular catabolism.
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http://dx.doi.org/10.3390/ijms21134713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369765PMC
July 2020

Gene expression patterns of in vivo-derived sheep blastocysts is more affected by vitrification than slow freezing technique.

Cryobiology 2020 08 15;95:110-115. Epub 2020 Jun 15.

Faculdade de Veterinária, Universidade Federal Fluminense, Av. Vital Brasil Filho, 64, CEP 24230-340, Niterói, RJ, Brazil. Electronic address:

Transfer of fresh sheep embryos frequently results in higher pregnancy rate compared to cryopreserved ones, possibly due to a failure in the communication between the cryopreserved embryo and the endometrium during pre-implantation and pregnancy establishment. Thus, this study assessed the effect of sheep embryo cryopreservation (slow freezing or vitrification) on embryo survival rate and expression of genes related to trophectoderm differentiation (CDX2), pluripotency maintenance (NANOG), cell proliferation (TGFB1), mitochondrial activity (NRF1) and apoptosis (BAX and BCL2). Superovulation (n = 32 ewes) was performed and embryos were transcervically collected. One hundred good quality (Grade I and II) embryos were allocated into three groups: fresh embryos (CTL; n = 15), slow freezing (SF; n = 42) or vitrification (VT; n = 43). After thawing/warming, three pools of five blastocysts per group were used for RT-qPCR; the remaining 55 embryos were cultured in vitro in SOFaa medium at 38.5 °C and 5% CO (SF: n = 27 and VT: n = 28). Survival rate of SF and VT were, respectively, 29.6% (8/27) and 14.2% (4/28) at 24 h; and 48.1% (13/27) and 32.1% (9/28) at 48 h (P > 0.05). Only CDX2 was affected (up-regulated, P < 0.05) in both groups compared to CTL. The BAX transcript was upregulated in VT, compared to SF group. The VT increased (P < 0.05) the expression of all genes, except for NANOG and NRF1, when compared to the CTL. In conclusion, although in vitro survival was similar between techniques, VT led to increased changes in blastocyst gene expression compared to CTL and SF.
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http://dx.doi.org/10.1016/j.cryobiol.2020.05.009DOI Listing
August 2020

Modulation of redox and insulin signaling underlie the anti-hyperglycemic and antioxidant effects of diphenyl diselenide in zebrafish.

Free Radic Biol Med 2020 10 13;158:20-31. Epub 2020 Jun 13.

Programa de Pós-graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria, Avenida Roraima, 1000, 97105-900, Santa Maria, RS, Brazil. Electronic address:

The organic selenium compound diphenyl diselenide (DD) has been recognized as an antioxidant and neuroprotective agent, exerting an anti-hyperglycemic effect in experimental models of diabetes. However, the precise mechanisms involved in the protection are unclear. Using the zebrafish (Danio rerio) as a model organism, here we investigated biomarkers underlying the protective effects of DD against hyperglycemia, targeting in a transcriptional approach the redox and insulin-signaling pathway. Fish were fed on a diet containing DD (3 mg/kg) for 74 days. In the last 14 days, they were exposed to a 111 mM glucose solution to induce a hyperglycemic state. DD reduced blood glucose levels as well as normalized the brain mRNA transcription of four insulin receptors-coding genes (Insra1, Insra2, Insrb1, Insrb2), which were down-regulated by glucose. DD alone caused an up-regulation of relative mRNA transcription in both Insra receptors and glucose transporter 3 genes. DD counteracted hyperglycemia-induced lipid peroxidation, protein and thiol depletion. Along with the decreased activity of antioxidant enzymes SOD and GPx, the brain of hyperglycemic fish presented a reduction in mRNA transcription of FoxO3A, FoxO3B, Nrf2, GPx3A, SOD1, and SOD2 genes. Besides normalizing the transcriptional levels, DD caused an up-regulation of relative mRNAs that encode Nrf2, FoxO1A, FOXO3A, GPx4A, PTP1B, AKT and SelP. Collectively, our findings suggest that the antioxidant and anti-hyperglycemic actions of DD in a zebrafish diabetes model are likely associated with the regulation of the oxidative stress resistance and the insulin-signaling pathway and that could be related to the modulation at mRNA level of two important transcription factors, Nrf2 and FoxO.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.06.002DOI Listing
October 2020

Excisional goniotomy with Kahook Dual Blade in a patient with glaucoma secondary to Transthyretin Amyloidosis.

Am J Ophthalmol Case Rep 2020 Sep 20;19:100750. Epub 2020 May 20.

Grippo Glaucoma and Cataract Center, Buenos Aires, Argentina.

Purpose: To report for the first time the successful use of the Kahook Dual Blade excisional goniotomy technique in a patient with Transthyretin Amyloidosis.

Patient And Methods: The Kahook Dual Blade is a single use ab interno trabeculectomy device that removes the trabecular meshwork reducing aqueous humor outflow resistance. A patient with Transthyretin Amyloidosis underwent this procedure.

Results: Ab interno goniotomy with Kahook Dual Blade was a successful surgical solution to reduce intraocular pressure in a patient with Transthyretin Amyloidosis secondary glaucoma controlling IOP in association with topical hypotensors for at least 6 months.

Conclusions: Ab interno goniotomy with Kahook Dual Blade is a surgical option for this type of glaucoma, that treats the main site of aqueous outflow resistance in this pathology with the advantage of being minimally invasive.
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http://dx.doi.org/10.1016/j.ajoc.2020.100750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267710PMC
September 2020

Genetic Variability of Ceraeochrysa cincta, Ceraeochrysa claveri, and Ceraeochrysa cubana (Neuroptera: Chrysopidae) Populations in Agroecosystems of Southeast Brazil.

Environ Entomol 2020 06;49(3):765-775

Instituto de Biociências, Letras e Ciências Exatas (Ibilce), Universidade Estadual Paulista (Unesp), Campus São José do Rio Preto, SP, Brazil.

The species of the genus Ceraeochrysa, known as green lacewings or trash-carriers, are widely distributed along the Americas and its islands. In Brazil, 28 species are found, including Ceraeochrysa cincta (Schneider), Ceraeochrysa claveri (Navás), and Ceraeochrysa cubana (Hagen). These species are recorded on many crops, where they are often used for biological control. For this use, knowledge of the genetic features of the species is extremely important because they are associated to the species' ability to withstand different conditions in new environments, such as variations of temperature and presence of pathogens. However, little is known about the genetic features of Ceraeochrysa species. Here, we analyze and compare the distribution of the genetic variability of C. cincta, C. claveri, and C. cubana in agroecosystem populations of southeast Brazil. We found a high genetic diversity in each of the three species, and no strong genetic structure was detected, such that genetic diversity is broadly shared among the crops and localities analyzed. We can conclude that there was a high gene flow among the sampled Ceraeochrysa populations (natural or driven by anthropic action) since the exchange of seedlings among crops can lead to the distribution of the specimens.
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http://dx.doi.org/10.1093/ee/nvaa021DOI Listing
June 2020

Accessing the transcriptional status of selenoproteins in skin cancer-derived cell lines.

J Trace Elem Med Biol 2020 Jul 27;60:126476. Epub 2020 Feb 27.

Laboratory of Insect Virology, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, Santa Maria, RS, 97105-900, Brazil. Electronic address:

Background: Selenoproteins are selenocysteine (Sec)-containing proteins that exhibit numerous physiological functions, mainly antioxidative activities. Studies have suggested that several human selenoproteins play an important role in tumor initiation and progression, including melanoma.

Methods: Using RNA-seq data set from Sequence Reads Archive (SRA) experiments published at the National Center for Biotechnology Information (NCBI), we determined and compared the transcriptional levels of the 25 selenoproteins-coding sequences found in 16 human-derived melanoma cell lines and compared to four melanocyte controls.

Results: 15 selenoprotein-coding genes were found to be expressed in melanoma and normal melanocyte cells, and their mRNA levels varied among the cell lines. All melanoma cells analyzed with BRAF or NRAS mutations presented upregulated levels of SELENOI, TXNRD1, and SELENOT transcripts and downregulated levels of SELENOW and SELENON transcripts in comparison with melanocytes controls. Moreover, SELENOW, SELENON, SELENOI, TXNRD1, and SELENOT-coding transcripts were affected when BRAF-mutated A375 cells were treated with CPI203, A771726 or Vorinostat drugs.

Conclusion: Our results indicate that melanoma cells can modify, in a different manner, the selenoprotein transcript levels, as a possible mechanism to control tumor progression. We suggest that the usage of diet and supplements containing selenium should be carefully used for patients with melanoma.
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http://dx.doi.org/10.1016/j.jtemb.2020.126476DOI Listing
July 2020

Comparative effects of two heat acclimation protocols consisting of high-intensity interval training in the heat on aerobic performance and thermoregulatory responses in exercising rats.

PLoS One 2020 21;15(2):e0229335. Epub 2020 Feb 21.

Physical Effort Laboratory, Graduate Program in Physical Education, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.

Acclimation resulting from low- to moderate-intensity physical exertion in the heat induces several thermoregulatory adaptations, including slower exercise-induced increases in core body temperature. However, few studies have investigated the thermoregulatory adaptations induced by high-intensity interval training (HIIT) protocols. Thus, the present study aimed to compare the adaptations in rats' thermoregulatory parameters and aerobic performance observed after two different heat acclimation regimens consisting of HIIT protocols performed in a hot environment. Twenty-three adult male Wistar rats were initially subjected to an incremental-speed exercise at 32°C until they were fatigued and then randomly assigned to one of the following three heat acclimation strategies: passive heat exposure without any exercise (untrained controls-UN; n = 7), HIIT performed at the maximal aerobic speed (HIIT100%; n = 8) and HIIT performed at a high but submaximal speed (HIIT85%; n = 8). Following the two weeks of interventions, the rats were again subjected to a fatiguing incremental exercise at 32°C, while their colonic temperature (TCOL) was recorded. The workload performed by the rats and their thermoregulatory efficiency were calculated. After the intervention period, rats subjected to both HIIT protocols attained greater workloads (HIIT100%: 313.7 ± 21.9 J vs. HIIT85%: 318.1 ± 32.6 J vs. UN: 250.8 ± 32.4 J; p < 0.01) and presented a lower ratio between the change in TCOL and the distance travelled (HIIT100%: 4.95 ± 0.42°C/km vs. HIIT85%: 4.33 ± 0.59°C/km vs. UN: 6.14 ± 1.03°C/km; p < 0.001) when compared to UN rats. The latter finding indicates better thermoregulatory efficiency in trained animals. No differences were observed between rats subjected to the two HIIT regimens. In conclusion, the two HIIT protocols induce greater thermoregulatory adaptations and performance improvements than passive heat exposure. These adaptations do not differ between the two training protocols investigated in the present study.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229335PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034902PMC
May 2020

Nasal Valve Insufficiency in Dermatologic Surgery.

Dermatol Surg 2020 07;46(7):904-911

All authors are affiliated with the Department of Dermatology, Mayo Clinic, Rochester, Minnesota.

Background: Few publications have addressed nasal valve (NV) insufficiency as a complication of Mohs micrographic surgery.

Objective: To comprehensively review the literature and further characterize the causes, prevalence, evaluation, and management of NV insufficiency as it relates to cutaneous oncology.

Materials And Methods: A PubMed search was completed to identify articles related to the NV in the context of Mohs micrographic surgery, cutaneous oncology, and reconstruction.

Results: Nasal valve insufficiency may occur during tumor removal and/or reconstruction. Defect size larger than 1 cm; location on the ala, sidewall, or alar crease; lack of structural support; and poorly planned flaps are the main risk factors for NV insufficiency. Several surgical techniques have been described to avoid and correct this complication.

Conclusion: Nasal valve insufficiency may be an underrecognized and underreported complication of Mohs micrographic surgery. Nasal valve insufficiency may be identified with relatively simple tests. Knowledge of NV anatomy and preoperative function assessment is essential. Recognition of this potential complication and awareness of its prevention and management may decrease morbidity in patients undergoing cutaneous surgery.
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http://dx.doi.org/10.1097/DSS.0000000000002310DOI Listing
July 2020

Anthropogenic litter on Brazilian beaches: Baseline, trends and recommendations for future approaches.

Mar Pollut Bull 2020 Feb 29;151:110842. Epub 2020 Jan 29.

Núcleo de Ecologia Aquática e Pesca da Amazônia, Universidade Federal do Pará, Belém, PA, Brazil.

Beaches are fundamental habitats that regulate the functioning of several coastal processes and key areas contributing to national and local budgets. In this study we provide the first large-scale systematic survey of anthropogenic litter on Brazilian beaches, covering a total of 35 degrees of latitude, recording the litter type, its use and size. Plastic comprised the most abundant litter type, followed by cigarette butts and paper. Small pieces (<5 cm) were dominant among litter size-classes and food-related use was associated to most litter recorded types. Generalized additive models showed that proximity to estuarine run-offs was the main driver to beach litter accumulation, reinforcing river drainages as the primary route of litter coastal pollution. Also, the Clean-Coast Index evidenced there was not a pattern of beach litter pollution among regions, which denotes that actions regarding marine pollution must be taken by all state governances of the country.
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http://dx.doi.org/10.1016/j.marpolbul.2019.110842DOI Listing
February 2020

Cyclophosphamide in Drosophila promotes genes and transposable elements differential expression and mitochondrial dysfunction.

Comp Biochem Physiol C Toxicol Pharmacol 2020 Apr 23;230:108718. Epub 2020 Jan 23.

PPG Genética e Biologia Molecular, Univ. Fed. do Rio Grande do Sul, Porto Alegre, Brazil; Dep de Bioquímica e Biologia Molecular, Univ. Fed. de Santa Maria, Santa Maria, Brazil. Electronic address:

Cyclophosphamide (CPA) is an alkylating agent used for cancer chemotherapy, organ transplantation, and autoimmune disease treatment. Here, mRNA sequencing and high-resolution respirometry were performed to evaluate the alterations of Drosophila melanogaster gene expression fed with CPA under acute (0.1 mg/mL, for 24 h) and chronic (0.05 mg/mL, for 35 days) treatments. Differential expression analysis was performed using Cufflinks-Cuffdiff, DESeq2, and edgeR software. CPA affected genes are involved in several biological functions, including stress response and immune-related pathways, oxi-reduction and apoptotic processes, and cuticle and vitelline membrane formation. In particular, this is the first report of CPA-induced mitochondrial dysfunction caused by the downregulation of genes involved with mitochondria constituents. CPA treatment also changed the transcription pattern of transposable elements (TEs) from the gypsy and copia superfamilies. The results presented here provided evidence of CPA mitochondrial toxicity mechanisms and that CPA can modify TEs transcription in Drosophila flies.
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http://dx.doi.org/10.1016/j.cbpc.2020.108718DOI Listing
April 2020

Design, synthesis, antileishmanial, and antifungal biological evaluation of novel 3,5-disubstituted isoxazole compounds based on 5-nitrofuran scaffolds.

Arch Pharm (Weinheim) 2020 Feb 16;353(2):e1900241. Epub 2019 Dec 16.

LASQUIM-Laboratório de Síntese e Química Medicinal, FACFAN-Faculdade de Ciências Farmacêuticas, Alimentos e Nutrição, Universidade Federal do Mato Grosso do Sul (UFMS), Campo Grande, Brazil.

Nineteen 3,5-disubstituted-isoxazole analogs were synthesized based on nitrofuran scaffolds, by a [3 + 2] cycloaddition reaction between terminal acetylenes and 5-nitrofuran chloro-oxime. The compounds were obtained in moderate to very good yields (45-91%). The antileishmanial activity was assayed against the promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. Alkylchlorinated compounds 14p-r were active on both the promastigote and amastigote forms, with emphasis on compound 14p, which showed strong activity against the amastigote form (IC  = 0.6 μM and selectivity index [SI] = 5.2). In the alkyl series, compound 14o stands out with an IC  = 8.5 μM and SI = 8.0 on the amastigote form. In the aromatic series, the most active compounds were those containing electron-donor groups, such as trimethoxy isoxazole 14g (IC  = 1.2 μM and SI = 20.2); compound 14h, with IC  = 7.0 μM and SI = 6.1; and compound 14j containing the 4-SCH group, with IC  = 5.7 μM and SI = 10.2. In addition, the antifungal activity of 19 nitrofuran isoxazoles was evaluated against five strains of Candida (C. albicans, C. parapsilosis, C. krusei, C. tropicalis, and C. glabrata). Eleven isoxazole derivatives were active against C. parapsilosis, and compound 14o was found to be the most active (minimal inhibitory concentration [MIC] = 3.4 μM) for this strain. Compound 14p was active against all the strains tested, with an MIC = 17.5 μM for C. glabrata, lower than that of the fluconazole used as the reference drug.
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http://dx.doi.org/10.1002/ardp.201900241DOI Listing
February 2020

Down-regulation of TUFM impairs host cell interaction and virulence by Paracoccidioides brasiliensis.

Sci Rep 2019 11 20;9(1):17206. Epub 2019 Nov 20.

Faculdade de Ciências Farmacêuticas, UNESP - Univ Estadual Paulista, Campus Araraquara, Departamento de Análises Clínicas, Laboratório de Micologia Clinica, São Paulo, Brazil.

The genus Paracoccidioides consist of dimorphic fungi geographically limited to the subtropical regions of Latin America, which are responsible for causing deep systemic mycosis in humans. However, the molecular mechanisms by which Paracoccidioides spp. causes the disease remain poorly understood. Paracoccidioides spp. harbor genes that encode proteins involved in host cell interaction and mitochondrial function, which together are required for pathogenicity and mediate virulence. Previously, we identified TufM (previously known as EF-Tu) in Paracoccidioides brasiliensis (PbTufM) and suggested that it may be involved in the pathogenicity of this fungus. In this study, we examined the effects of downregulating PbTUFM using a silenced strain with a 55% reduction in PbTUFM expression obtained by antisense-RNA (aRNA) technology. Silencing PbTUFM yielded phenotypic differences, such as altered translation elongation, respiratory defects, increased sensitivity of yeast cells to reactive oxygen stress, survival after macrophage phagocytosis, and reduced interaction with pneumocytes. These results were associated with reduced virulence in Galleria mellonella and murine infection models, emphasizing the importance of PbTufM in the full virulence of P. brasiliensis and its potential as a target for antifungal agents against paracoccidioidomycosis.
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http://dx.doi.org/10.1038/s41598-019-51540-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868139PMC
November 2019

Methyl and Ethylmercury elicit oxidative stress and unbalance the antioxidant system in Saccharomyces cerevisiae.

Chem Biol Interact 2020 Jan 28;315:108867. Epub 2019 Oct 28.

Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. Electronic address:

Methylmercury (MeHg) and Ethylmercury (EtHg) are toxic to the central nervous system. Human exposure to MeHg and EtHg results mainly from the consumption of contaminated fish and thimerosal-containing vaccines, respectively. The mechanisms underlying the toxicity of MeHg and EtHg are still elusive. Here, we compared the toxic effects of MeHg and EtHg in Saccharomyces cerevisiae (S. cerevisiae) emphasizing the involvement of oxidative stress and the identification of molecular targets from antioxidant pathways. Wild type and mutant strains with deleted genes for antioxidant defenses, namely: γ-glutamylcysteine synthetase, glutathione peroxidase, catalase, superoxide dismutase, mitochondrial peroxiredoxin, cytoplasmic thioredoxin, and redox transcription factor Yap1 were used to identify potential pathways and proteins from cell redox system targeted by MeHg and EtHg. MeHg and EtHg inhibited cell growth, decreased membrane integrity, and increased the granularity and production of reactive species (RS) in wild type yeast. The mutants were predominantly less tolerant of mercurial than wild type yeast. But, as the wild strain, mutants exhibited higher tolerance to MeHg than EtHg. Our results indicate the involvement of oxidative stress in the cytotoxicity of MeHg and EtHg and reinforce S. cerevisiae as a suitable model to explore the mechanisms of action of electrophilic toxicants.
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http://dx.doi.org/10.1016/j.cbi.2019.108867DOI Listing
January 2020

Assessing the toxicant effect of spontaneously volatilized 4-vinylcyclohexane exposure in nymphs of the lobster cockroach nauphoeta cinerea.

Environ Toxicol Pharmacol 2019 Nov 16;72:103264. Epub 2019 Sep 16.

Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Programa de Pós-graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria, RS, Brazil. Electronic address:

Vinylcyclohexene (VCH) is an environmental contaminant well known for its ovotoxicant effects in several organisms. However, the mechanisms underlying the toxicity of VCH as well as its harmful effects toward other organs are until unclear. In this work, we assess some endpoint signals of toxicity induced by volatilized VCH exposure using nymphs of the lobster cockroach Nauphoeta cinerea. Nymphs were exposed to VCH via inhalation for 70 days. The levels of volatilized VCH were quantified by headspace gas chromatography and the concentration varied between 3.41 and 7.03 nmol/μl. VCH inhalation caused a reduction of 35% in the survival rate of the exposed animals. Nymphs exposed to volatilized VCH for 35 and 70 days had a reduction in the body weight gain of 1.8- and 2.6-fold, respectively with a reduction in dissected head, fat body, and maturing reproductive organs. The exposure did not change water consumption, excepting on the 20th day (with a 3-fold change) and decreased the food intake significantly. Regarding biochemical markers, we found that the activity of GST from the dissected organs was increased by volatilized VCH after both 35 and 70 days of exposure. The fat body presented the most prominent GST activity especially after 35 days of exposure with 1.6-fold higher than the control group. Exposure also caused an increase in RS levels in the fat body of 1.35-fold and 1.47-fold after 35 and 70 days, respectively and did not affect the activity of the AChE from the head. Our findings support the harmful impact of volatilized VCH inhalation, highlighting the cockroach N.cinerea as a valuable insect model to investigate environmental toxicants.
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http://dx.doi.org/10.1016/j.etap.2019.103264DOI Listing
November 2019

Trypanosoma cruzi and hematospermia.

Int Urol Nephrol 2019 Dec 18;51(12):2201-2202. Epub 2019 Sep 18.

Hospital Universitário Professor Edgard Santos/Federal University of Bahia, Rua Dr. Augusto Viana, S/n-Canela, Salvador, BA, 40110-060, Brazil.

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http://dx.doi.org/10.1007/s11255-019-02279-yDOI Listing
December 2019

Osteochondritis Dissecans of the Lateral Femoral Trochlea Healing after Isolated Medial Patellofemoral Ligament Reconstruction: A Case Report.

Malays Orthop J 2019 Jul;13(2):35-37

Department of Orthopedics and Traumatology, Hospital Pedro Hispano, Matosinhos, Portugal.

We report on a 12 years old female patient who had been diagnosed with patellofemoral instability - recurrent dislocation and anterior knee pain. Radiologic evaluation further revealed osteochondritis dissecans (OCD) of the lateral femoral trochlea. She underwent surgical procedure with isolated medial patellofemoral ligament reconstruction, no surgical procedure was done to the OCD lesion. Postoperatively, there was clinical improvement of patellofemoral instability, with radiological evidence of healing of the OCD lesion. Isolated realignment procedures such as medial patellofemoral ligament reconstruction may be associated with spontaneous healing of osteochondritis dissecans of the lateral femoral trochlea.
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http://dx.doi.org/10.5704/MOJ.1907.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702980PMC
July 2019

Intra- and inter-rater reliability of Fugl-Meyer Assessment of Upper Extremity in stroke.

J Rehabil Med 2019 Oct;51(9):652-659

Human Movement Department, National University of Colombia, , Bogota, Colombia.

Objective: The Fugl-Meyer Assessment of Upper Extremity (FMA-UE) is recommended for evaluation of sensorimotor impairment post stroke, but the item-level reliability of the scale is unknown. The study aims to determine intra- and inter-rater reliability of the FMA-UE at item-, subscale- and total score level in patients with early subacute stroke.

Design: Intra/inter-rater reliability.

Subjects: Sixty consecutively included patients with stroke (mean age 65.9 years) admitted to Central Military Hospital of Colombia, Bogota.

Methods: Two physiotherapists scored FMA-UE independently on 2 consecutive days within 10 days post stroke. A rank-based statistical method for paired ordinal data was used to assess the level of agreement, systematic and random disagreements.

Results: Systematic disagreements either in position or concentration were detected in 4 items of the shoulder section. The item level intra- and inter-rater agreement was high (79100%). The 70% agreement was also reached for the subscales and the total score when 13-point difference was accepted.

Conclusion: The FMA-UE is reliable both within and between raters in patients with stroke in the early subacute phase. A wider international use of FMA-UE will allow comparison of stroke recovery between regions and countries and thereby potentially improve the quality of care and rehabilitation in persons with stroke worldwide.
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http://dx.doi.org/10.2340/16501977-2590DOI Listing
October 2019

Effect of isoxazole derivatives of tetrahydrofuran neolignans on intracellular amastigotes of Leishmania (Leishmania) amazonensis: A structure-activity relationship comparative study with triazole-neolignan-based compounds.

Chem Biol Drug Des 2019 12 12;94(6):2004-2012. Epub 2019 Sep 12.

LASQUIM - Laboratório de Síntese e Química Medicinal, Faculdade de Ciências Farmacêuticas, Alimentos e Nutrição, Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil.

Isoxazole analogues derived from the neolignans veraguensin, grandisin, and machilin G were previously synthesized with different substitution patterns through the bioisosterism strategy. These compounds were tested on intracellular amastigotes of Leishmania (Leishmania) amazonensis; the derivatives proved to be active against intracellular amastigotes, with IC values ranging from 0.4 to 25 μM. The most active analogues were 4', 14', 15', and 18', with IC values of 0.9, 0.4, 0.7, and 1.4 μM, respectively, showing high selectivity indexes (SI = 277.0; 625.0; 178.5 and 357.1). Overall, the isoxazole analogues did not induce nitric oxide (NO) production by infected cells; there was no evidence that NO influences the antileishmanial mechanism of action, except for compound 4'. Trimethoxy groups as substituents seemed to be critical for antileishmanial activity. The SAR study demonstrated that the isoxazole compounds were more active than 1,2,3-triazole compounds with the same substitution pattterns, demonstrating the importance of the bioisosterism strategy in drug design.
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http://dx.doi.org/10.1111/cbdd.13609DOI Listing
December 2019

Verrucous carcinoma of the upper lip: An exuberant presentation in a patient with other synchronous lesions.

Indian J Dermatol Venereol Leprol 2020 Mar-Apr;86(2):230

Department of Dermatovenereology, Garcia de Orta Hospital, Almada, Portugal.

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http://dx.doi.org/10.4103/ijdvl.IJDVL_529_17DOI Listing
December 2020

Intraparenchymal cystic lesion after Deep Brain Stimulation surgery: An unusual complication.

Parkinsonism Relat Disord 2019 07 11;64:354-355. Epub 2019 May 11.

Programa de Parkinson y Movimientos Anormales, Hospital de Clínicas "José de San Martín", Av. Córdoba 2351 (C1121ABJ), Ciudad Autónoma de Buenos Aires, Argentina.

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http://dx.doi.org/10.1016/j.parkreldis.2019.05.016DOI Listing
July 2019

Adalimumab-Related Dental Implant Infection.

J Oral Maxillofac Surg 2019 Jun 30;77(6):1165-1169. Epub 2019 Jan 30.

Attending Surgeon, Division of Oral and Maxillofacial Surgery, Allegheny General Hospital, Pittsburgh, PA.

We present an adalimumab-related dental implant surgical-site infection. A 55-year-old patient with a history of twice-weekly adalimumab subcutaneous injections for ulcerative colitis underwent mandibular extractions and placement of 5 immediate dental implants. She experienced intraoral purulent drainage from all 5 dental implant sites with submental and submandibular space infections 2 weeks after surgery. Treatment consisted of extraoral incision and drainage of involved fascial spaces, removal of all mandibular dental implants, and debridement of necrotic mandibular bone. She went on to heal uneventfully. In individuals taking adalimumab, severe infection with loss of implants and bone may develop.
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http://dx.doi.org/10.1016/j.joms.2019.01.033DOI Listing
June 2019

Genotoxic and mutagenic assessment of spinosad using bioassays with Tradescantia pallida and Drosophila melanogaster.

Chemosphere 2019 May 31;222:503-510. Epub 2019 Jan 31.

Institute of Biotechnology, Federal University of Uberlândia, Campus Umuarama, 38900-402, Uberlândia, Minas Gerais, Brazil.

Spinosad (SPN) is a naturally-occurring insecticide obtained from the fermentation process of the actinomycete Saccharopolyspora spinosa. Owing to the larvicidal action, the compound has been used in the control of Aedes aegypti. As a new insecticide commercially available in the market, few data are reported on genotoxic effects in non-target organisms. The objective of the present study was to evaluate the mutagenic effect of SPN through the Micronucleus Test in Tradescantia pallida (Trad-MCN) and using the mutation and somatic recombination test in Drosophila melanogaster (SMART). At the Trad-MCN, after acclimatization (24 h), T. pallida stems were submitted to chronic treatment with SPN at concentrations of 0.156; 0.312; 0.625; 1.25 and 2.5 g/L solution for 24 h, followed by a recovery period. In SMART, considering the third stage larvae, offspring resulting from the ST and HB crossing were placed on chronic treatment (48 h) with 0.039; 0.078 and 0.156 μg/mL of SPN solution. No mutagenic effect was observed at any of the evaluated concentrations in SMART. Additionally, SPN is more toxic after metabolism via CYP6A2 (cytochrome P450) in D. melanogaster. However, SPN at the concentrations of 0.625; 1.25 and 2.5 g/L was able to induce high frequency of micronuclei in T. pallida. Under the experimental conditions of T. pallida in the present study, SPN caused genotoxic activity.
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http://dx.doi.org/10.1016/j.chemosphere.2019.01.182DOI Listing
May 2019

Methylglyoxal disturbs the expression of antioxidant, apoptotic and glycation responsive genes and triggers programmed cell death in human leukocytes.

Toxicol In Vitro 2019 Mar 15;55:33-42. Epub 2018 Nov 15.

Departamento de Bioquímica e Biologia Molecular, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria (UFSM), Campus Universitário - Camobi, 97105-900 Santa Maria, RS, Brazil. Electronic address:

Methylglyoxal (MG) is a α-dycarbonyl compound derived mainly from glycolysis, whose accumulation is harmful for cells and tissues. Here, we evaluated the cytotoxic effects induced by MG in leukocytes after an acute exposure, measuring as endpoints of toxicity some markers of oxidative stress and programmed cell death. Human leukocytes were isolated and incubated with MG at concentrations ranging from 0.1 to 10 mM for 2.5 h, and subsequently prepared for assays based in flow cytometry, gene expression and immunoreactivity profile. The cells exposed to higher concentrations of MG had significant loss of viability, increased reactive species (RS) production and apoptosis/necrosis rate. These phenomena were accompanied by morphological changes (increased size and granularity) and disruption in mRNA expression of antioxidant, apoptotic and glycation-responsive genes, particularly: Nrf2 (Nuclear factor (erythroid-derived 2)-like 2), SOD1 (CuZn-superoxide dismutase), SOD2 (Mn-superoxide dismutase), GSR (glutathione-S-reductase), BAX (BAX-associated X protein), BCL-2 (BCL-2-associated X protein), AIF (apoptosis inducing factor), GLO-1 (glyoxalase-1) and RAGE (receptor for advanced glycation end products). The mRNA expression of CASP 9 and CASP 3 (caspase-9 and 3) as well as the immunoreactivity of proteins were not changed by MG. Collectively, our data provide evidence that MG activates programmed cell death pathways in leukocytes and that this effect seems to be associated with disturbances in cell redox signaling.
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http://dx.doi.org/10.1016/j.tiv.2018.11.001DOI Listing
March 2019