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1.
Hum Genomics ; 17(1): 50, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37287057

RESUMO

BACKGROUND: The use of molecular biomarkers for COVID-19 remains unconclusive. The application of a molecular biomarker in combination with clinical ones that could help classifying aggressive patients in first steps of the disease could help clinician and sanitary system a better management of the disease. Here we characterize the role of ACE2, AR, MX1, ERG, ETV5 and TMPRSS2 for trying a better classification of COVID-19 through knowledge of the disease mechanisms. METHODS: A total of 329 blood samples were genotyped in ACE2, MX1 and TMPRSS2. RNA analyses were also performed from 258 available samples using quantitative polymerase chain reaction for genes: ERG, ETV5, AR, MX1, ACE2, and TMPRSS2. Moreover, in silico analysis variant effect predictor, ClinVar, IPA, DAVID, GTEx, STRING and miRDB database was also performed. Clinical and demographic data were recruited from all participants following WHO classification criteria. RESULTS: We confirm the use of ferritin (p < 0.001), D-dimer (p < 0.010), CRP (p < 0.001) and LDH (p < 0.001) as markers for distinguishing mild and severe cohorts. Expression studies showed that MX1 and AR are significantly higher expressed in mild vs severe patients (p < 0.05). ACE2 and TMPRSS2 are involved in the same molecular process of membrane fusion (p = 4.4 × 10-3), acting as proteases (p = 0.047). CONCLUSIONS: In addition to the key role of TMPSRSS2, we reported for the first time that higher expression levels of AR are related with a decreased risk of severe COVID-19 disease in females. Moreover, functional analysis demonstrates that ACE2, MX1 and TMPRSS2 are relevant markers in this disease.


Assuntos
COVID-19 , Feminino , Humanos , COVID-19/genética , Enzima de Conversão de Angiotensina 2/genética , SARS-CoV-2/genética , Marcadores Genéticos , Bases de Dados Factuais , Serina Endopeptidases/genética , Proteínas de Resistência a Myxovirus
2.
World J Surg ; 48(4): 855-862, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38353292

RESUMO

BACKGROUND: Isolated perforations of hollow viscus (HV) represent less than 1% of injuries in blunt abdominal trauma (BAT). When they do present, they are generally due to high-impact mechanisms in the segments of the intestine that are fixed. The aim of this study is to determine the incidence of major HV injuries in BAT at the "Dr. Domingo Luciani" General Hospital (HDL), and address the literature gap regarding updated HV perforations following BAT, especially in low-income settings. METHODS: A retrospective review was conducted on the medical records of patients admitted to our trauma center with a diagnosis of complicated BAT with HV perforation over 14 years. RESULTS AND DISCUSSION: Seven hundred sixty-one patients were admitted under the diagnosis of BAT. Of them, 36.79% underwent emergency surgical resolution, and 6.04% had HV perforation as an operative finding. Almost half (44.44%) of these cases presented as a single isolated injury, while the remaining were associated with other intra-abdominal organ injuries. The most common lesions were Grade II-III jejunum and Grade I transverse colon, affecting an equal proportion of patients at 13.33%. In recent years, an increased incidence of HV injuries secondary to BAT has been observed. Despite this, in many cases, the diagnosis is delayed, so even in the presence of negative diagnostic studies, the surgical approach based on the trauma mechanism, hemodynamic status, and systematic reevaluation of the polytraumatized patient should prevail.


Assuntos
Traumatismos Abdominais , Perfuração Intestinal , Ferimentos não Penetrantes , Humanos , Centros de Traumatologia , Ferimentos não Penetrantes/epidemiologia , Ferimentos não Penetrantes/cirurgia , Ferimentos não Penetrantes/complicações , Traumatismos Abdominais/epidemiologia , Traumatismos Abdominais/cirurgia , Traumatismos Abdominais/complicações , Jejuno , Perfuração Intestinal/cirurgia , Estudos Retrospectivos
3.
Vet Surg ; 53(4): 684-694, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38135927

RESUMO

OBJECTIVE: To describe near-infrared fluorescence (NIRF) for assessment of gastric viability and describe NIRF's influence on the surgeon's operative strategy in dogs with gastric dilatation and volvulus (GDV). STUDY DESIGN: Prospective clinical trial. ANIMALS: Twenty dogs with GDV and 20 systemically healthy dogs. METHODS: Following gastric derotation, the surgeon's subjective assessment of gastric viability was recorded prior to near-infrared imaging. Changes in the surgeon's initial assessment of viability based on the visual pattern of gastric fluorescence was recorded. If nonviable (lack of defined vessels), a partial gastrectomy was performed and submitted for histopathology. The stapled gastrectomy line was imaged. Viable (defined vessels) and nonviable fluorescence intensities were compared with healthy dogs undergoing surgery for nongastrointestinal disease. RESULTS: Subjective assessment diagnosed 17 viable and three nonviable GDVs (2 fundi; 1 cardia). Near-infrared imaging demonstrated nonviable gastric fluorescence in 4 dogs (3 fundi/cardia; 1 fundus). The surgeon's margins for resection were altered in 3/20 dogs. Fluorescence intensity (cardia, fundus, body, pylorus) was lower in GDV viable (30.59%, p = .04; 38.17%, p < .01; 51.18%, p < .01; 44.12%, p= .01) and nonviable (11.00%, p < .01; 4.33%, p < .01; 57.67%, p = .22; 54.33%, p = .72) dogs compared to healthy controls (44.7%, 70.05%, 84.00%, 63.95%). Fundic fluorescence was less in nonviable gastric tissue in comparison with viable gastric tissue (p = .03). Fluorescence of the gastrectomy staple line approximated that of viable tissue. CONCLUSION: Near-infrared fluorescence can identify histologically confirmed nonviable gastric tissue. CLINICAL SIGNIFICANCE: These results provide enough evidence to support the implementation of NIRF as an adjunct to gross examination of the gastric wall in dogs with GDV.


Assuntos
Doenças do Cão , Volvo Gástrico , Animais , Cães , Doenças do Cão/cirurgia , Doenças do Cão/diagnóstico por imagem , Volvo Gástrico/veterinária , Volvo Gástrico/cirurgia , Volvo Gástrico/diagnóstico por imagem , Feminino , Estudos de Casos e Controles , Masculino , Gastrectomia/veterinária , Gastrectomia/métodos , Estudos Prospectivos , Espectroscopia de Luz Próxima ao Infravermelho/veterinária , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Dilatação Gástrica/veterinária , Dilatação Gástrica/cirurgia , Dilatação Gástrica/diagnóstico por imagem , Imagem Óptica/veterinária , Imagem Óptica/métodos , Estômago/diagnóstico por imagem , Estômago/cirurgia , Fluorescência
4.
J Med Virol ; 94(3): 1175-1185, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34761824

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has particularly affected countries with weakened health services in Latin America, where proper patient management could be a critical step to address the epidemic. In this study, we aimed to characterize and identify which epidemiological, clinical, and paraclinical risk factors defined COVID-19 infection from the first confirmed cases through the first epidemic wave in Venezuela. A retrospective analysis of consecutive suspected cases of COVID-19 admitted to a sentinel hospital was carried out, including 576 patient cases subsequently confirmed for severe acute respiratory syndrome coronavirus 2 infection. Of these, 162 (28.1%) patients met the definition criteria for severe/critical disease, and 414 (71.2%) were classified as mild/moderate disease. The mean age was 47 (SD 16) years, the majority of which were men (59.5%), and the most frequent comorbidity was arterial hypertension (23.3%). The most common symptoms included fever (88.7%), headache (65.6%), and dry cough (63.9%). Severe/critical disease affected mostly older males with low schooling (p < 0.001). Similarly, higher levels of glycemia, urea, aminotransferases, total bilirubin, lactate dehydrogenase, and erythrocyte sedimentation rate were observed in severe/critical disease patients compared to those with mild/moderate disease. Overall mortality was 7.6% (44/576), with 41.7% (28/68) dying in hospital. We identified risk factors related to COVID-19 infection, which could help healthcare providers take appropriate measures and prevent severe clinical outcomes. Our results suggest that the mortality registered by this disease in Venezuela during the first epidemic wave was underestimated. An increase in fatalities is expected to occur in the coming months unless measures that are more effective are implemented to mitigate the epidemic while the vaccination process is ongoing.


Assuntos
COVID-19 , COVID-19/diagnóstico , COVID-19/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Venezuela/epidemiologia
5.
J Am Acad Dermatol ; 87(1): 121-130, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-33887421

RESUMO

BACKGROUND: Immunotherapy is emerging as an alternative treatment for Merkel cell carcinoma, but its long-term effects on response, survival, and safety are not well established. High-quality evidence is needed to estimate the efficacy of this treatment and to review the characteristics of patients and tumors that might improve outcomes. OBJECTIVE: To summarize efficacy and safety of immunotherapy in patients with Merkel cell carcinoma. METHODS: A systematic review was performed for studies published in MEDLINE, Web of Science, Scopus, and EMBASE. Two reviewers examined the literature and data extraction in duplicate. We estimated the proportions for objective responses, progression-free survival, overall survival, and treatment-related adverse events. Associations between objective response rate and immunobiologic markers were analyzed. RESULTS: Six clinical trials of 201 patients treated with immunotherapy were included. The objective response rate was 51% (95% confidence interval, 0.40-0.62; I2 = 37.1%) and grade ≥3 treatment-related adverse events were observed in 18% (95% confidence interval, 0.11-0.29; I2 = 49.5%) of patients. No significant difference was observed between response rates and immunobiologic characteristics. CONCLUSIONS: A significantly reduced tumor diameter with durable response rates and a safe profile are obtained with immunotherapy. Similar response rates achieved on either subgroup of viral status or programmed death ligand 1 expression suggests that it might act on multiple, unexplored pathways.


Assuntos
Carcinoma de Célula de Merkel , Neoplasias Cutâneas , Carcinoma de Célula de Merkel/patologia , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia/efeitos adversos , Intervalo Livre de Progressão , Neoplasias Cutâneas/patologia
6.
J Enzyme Inhib Med Chem ; 37(1): 973-985, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35317680

RESUMO

As regioisomers/bioisosteres of 1a, a 4-phenylbenzamide tranylcypromine (TCP) derivative previously disclosed by us, we report here the synthesis and biological evaluation of some (hetero)arylbenzoylamino TCP derivatives 1b-6, in which the 4-phenyl moiety of 1a was shifted at the benzamide C3 position or replaced by 2- or 3-furyl, 2- or 3-thienyl, or 4-pyridyl group, all at the benzamide C4 or C3 position. In anti-LSD1-CoREST assay, all the meta derivatives were more effective than the para analogues, with the meta thienyl analogs 4b and 5b being the most potent (IC50 values = 0.015 and 0.005 µM) and the most selective over MAO-B (selectivity indexes: 24.4 and 164). When tested in U937 AML and prostate cancer LNCaP cells, selected compounds 1a,b, 2b, 3b, 4b, and 5a,b displayed cell growth arrest mainly in LNCaP cells. Western blot analyses showed increased levels of H3K4me2 and/or H3K9me2 confirming the involvement of LSD1 inhibition in these assays.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Compostos Heterocíclicos/farmacologia , Histona Desmetilases/antagonistas & inibidores , Tranilcipromina/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/química , Histona Desmetilases/metabolismo , Humanos , Estrutura Molecular , Monoaminoxidase/metabolismo , Relação Estrutura-Atividade , Tranilcipromina/síntese química , Tranilcipromina/química , Células Tumorais Cultivadas
7.
Clin Oral Investig ; 26(6): 4327-4335, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35142924

RESUMO

OBJECTIVES: To evaluate and to compare the clinical performance and survival rate of posterior monolithic and veneered zirconia fixed partial dentures (FPDs). MATERIAL AND METHODS: Sixty 3-unit posterior FPDs were included in the study. The patients were randomly distributed into two groups (n = 30 each) to receive either a monolithic (Zenostar T, Wieland Dental) or veneered zirconia (IPS e.max ZirCAD, Ivoclar Vivadent) FPD. Each patient received only 1 FPD. Tooth preparations were scanned (Trios 3, 3Shape), designed (Dental System 2016, 3 Shape), milled (Zenotec CAM 3.2, Wieland Dental), and cemented with a resin cement. Technical and biological outcomes and periodontal parameters were assessed. Data analysis was made using the Friedman and the Wilcoxon signed-rank tests with the Bonferroni correction and the Mann-Whitney U test. RESULTS: The survival rate at 3 years was 100% for veneered and 90% for monolithic zirconia restorations. Three monolithic zirconia FPDs were lost because of biologic complications. The main complication in the veneered zirconia FPDs was the fracture of the veneering ceramic in 4 of the veneered zirconia FPDs. No fracture of the frameworks was observed in any of the groups. All restorations were assessed as satisfactory after 3 years. No differences in periodontal parameters were observed between the groups. CONCLUSIONS: The results of this study suggest that monolithic zirconia and complete digital flow could be a viable alternative to veneered zirconia in the posterior regions. CLINICAL RELEVANCE: The monolithic zirconia restorations with a digital workflow can be a viable alternative in posterior fixed partial dentures, with good periodontal outcomes. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (Identifier NCT 04,879,498).


Assuntos
Porcelana Dentária , Falha de Restauração Dentária , Desenho Assistido por Computador , Facetas Dentárias , Prótese Parcial Fixa , Seguimentos , Humanos , Zircônio
8.
Rev Med Chil ; 150(12): 1674-1680, 2022 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-37906789

RESUMO

BACKGROUND: In 2008, the Chilean National Nursing Examination Commission, COENENF, developed a national nursing exam (ENENF). Since 2013, COENENF has implemented a validated opinion survey at the time of the national examination to strengthen the quality of the exam and facilitate its continuous improvement. AIM: To determine the perception of nursing students about general aspects, specific areas, representativeness, mastery and usefulness of the 2018 ENENF. MATERIAL AND METHODS: A descriptive, cross-sectional study, using a self-administered Likert-type survey, was administered in 2018 to 2949 last-year nursing students from 29 nursing schools who took the ENENF. The survey comprised three areas: representativeness of the questions, student mastery of each area, and the usefulness of the exam. RESULTS: Students had a positive perception of the Chilean ENENF and its application. Theoretical knowledge is effectively assessed and close to half of the sample agreed that the ENENF is useful. The results also suggest areas that should be improved. CONCLUSIONS: Nursing students had a positive perception of the ENENF.


Assuntos
Estudantes de Enfermagem , Humanos , Estudos Transversais , Chile , Inquéritos e Questionários , Percepção
9.
J Prosthodont ; 31(7): 606-613, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34860426

RESUMO

PURPOSE: To compare the load to fracture of cobalt-chromium (Co-Cr) 3-unit posterior fixed partial denture (FPD) frameworks manufactured by conventional and digital techniques and to evaluate the influence of the framework design on the fracture load. MATERIAL AND METHODS: Eighty 3-unit Co-Cr posterior FPD frameworks were fabricated with two designs: intermediate pontic (n = 40) and cantilever (n = 40). Each design was randomly divided into four groups (n = 10): casting, direct metal laser sintering, soft metal milling, and hard metal milling. After thermal cycling, all specimens were subjected to a 3-point bending test until fracture. Data were statistically analyzed using one-way ANOVA, Welch and Brown-Forsythe test, Ryan-Einot-Gabriel-Welsch F and Tamhane T2 post hoc test, Student's t test, and Weibull statistics (α = 0.05). RESULTS: Significant differences (p < 0.001; F = 39.59) were found among intermediate pontic frameworks (except between laser sintering and hard metal milling), and cantilevered frameworks (F = 36.75) (except between laser sintering and hard metal milling, and casting and soft metal milling). The cantilever groups showed load to fracture values significantly lower than those of the intermediate pontic (p < 0.001; F = 28.29). The Weibull statistics corroborated the results. CONCLUSIONS: Hard metal milling and laser sintered frameworks exhibited the highest load to fracture values. However, all tested frameworks demonstrated clinically acceptable load to fracture values. The framework design directly affected the fracture load, with drastically lower values in cantilevered frameworks.


Assuntos
Cromo , Tecnologia Digital , Cobalto , Desenho Assistido por Computador , Prótese Parcial Fixa , Humanos , Teste de Materiais
10.
J Undergrad Neurosci Educ ; 21(1): A47-A51, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-38322048

RESUMO

Technologies such as 3D printing and virtual/augmented reality have great potential for improving the teaching of highly spatial topics such as neuroanatomy. We created a set of 3D printed and virtual brain cross-sections using a high-resolution MRI dataset. These resources have been made freely available via online repositories. We also report a pilot study of the use of both the physical and virtual specimens in the classroom. Students completed a lab exercise where they used either the 3D printed or virtual brain sections to order a set of axial slices from dorsal to ventral. They then labeled the different structures that they found useful in determining the slices' positions. We measured the students' ability to localize 2D brain cross-sections before and after the lab exercise. Overall, we saw pre- to post-test increases in accuracy on a brain cross-sections task compared to a lecture-based neuroanatomy instruction.

11.
Pediatr Dermatol ; 38(1): 327-328, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33222238

RESUMO

Fibroepithelial polyps are common tumors of mesodermal origin. However, only a few case reports of giant fibroepithelial polyps have been published, and they have mainly involved adults. This case report describes a 3-month-old boy with a pedunculated mass in the scrotum. To our knowledge, this is the first report of a giant congenital fibroepithelial polyp on this location.


Assuntos
Pólipos , Neoplasias Cutâneas , Doenças da Língua , Adulto , Humanos , Lactente , Masculino , Pólipos/diagnóstico , Pólipos/cirurgia , Escroto
12.
Australas J Dermatol ; 62(2): e242-e243, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33040329

RESUMO

Mohs micrographic surgery (MMS) is a technique that allows removal of complex or ill-defined skin cancer, combining tissue preservation and complete microscopic margin control. One of the main challenges of Mohs surgery is to illustrate the exact location of the tumour detected by light microscope. Using a dermoscope allows a fast, easy, reproducible way to accurately illustrate the location of a positive tumour on the Mohs map and ultimately transpose it to the surgical defect of the patient in a more precise way.


Assuntos
Dermoscopia , Margens de Excisão , Cirurgia de Mohs/métodos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Humanos
14.
Environ Toxicol ; 35(2): 254-267, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31670470

RESUMO

Global use of azole fungicides is expected to increase over the next several years. Triticonazole is a triazole fungicide that is used for turf protection, residential, and other commercial applications. As such, it can enter local rural and urban water systems via run-off and rain events. Early life stages of aquatic organisms can be susceptible to pesticides that enter the water, but in the case of triticonazole, data on the potential for subacute toxicity are lacking. Here, we determined the effects of triticonazole on development, oxygen consumption rates, and locomotor activity in zebrafish to address this knowledge gap. Wild-type zebrafish (ABTu strain) embryos and larvae were exposed to triticonazole (1-100 µM) in early development for different lengths of time depending on the assay conducted. Triticonazole did not affect survival nor induce significant deformity (pericardial edema, skeletal defects) in zebrafish at doses up to 100 µM. Oxygen consumption rate was measured in embryos after 24 and 48 hour exposure to triticonazole beginning at ∼6 hpf using the XFe flux analyzer. Triticonazole did not affect basal respiration, oligomycin-induced ATP linked respiration, FCCP-induced maximum respiration, proton leak, spare capacity, nor non-mitochondrial respiration at doses up to 100 µM for 24 hours, even for exposure up to 250 µM for 48 hours. To determine whether the fungicide affected larval swimming activity, the visual motor response test was conducted following triticonazole exposure for 6 days. Larval zebrafish exposed to triticonazole showed hypoactivity in the dark following a 100 µM treatment, suggesting that the fungicide can affect the locomotor activity of zebrafish, albeit at relatively high levels. Given the fact that sublethal biological responses were absent at lower environmentally relevant concentrations, we conclude that triticonazole, relative to other triazole fungicides and types of pesticides, exhibits a relatively low risk of toxicity to the early life stages of fish.


Assuntos
Ciclopentanos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Larva/efeitos dos fármacos , Triazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra , Animais , Locomoção/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Peixe-Zebra/crescimento & desenvolvimento
15.
Fish Physiol Biochem ; 46(2): 597-611, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31820206

RESUMO

High-density culture brings with it chronic stress situations that affect fish welfare. In order to evaluate the effect of tryptophan (Trp) levels on the response to stress, Totoaba macdonaldi juveniles were stocked at low (13.5 kg m-3) and high (27.0 kg m-3) densities (32.5 and 56.4 kg m-3, respectively, at the end of the experiment) in 100-L tanks and fed for 63 days with experimental diets containing different Trp levels: control diet CD0.42 (0.42%) and three supplemented diets with 0.99, 1.55 and 2.19% (0.99Trp, 1.55Trp and 2.19Trp, respectively) (three tanks × density × diet). The high-density stocking fed with CD0.42 diets showed significantly increased blood parameters. Trp decreased catalase (CAT) activity in low- and high-density stocking, while the superoxide dismutase (SOD) activity showed no difference. Serotonin (5-hydroxytryptamine, 5-HT) content decreased, and the serotonin turnover ratio (5-HIAA:5-HT) increased in the brains of fish fed with the CD0.42 diet. Indeed, Trp-supplemented diets helped to restore homeostasis in high-density growth conditions as evaluated by the hematological and plasma parameters as well as the serotonergic activity. When the fish were provided a diet containing moderate Trp levels, plasma cortisol increased under high-density conditions. However, no differences were observed among stock densities when totoaba were fed with the 2.19Trp diet. Notably, survival was unaffected by both Trp or densities, but weight gain (WG) decreased with the dietary Trp levels in the high density culture. In sum, Trp supplementation decreased the parameter values linked to stress response on totoaba juveniles cultured at high stock densities.


Assuntos
Suplementos Nutricionais , Homeostase/fisiologia , Perciformes/fisiologia , Triptofano , Ração Animal , Animais , Dieta , Estresse Fisiológico
16.
Environ Monit Assess ; 192(12): 783, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33236254

RESUMO

An industrial accident resulted in a gas oil spill of 11,808 barrels in the upper part of the Coatzacoalcos River watershed. After river shore cleanup, concentrations of total petroleum hydrocarbons (TPH) and polycyclic aromatic hydrocarbons (PAH) in muscle (+ skin) were determined in captured fish to evaluate human health risk due to fish consumption post-spill in the most affected communities. Data on fish consumption, body weight, and diet factor were collected by questionnaires and field observations. Using standard formulas for carcinogenic and non-carcinogenic substances, site-specific remediation levels were calculated in fish, comparing them to the real levels observed. Likewise, the levels of PAHs in fish captured pre- and post-spill were compared to determine their origin (pyrolytic vs. petrogenic). The TPH concentrations were between 119,000 and 523,000 ng/g (dry weight) and no significant difference (P > 0.05) was found pre- vs. post-spill. The concentration of total PAHs varied between 2494.83 and 35,412.23 ng/g (dry weight), with the concentrations of naphthalene (520.9 ng/g) and phenanthrene (7532.7 ng/g) being much higher than in control samples, and being from the gas oil spill (petrogenic origin). The site-specific remediation levels calculated for TPH and PAH were much higher than the maximum levels actually detected. No human health risks were found from hydrocarbons from the spill, at least after cleanup efforts and natural attenuation (six months).


Assuntos
Poluição por Petróleo , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Animais , Monitoramento Ambiental , Humanos , México , Poluição por Petróleo/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Rios , Poluentes Químicos da Água/análise
17.
Plant Physiol ; 178(1): 163-173, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30068539

RESUMO

Agricultural crops are exposed to a range of daylengths, which act as important environmental cues for the control of developmental processes such as flowering. To explore the additional effects of daylength on plant function, we investigated the transcriptome of Arabidopsis (Arabidopsis thaliana) plants grown under short days (SD) and transferred to long days (LD). Compared with that under SD, the LD transcriptome was enriched in genes involved in jasmonic acid-dependent systemic resistance. Many of these genes exhibited impaired expression induction under LD in the phytochrome A (phyA), cryptochrome 1 (cry1), and cry2 triple photoreceptor mutant. Compared with that under SD, LD enhanced plant resistance to the necrotrophic fungus Botrytis cinerea This response was reduced in the phyA cry1 cry2 triple mutant, in the constitutive photomorphogenic1 (cop1) mutant, in the myc2 mutant, and in mutants impaired in DELLA function. Plants grown under SD had an increased nuclear abundance of COP1 and decreased DELLA abundance, the latter of which was dependent on COP1. We conclude that growth under LD enhances plant defense by reducing COP1 activity and enhancing DELLA abundance and MYC2 expression.


Assuntos
Arabidopsis/metabolismo , Ciclopentanos/metabolismo , Luz , Oxilipinas/metabolismo , Fotoperíodo , Arabidopsis/genética , Arabidopsis/microbiologia , Proteínas de Arabidopsis/genética , Botrytis/fisiologia , Criptocromos/genética , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Mutação , Fitocromo A/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Plantas Geneticamente Modificadas , Transcriptoma/efeitos da radiação , Ubiquitina-Proteína Ligases/genética
18.
Bioconjug Chem ; 29(2): 316-323, 2018 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-29188996

RESUMO

Protein prenylation is a post-translational modification that involves the addition of one or two isoprenoid groups to the C-terminus of selected proteins using either farnesyl diphosphate or geranylgeranyl diphosphate. Three crucial enzymatic steps are involved in the processing of prenylated proteins to yield the final mature product. The farnesylated dodecapeptide, a-factor, is particularly useful for studies of protein prenylation because it requires the identical three-step process to generate the same C-terminal farnesylated cysteine methyl ester substructure present in larger farnesylated proteins. Recently, several groups have developed isoprenoid analogs bearing azide and alkyne groups that can be used in metabolic labeling experiments. Those compounds have proven useful for profiling prenylated proteins and also show great promise as tools to study how the levels of prenylated proteins vary in different disease models. Herein, we describe the preparation and use of prenylated a-factor analogs, and precursor peptides, to investigate two key questions. First, a-factor analogues containing modified isoprenoids were prepared to evaluate whether the non-natural lipid group interferes with the biological activity of the a-factor. Second, a-factor-derived precursor peptides were synthesized to evaluate whether they can be efficiently processed by the yeast proteases Rce1 and Ste24 as well as the yeast methyltransferase Ste14 to yield mature a-factor analogues. Taken together, the results reported here indicate that metabolic labeling experiments with azide- and alkyne-functionalized isoprenoids can yield prenylated products that are fully processed and biologically functional. Overall, these observations suggest that the isoprenoids studied here that incorporate bio-orthogonal functionality can be used in metabolic labeling experiments without concern that they will induce undesired physiological changes that may complicate data interpretation.


Assuntos
Alcinos/química , Azidas/química , Fator de Acasalamento/química , Proteínas de Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/química , Terpenos/química , Alcinos/síntese química , Alcinos/metabolismo , Azidas/síntese química , Azidas/metabolismo , Linhagem Celular , Fator de Acasalamento/síntese química , Fator de Acasalamento/metabolismo , Prenilação de Proteína , Proteólise , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/síntese química , Proteínas de Saccharomyces cerevisiae/metabolismo , Terpenos/síntese química , Terpenos/metabolismo
19.
Arch Toxicol ; 92(3): 1037-1048, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29204679

RESUMO

Early life exposure to environmental pollutants and toxic chemicals has been linked to learning and behavioral alterations in children. iAs exposure is associated with different types neurological disorders such as memory and learning impairment. iAs is methylated in the brain by the arsenic III-methyltransferase in a process that requires glutathione (GSH). The xCT-antiporter cell membrane transporter participates in the influx of cystine for GSH synthesis in exchange for glutamate in a 1:1 ratio. In CD-1 mice gestationally exposed to 20 ppm of sodium arsenite in drinking water, we have previously observed up-regulation of xCT in the male mouse hippocampus which caused glutamatergic synapse alterations affecting learning and memory processes. Here, we used the same gestational iAs exposure model to investigate whether the up-regulation of xCT and down-regulation of GLT-1 transporters were associated with higher levels of extracellular glutamate and changes in the expression of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor, responsible for excitatory fast synaptic transmission. The induction of LTP in the perforant-dentate gyrus pathway (PP-DG) of the hippocampus was also studied, as well as learning and memory formation using the water maze test. Changes in GSH levels were also tested in the hippocampus of animals exposed to iAs. Results showed increased GSH synthesis (p < 0.05), associated with significantly higher extracellular glutamate levels in iAs exposed mice. Exposure was also significantly associated with AMPA subunits down-regulation, deficient LTP induction, and lower excitability of the PP-DG pathway. In addition, animals showed deficient learning and memory in the Morris Water Maze test.


Assuntos
Arsênio/toxicidade , Ácido Glutâmico/metabolismo , Hipocampo/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal , Receptores de Glutamato/metabolismo , Animais , Giro Denteado/efeitos dos fármacos , Giro Denteado/metabolismo , Feminino , Glutationa/metabolismo , Hipocampo/metabolismo , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Transtornos da Memória/etiologia , Camundongos Endogâmicos , Via Perfurante/efeitos dos fármacos , Gravidez , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/metabolismo
20.
Am J Dermatopathol ; 39(5): 404-411, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27984232

RESUMO

Balloon cell melanoma (BCM) with metastasis is a rarely occurring neoplasia. The incidence of BCM is low, and hence, the frequency of these lesions presenting metastasis is even less frequent. This review exposes the balloon cell metastasis cases that have been published and a new case. These cases share the histopathological features but the location of initial melanoma, age and sex vary. It is relevant for the dermatologist and dermatopathologist to keep in mind the diagnosis of BCM and consider the possibility of it metastasizing as nonpigmented skin lesions.


Assuntos
Linfonodos/patologia , Melanoma/patologia , Melanoma/terapia , Neoplasias Cutâneas/patologia , Idoso de 80 Anos ou mais , Feminino , Humanos , Invasividade Neoplásica/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Doenças Raras , Medição de Risco , Neoplasias Cutâneas/terapia
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