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1.
Orbit ; : 1-4, 2024 May 26.
Article in English | MEDLINE | ID: mdl-38796753

ABSTRACT

An 88-year-old male patient presented with a large mass on the left lateral bulbar conjunctiva. The tumor appeared two months after the resection of a conjunctival atypical fibroxanthoma (AFX) performed by a cornea specialist. Magnetic resonance imaging of the orbits showed deep orbital invasion along the lateral rectus muscle. The mass and the entire conjunctival sac were totally excised with lid-sparing orbital exenteration. Histopathological analysis confirmed that the mass was an extension of the AFX. Two weeks after surgery, large B-cell lymphoma was diagnosed in the oropharynx. Chemotherapy was initiated, and after seven months of follow-up, there was no recurrence of the AFX. The authors believe that this is the first report of orbital invasion by AFX.

2.
Front Public Health ; 10: 884701, 2022.
Article in English | MEDLINE | ID: mdl-35677763

ABSTRACT

A multi-epitope protein expressed in a prokaryotic system, including epitopes of Env, Gag, and Tax proteins of both HTLV-1 and HTLV-2 was characterized for HTLV-1/2 serological screening. This tool can contribute to support the implementation of public policies to reduce HTLV-1/2 transmission in Brazil, the country with the highest absolute numbers of HTLV-1/2 infected individuals. The chimeric protein was tested in EIA using serum/plasma of HTLV-infected individuals and non-infected ones from four Brazilian states, including the North and Northeast regions (that present high prevalence of HTLV-1/2) and Southeast region (that presents intermediate prevalence rates) depicting different epidemiological context of HTLV-1/2 infection in our country. We enrolled samples from Pará (n = 114), Maranhão (n = 153), Minas Gerais (n = 225) and São Paulo (n = 59) states; they are from blood donors' candidates (Pará and Minas Gerais), pregnant women (Maranhão) and HIV+/high risk for sexually transmitted infection (STI; São Paulo). Among the HTLV-1/2 positive sera, there were co-infections with viral (HTLV-1 + HTLV-2, HIV, HCV, and HBV), bacterial (Treponema pallidum) and parasitic (Trypanosoma cruzi, Schistosma mansoni, Strongyloides stercoralis, Entamoeba coli, E. histolytica, and Endolimax nana) pathogens related to HTLV-1/2 co-morbidities that can contribute to inconclusive diagnostic results. Sera positive for HIV were included among the HTLV-1/2 negative samples. Considering both HTLV-1 and HTLV-2-infected samples from all states and different groups (blood donor candidates, pregnant women, and individuals with high risk for STI), mono or co-infected and HTLV-/HIV+, the test specificity ranged from 90.09 to 95.19% and the sensitivity from 82.41 to 92.36% with high accuracy (ROC AUC = 0.9552). This multi-epitope protein showed great potential to be used in serological screening of HTLV-1 and HTLV-2 in different platforms, even taking into account the great regional variation and different profile of HTLV-1 and HTLV-2 mono or co-infected individuals.


Subject(s)
HIV Infections , HTLV-I Infections , HTLV-II Infections , Human T-lymphotropic virus 1 , Sexually Transmitted Diseases , Brazil/epidemiology , Epitopes , Female , HIV Infections/diagnosis , HTLV-I Infections/diagnosis , HTLV-I Infections/epidemiology , HTLV-II Infections/diagnosis , HTLV-II Infections/epidemiology , Human T-lymphotropic virus 2 , Humans , Pregnancy , Sexually Transmitted Diseases/epidemiology
3.
Astrobiology ; 22(7): 800-811, 2022 07.
Article in English | MEDLINE | ID: mdl-35639110

ABSTRACT

Samples of α-glycine (α-GLY; 230-350 nm) were irradiated in laboratory as a function of electron beam energies (0.25, 0.50, and 1.00 keV) at room temperature (293-295 K). The evolution of α-glycine irradiation process was monitored in real time by infrared spectroscopy (Fourier transform infrared - FTIR), through specific spectral bands: 2610, 2124, 1410, and 1333 cm-1. A phenomenological model is proposed to describe the column density decay when thick organic samples are processed by ionizing beams. The α-glycine radiolysis has exhibited transient and stationary modes in such thickness films. The first stage is mainly described by one exponential decay, whereas the latter foremost decays linearly; compaction processes have been neglected; glycine dissociation and sputtering processes are assumed to be responsible for the damage caused by the electron beam impact through the solid film. The second (stationary) stage is due to equilibrium between a partially shielded bulk radiolysis and sputtering of protective layers. The decay rates are measured for the transient and stationary modes and allow determining the processing velocity of the samples as a function of the electron beam energy. Finally, the model is applied to space weathering to find out the typical sputtering rate of organic compounds on the surface of astrophysical analogs with no protection layers attacked by solar wind (SW) electrons at ≈1 AU. Although the velocity of processing materials in SW has natural competing effects, such as regolith overturn by impacts of micro- and macrometeorites and downslope motion of material that is unstable due to changes in the geopotential of the airless bodies (e.g., asteroid 101955 Bennu), these competing processes are not included in the simulations presented here.


Subject(s)
Electrons , Weather , Glycine , Spectrophotometry, Infrared
4.
Rev. Ciênc. Méd. Biol. (Impr.) ; 21(1): 53-59, maio 05,2022. fig, tab
Article in Portuguese | LILACS | ID: biblio-1370669

ABSTRACT

Introdução: as terapias alternativas que utilizam plantas medicinais e fitoterápicos são bastante comuns no Brasil. Dentre várias espécies vegetais brasileiras utilizadas em terapias destacam-se as espécies da família Malvaceae. Objetivos: o presente estudo teve como objetivo avaliar a citotoxicidade in vitro e a genotoxicidade ex-vivo em compostos da Pavonia glazioviana Gürke espécie brasileira pertencente à família Malvaceae. Metodologia: métodos in vitro foram utilizados para verificar o potencial citotóxico por meio de ensaios hemolíticos e anti-hemolíticos e da análise genotóxica ex-vivo. O Extrato Etanólico Bruto (EEB) e Fração Clorofórmico (FC) foram obtidos na amostra vegetal utilizada neste estudo. Resultados: os produtos EEB-Pg e FC-Pg apresentaram baixo efeito citotóxico apenas nas concentrações de 50 e 100 µg / mL. As amostras expostas às concentrações de 500 e 1000 µg / mL apresentaram índice hemolítico alto a moderado com lise superior a 60%. Foi descrito efeito anti-hemolítico moderado em todas as amostras tratadas com 500 e 1000 µg / mL, com hemólise < 60%. Além disso, os compostos mostraram baixo efeito genotóxico ex-vivo, com um índice geral de células normais superior a 84% em todas as concentrações. Conclusões: os resultados sugerem um baixo perfil tóxico dos compostos obtidos da espécie Pavonia glazioviana, indicando limites seguros para o uso desses produtos naturais.


Introduction: alternative therapies using medicinal plants and herbal medicines are quite common in Brazil. Among several Brazilian plant species used in therapies, the species of the Malvaceae family stand out. Objetctives: the present study aimed to evaluate the in vitro cytotoxicity and ex-vivo genotoxicity in compounds of the Brazilian Pavonia glazioviana Gürke belonging to the Malvaceae family. Methodology: in vitro methods were used to verify the cytotoxic potential through hemolytic and antihemolytic assays and the ex-vivo genotoxic analysis. The Crude Etanolic Extract (CEE) and Cloroformic Fraction (CF) was obtained in vegetal sample used on this study. Results: the CEE-Pg and CF-Pg products only showed a low cytotoxic effect at the concentrations of 50 and 100 µg/mL. The exposure to the concentrations of 500 and 1000 µg/mL showed a high to moderate hemolytic index with lysis higher than 60%. A moderate anti-hemolytic effect was described in all samples treated with 500 and 1000 µg/mL, with hemolysis <60%. In addition, the compounds showed low ex-vivo genotoxic effect with a general index of normal cells greater than 84% at all concentrations. Conclusion: the results suggest a low toxic profile of the compounds obtained from the Pavonia glazioviana Gürke species belonging to the Malvaceae family, indicating safe limits for the use of these natural products.


Subject(s)
Humans , Plant Extracts/pharmacology , Malvaceae/chemistry , Genotoxicity , Hemolytic Agents/pharmacology , Plants, Medicinal/chemistry , Dose-Response Relationship, Drug
5.
Med Oral Patol Oral Cir Bucal ; 27(1): e35-e41, 2022 Jan 01.
Article in English | MEDLINE | ID: mdl-34564682

ABSTRACT

BACKGROUND: Angina bullosa haemorrhagica (ABH) is characterized by the recurrent appearance of blood blisters on the oral mucosa, mainly in adults' soft palate. In general, the blisters rupture spontaneously, lacking the necessity for biopsy. We report the clinical features of 23 ABH cases, emphasizing the clinical behavior and the management of these conditions. MATERIAL AND METHODS: A retrospective descriptive cross-sectional study was performed. A total of 12,727 clinical records of oral and maxillofacial lesions from four dental services in Brazil were analyzed. Clinical data were collected from the clinical records and evaluated. RESULTS: The series comprised 12 males (52.2%) and 11 females (47.8%), with a mean age of 56.8 ± 14.6 years (ranging: 24-82 years) and a 1.1:1 male-to-female ratio. Most of the lesions affected the soft palate (n = 15, 65.2%). Clinically, the lesions presented mainly as an asymptomatic (n = 17, 73.9%) blood-filled blister that ruptured after a few minutes or hours, leaving an erosion. The masticatory trauma was the most frequent triggering event. No patient had coagulation disorders. A biopsy was performed in only four cases (17.4%). Treatment was symptomatic with a favorable outcome. CONCLUSIONS: ABH is still poorly documented in the literature, and its etiology remains uncertain. ABH mainly affects the soft palate of elderly adults and has a favorable evolution in a few days. The therapeutic approach is often focused only on the relief of symptoms. However, it can share some clinical features with more serious diseases. Therefore, clinicians must recognize these lesions to avoid misdiagnosis.


Subject(s)
Mouth Diseases , Oral Hemorrhage , Adult , Aged , Blister , Brazil , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Retrospective Studies
6.
J Dairy Sci ; 105(2): 1170-1185, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34799111

ABSTRACT

The objective of this experiment was to examine the effect of milk replacer (MR) feeding rate (FR) and frequency (FF) on glucose metabolism before and after weaning during summer and winter in the subtropical climate of the southeastern United States. Holstein calves (n = 48/season) were enrolled at 8 d of age (DOA) in the summer (June to August, body weight = 40.6 ± 0.7 kg) and winter (November to January, body weight = 41.9 ± 0.8 kg). In each season, calves were randomly assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement including 2 FR [0.65 (low) or 0.76 kg of solids/d (high) of a 26% CP and 17% fat MR] and 2 FF [2× (0700 and 1600 h) or 3× (0700, 1600, and 2200 h)]. Calves were managed similarly and housed in polyethylene hutches bedded with sand. Milk replacer (12.5%) was fed based on treatments until 42 DOA when FR was reduced by half and offered 1×/d (0700 h) for 7 d. Plasma was collected weekly at 1400 h for analyses of glucose and insulin concentrations in all calves. Pre- and postprandial glucose and insulin concentrations of a subset of calves (n = 10/treatment per season) were measured on 20 DOA. A subset of calves (n = 8/treatment per season) was subjected to an intravenous glucose tolerance test (GTT) on 27 and 57 DOA and insulin challenge on 28 and 58 DOA at 1030 h. Average ambient temperature was 26.1 ± 2.2°C in summer and 12.9 ± 5.4°C in winter. During the preweaning period in both seasons, feeding high increased plasma glucose concentrations compared with low, and increasing FF reduced basal insulin concentrations. Compared with 2×, feeding 3× did not affect postprandial glucose but lowered insulin in the summer, whereas in the winter, increased glucose from 30 to 180 min but lowered insulin from 240 to 420 min after MR feeding. Following GTT before weaning in both seasons, 3× reduced insulin increment and area under the curve compared with 2× without affecting glucose disposal. After weaning, treatment did not affect glucose disposal or insulin responses after GTT during winter, but calves fed 3× had faster glucose disposal and stronger insulin responses than 2× during summer. In both summer and winter, preweaned calves fed 3× had greater decrement and area under the curve of plasma glucose after insulin challenge, suggesting enhanced peripheral tissue insulin response compared with 2×. This effect persisted after weaning only during summer. Increasing FR had no effect on metabolic responses in both seasons. In conclusion, increasing MR FF from 2 to 3 times per day reduced insulin secretion but enhanced insulin response on peripheral tissues of preweaned calves regardless of season.


Subject(s)
Milk Substitutes , Milk , Animal Feed/analysis , Animals , Body Weight , Cattle , Diet/veterinary , Glucose , Weaning
7.
J Dairy Sci ; 105(2): 1150-1169, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34799113

ABSTRACT

To evaluate the effects of milk replacer (MR) feeding rate (FR) and frequency (FF) on performance, abomasal emptying, and nutrient digestibility in the southeastern United States, Holstein calves (n = 48/season) were enrolled at 8 d of age (DOA) during summer [June to August, body weight (BW; mean ± SD) = 40.71 ± 4.35 kg] and winter (November to January, BW = 42.03 ± 3.83 kg). Within season, calves were randomly assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement including 2 FR [0.65 (low) or 0.76 kg of solid per day (high) of a 26% crude protein and 17% fat MR], and 2 FF [2× (0700 and 1600 h) or 3× (0700, 1600, and 2200 h) daily]. Calves were housed in polyethylene hutches and managed similarly throughout the trial. Milk replacer (12.5% solids) was fed to calves based on their respective treatments until 42 DOA, when MR allowance was reduced by 50% and offered once a day (0700 h) for the following 7 d until weaning. Calves remained on trial until 63 DOA. Calf starter and water were offered ad libitum. Ambient temperature and relative humidity inside and outside hutches were measured hourly. Starter and MR intakes were recorded daily. Respiration rate and rectal temperature were recorded 3 times a week. Structural growth and BW were measured weekly. Acetaminophen (50 mg/kg of BW) mixed with MR was fed to a subset of calves (0700 h, n = 10/treatment per season) on 20 DOA. Plasma was collected at 15, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330, 360, 420, and 480 min after feeding, to analyze acetaminophen. The acetaminophen concentration-time curve was modeled to the first derivative of Siegel's modified power exponential equation, and the time for plasma acetaminophen to reach maximum (Tmax) was calculated to evaluate abomasal emptying rate. During the pre- (14.9-17.9 DOA) and postweaning (51.0-54.0 DOA) periods, a subset (n = 8/treatment per season) of calves was used to determine the apparent digestibility of nutrients, using chromic oxide as the external marker. Feeding 3× reduced preweaning respiration rate during summer and reduced rectal temperature during winter. Increasing FR improved BW gain and structural growth. Feeding more times per day tended to improve growth during winter but not summer. We found no effect of treatment on nutrient digestibility. Increasing FR had no effect on Tmax during winter but tended to delay Tmax of plasma acetaminophen during summer. Regardless of season, increasing FF lowered Tmax of plasma acetaminophen. In conclusion, increasing FF accelerated abomasal emptying and might reduce heat load of preweaning dairy calves but improved growth only during winter. Increased MR allowance improved growth in both seasons but delayed abomasal emptying only under heat stress conditions.


Subject(s)
Milk Substitutes , Milk , Animal Feed/analysis , Animals , Body Weight , Cattle , Diet/veterinary , Nutrients , Weaning
8.
Viruses ; 13(8)2021 08 05.
Article in English | MEDLINE | ID: mdl-34452409

ABSTRACT

Herpes simplex virus type 1 nucleocapsids are released from the host nucleus by a budding process through the nuclear envelope called nuclear egress. Two viral proteins, the integral membrane proteins pUL34 and pUL31, form the nuclear egress complex at the inner nuclear membrane, which is critical for this process. The nuclear import of both proteins ensues separately from each other: pUL31 is actively imported through the central pore channel, while pUL34 is transported along the peripheral pore membrane. With this study, we identified a functional bipartite NLS between residues 178 and 194 of pUL34. pUL34 lacking its NLS is mislocalized to the TGN but retargeted to the ER upon insertion of the authentic NLS or a mimic NLS, independent of the insertion site. If co-expressed with pUL31, either of the pUL34-NLS variants is efficiently, although not completely, targeted to the nuclear rim where co-localization with pUL31 and membrane budding seem to occur, comparable to the wild-type. The viral mutant HSV1(17+)Lox-UL34-NLS mt is modestly attenuated but viable and associated with localization of pUL34-NLS mt to both the nuclear periphery and cytoplasm. We propose that targeting of pUL34 to the INM is facilitated by, but not dependent on, the presence of an NLS, thereby supporting NEC formation and viral replication.


Subject(s)
Cell Nucleus/metabolism , Herpesvirus 1, Human/metabolism , Viral Proteins/chemistry , Viral Proteins/metabolism , Virus Release , Active Transport, Cell Nucleus , Amino Acid Motifs , Animals , Cell Line , Chlorocebus aethiops , HeLa Cells , Herpesvirus 1, Human/genetics , Humans , Mutation , Vero Cells , Viral Proteins/genetics , Virus Replication
9.
Arch Toxicol ; 95(1): 207-228, 2021 01.
Article in English | MEDLINE | ID: mdl-33078273

ABSTRACT

Due to regulatory bans and voluntary substitutions, halogenated polybrominated diphenyl ether (PBDE) flame retardants (FR) are increasingly substituted by mainly organophosphorus FR (OPFR). Leveraging a 3D rat primary neural organotypic in vitro model (rat brainsphere), we compare developmental neurotoxic effects of BDE-47-the most abundant PBDE congener-with four OPFR (isopropylated phenyl phosphate-IPP, triphenyl phosphate-TPHP, isodecyl diphenyl phosphate-IDDP, and tricresyl phosphate (also known as trimethyl phenyl phosphate)-TMPP). Employing mass spectroscopy-based metabolomics and transcriptomics, we observe at similar human-relevant non-cytotoxic concentrations (0.1-5 µM) stronger developmental neurotoxic effects by OPFR. This includes toxicity to neurons in the low µM range; all FR decrease the neurotransmitters glutamate and GABA (except BDE-47 and TPHP). Furthermore, n-acetyl aspartate (NAA), considered a neurologic diagnostic molecule, was decreased by all OPFR. At similar concentrations, the FR currently in use decreased plasma membrane dopamine active transporter expression, while BDE-47 did not. Several findings suggest astrogliosis induced by the OPFR, but not BDE-47. At the 5 µM concentrations, the OPFR more than BDE-47 interfered with myelination. An increase of cytokine gene and receptor expressions suggests that exposure to OPFR may induce an inflammatory response. Pathway/category overrepresentation shows disruption in 1) transmission of action potentials, cell-cell signaling, synaptic transmission, receptor signaling, (2) immune response, inflammation, defense response, (3) cell cycle and (4) lipids metabolism and transportation. Taken together, this appears to be a case of regretful substitution with substances not less developmentally neurotoxic in a primary rat 3D model.


Subject(s)
Brain/drug effects , Flame Retardants/toxicity , Neurons/drug effects , Neurotoxicity Syndromes/etiology , Organophosphates/toxicity , Animals , Brain/embryology , Brain/metabolism , Cells, Cultured , Female , Gene Expression Profiling , Gestational Age , Halogenated Diphenyl Ethers/toxicity , Metabolome/drug effects , Metabolomics , Neurons/metabolism , Neurons/pathology , Neurotoxicity Syndromes/metabolism , Neurotoxicity Syndromes/pathology , Pregnancy , Rats, Sprague-Dawley , Spheroids, Cellular , Transcriptome/drug effects , Tritolyl Phosphates/toxicity
10.
São José dos Campos; s.n; 2021. 75 p. il., graf., tab..
Thesis in Portuguese | BBO - Dentistry | ID: biblio-1252601

ABSTRACT

O cimento de aluminato de cálcio (CAC) tem se tornado um biomaterial de destaque para a neoformação óssea devido às suas propriedades físicas, mecânicas e biocompatibilidade, além de possuir coeficiente de expansão térmica similar ao osso humano. O objetivo neste trabalho foi avaliar o potencial de regeneração óssea de scaffolds à base de CAC, incorporados ou não com células mesenquimais (MSC) em defeitos ósseos realizados em fêmures de ratos. Foram produzidos 48 scaffolds de CAC e suas blendas fosfato tricálcico (FOSF), óxido de zinco (ZNO) e zircônia (ZIRC), sendo que metade destes foram incorporados com MSC. Vinte e três ratos Wistar foram utilizados, sendo 03 para isolamento das MSC e 20 para confecção de defeitos ósseos em ambos os fêmures. Estes, receberam scaffolds do mesmo material incorporados com MSC do lado esquerdo e não incorporados do lado direito (n=5); e foram eutanasiados 21 dias após o procedimento cirúrgico.Na análise dos scaffolds por microscopia eletrônica de varredura foram verificadas estruturas com poros abertos e interconectados, além de adesão celular em todos os grupos.Na análise histológica, foi observado que todos os grupos apresentaram trabéculas ósseas neoformadas, entremeadas por células da medula óssea e tecido conjuntivo. Na histomorfometria, para os scaffolds não incorporados com MSC, observou-se que o grupo ZIRC apresentou maior neoformação óssea e nos scaffolds incorporados com MSC, o grupo FOSF demonstrou melhores resultados, ambos exibindo diferença estatística para os demais grupos (p<0,05). Na análise intragrupos, todos os grupos exibiram maior neoformação óssea quando incorporados com MSC, exceto o grupo ZIRC, único que apresentou melhores resultados quando não incorporado com MSC. Concluiu-se que scaffolds da blenda ZIRC promovem maior neoformação óssea, porém, quando estes são incorporados com MSC, a blenda FOSF exibe os melhores resultados. A incorporação de MSC influenciou positivamente a neoformação óssea, exceto na blenda ZIRC. Concluiu-se ainda que, dentre todos os grupos, o ZIRC sem células e o FOSF com células mostraram-se mais promissores na neoformação óssea, sem diferença estatística entre eles (p<0,05)(AU)


Calcium aluminate cement (CAC) has become a prominent biomaterial for bone neoformation due to its physical, mechanical and biocompatibility properties, in addition to having a coefficient of thermal expansion similar to human bone. The objective of this work was to evaluate the bone regeneration potential of scaffolds based on CAC, incorporated or not with mesenchymal cells (MSC) in bone defects performed in rat femurs. 48 CAC scaffolds and their tricalcium phosphate (FOSF), zinc oxide (ZNO) and zirconia (ZIRC) blends were produced, half of which were incorporated with MSC.Twenty three Wistar rats were used, being 03 for isolation of MSC and 20 for making bone defects in both femurs. These received scaffolds of the same material incorporated with MSC on the left side and not incorporated on the right side (n = 5); and were euthanized 21 days after the surgical procedure. In the analysis of the scaffolds by scanning electron microscopy, structures with open and interconnected pores were verified, in addition to cell adhesion in all groups. In the histological analysis, it was observed that all groups presented bone trabeculae. neoformed, interspersed with bone marrow cells and connective tissue. In histomorphometry, for the scaffolds not incorporated with MSC, it was observed that the ZIRC group showed greater bone neoformation and in the scaffolds incorporated with MSC, the FOSF group demonstrated better results, both showing statistical difference for the other groups (p <0.05). In the intragroup analysis, all groups exhibited greater bone neoformation when incorporated with MSC, except for the ZIRC group, the only one that showed better results when not incorporated with MSC. It was concluded that scaffolds from the ZIRC blend promote greater bone neoformation, however, when these are incorporated with MSC, the FOSF blend exhibits the best results. The incorporation of MSC positively influenced bone neoformation, except in the ZIRC blend. It was also concluded that, among all groups, ZIRC without cells and FOSF with cells were more promising in bone neoformation, with no statistical difference between them (p <0.05)(AU)


Subject(s)
Bone Regeneration/physiology , Biocompatible Materials/administration & dosage , Mesenchymal Stem Cells/pathology
11.
Front Cell Neurosci ; 14: 25, 2020.
Article in English | MEDLINE | ID: mdl-32153365

ABSTRACT

Selective serotonin reuptake inhibitors (SSRIs) are frequently used to treat depression during pregnancy. Various concerns have been raised about the possible effects of these drugs on fetal development. Current developmental neurotoxicity (DNT) testing conducted in rodents is expensive, time-consuming, and does not necessarily represent human pathophysiology. A human, in vitro testing battery to cover key events of brain development, could potentially overcome these challenges. In this study, we assess the DNT of paroxetine-a widely used SSRI which has shown contradictory evidence regarding effects on human brain development using a versatile, organotypic human induced pluripotent stem cell (iPSC)-derived brain model (BrainSpheres). At therapeutic blood concentrations, which lie between 20 and 60 ng/ml, Paroxetine led to an 80% decrease in the expression of synaptic markers, a 60% decrease in neurite outgrowth and a 40-75% decrease in the overall oligodendrocyte cell population, compared to controls. These results were consistently shown in two different iPSC lines and indicate that relevant therapeutic concentrations of Paroxetine induce brain cell development abnormalities which could lead to adverse effects.

12.
Mater Sci Eng C Mater Biol Appl ; 103: 109742, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31349429

ABSTRACT

This study aimed to develop nanocapsules containing ketoprofen using rose hip oil (Keto-NC) as oil core, and to evaluate their anti-inflammatory activity in acute and chronic ear edema models in mice. Physicochemical characterization, drug release, photostability and cytotoxicity assays were performed for the developed Keto-NC formulations and compared to ketoprofen-loaded nanocapsules using medium chain triglycerides as oil core (Keto-MCT-NC). Anti-inflammatory activity of orally delivered KP (Ketoprofen-free; 10 mg.kg-1) or Keto-NC (2.5; 5; 10 mg.kg-1) was assessed in mouse acute and chronic ear edema induced by croton oil (CO). Edema histological characteristics were determined by H&E stain, and redox parameters were analyzed in blood plasma and erythrocytes. Keto-MCT-NC and Keto-NC did not exhibit differences regarding physicochemical parameters, including size diameters, polydispersity index, pH, Ketoprofen content, and encapsulation efficiency. However, Keto-NC, which contains rose hip oil as lipid core, decreased drug photodegradation under UVC radiation when compared to Keto-MCT-NC. KP or Keto-NC were not cytotoxic to keratinocyte cultures and produced equal edema inhibition in the acute protocol. Conversely, in the chronic protocol, Keto-NC was more effective in reducing edema (~60-70% on 7-9th days of treatment) when compared to KP (~40% on 8-9th days of treatment). This result was confirmed by histological analysis, which indicated reduction of edema and inflammatory infiltrate. A sub-therapeutic dose of Keto-NC (5 mg.kg-1) significantly reduced edema when compared to control. Finally, KP and Keto-NC exhibited similar effects on redox parameters, suggesting that the advantages associated with Ketoprofen nanoencapsulation did not involve oxidative stress pathways. The results showed that Keto-NC was more efficient than KP in reducing chronic inflammation. These data may be important for the development of strategies aiming treatment of chronic inflammatory diseases with fewer adverse effects.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Inflammation/drug therapy , Ketoprofen/pharmacology , Nanocapsules/chemistry , Plant Oils/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Cell Line , Chronic Disease , Disease Models, Animal , Drug Liberation , Drug Stability , Edema/drug therapy , Humans , Keratinocytes/drug effects , Ketoprofen/administration & dosage , Ketoprofen/pharmacokinetics , Male , Mice, Inbred C57BL , Nanocapsules/therapeutic use , Oxidative Stress/drug effects , Rosa/chemistry
13.
Astrobiology ; 19(9): 1123-1138, 2019 09.
Article in English | MEDLINE | ID: mdl-31084501

ABSTRACT

Glycine is an amino acid that has already been detected in space. It is relevant to estimate its resistance under cosmic radiation. In this way, a sublimate of glycine in α-form on KBr substrate was exposed in the laboratory to a 1.0 keV electron beam. The radiolysis study was performed at 40 K, 80 K, and 300 K sample temperatures. These temperatures were chosen to cover characteristics of the outer space environment. The evolution of glycine compaction and degradation was monitored in real time by infrared spectroscopy (Fourier-transform infrared) by investigation in the spectral ranges of 3500-2100, 1650-1200, and 950-750 cm-1. The compaction cross-section increases as the glycine temperature decreases. The glycine film thickness layer of ∼160 nm was depleted completely after ∼15 min at 300 K under irradiation with ∼1.4 µA beam current on the target, whereas the glycine depletion at 40 K and 80 K occurred after about 4 h under similar conditions. The destruction cross-section at room temperature is found to be (13.8 ± 0.2) × 10-17 cm2, that is, about 20 times higher than the values for glycine depletion at lower temperatures (<80 K). Emerging and vanishing peak absorbance related to OCN- and CO bands was observed in 2230-2100 cm-1 during the radiolysis at 40 K and 80 K. The same new IR bands appear in the range of 1600-1500, 1480-1370, and 1350-1200 cm-1 after total glycine depletion for all temperature configurations. A strong N-H deformation band growing at 1510 cm-1 was observed only at 300 K. Finally, the destruction cross-section associated to tholin decay at room temperature is estimated to be (1.30 ± 0.05) × 10-17 cm2. In addition, a correlation between the formation cross-sections for daughter and granddaughter molecules at 300 K is also obtained from the experimental data.


Subject(s)
Electrons , Glycine/radiation effects , Temperature , Crystallography, X-Ray , Glycine/chemistry , Spectroscopy, Fourier Transform Infrared , Time Factors
14.
Adv Physiol Educ ; 42(4): 661-667, 2018 Dec 01.
Article in English | MEDLINE | ID: mdl-30387701

ABSTRACT

A group of teachers from Northeast Brazil developed a model of membrane potentials and action potential and tested the hypothesis that using the peer-instruction model would provide a better performance for students in reading traditional texts and lectures. The results were obtained from 357 students from 20 different courses in 9 different undergraduate programs. All students attended two 100-min theoretical lecture and, at the end of the second lecture, were asked to answer a multiple-choice question (a pretest). In the following lecture, students were divided into three groups: control, text, and model. At the end of the lecture, everyone responded to a posttest. Student performance in the pretest did not differ significantly between groups. In the comparison between the pretest and the posttest, students in the model and text groups significantly improved their performance, but there was no improvement in the control group. In the posttest, the model group presented a better performance than the control group. In the evaluation of the strategies used, 46% of the students indicated that the text would be very useful to remind them about the subject in the future, whereas 80% of those who used the model indicated that it would be very useful or extremely useful. useful. Although it was not possible to support the hypothesis conclusively, the performance model group, at least in part, was due to the use of active methodologies that constitute a differential in the teaching-learning process.


Subject(s)
Action Potentials/physiology , Health Occupations/education , Membrane Potentials/physiology , Models, Biological , Peer Group , Teaching , Educational Measurement/methods , Female , Humans , Male , Students, Health Occupations , Young Adult
15.
Med Oral Patol Oral Cir Bucal ; 23(4): e401-e405, 2018 Jul 01.
Article in English | MEDLINE | ID: mdl-29924755

ABSTRACT

BACKGROUND: Oral focal mucinosis (OFM) is a rare soft tissue lesion of unknown etiology that exhibits tumor-like growth. It is considered the oral counterpart of cutaneous focal mucinosis or cutaneous myxoid cyst. This is a retrospective study of oral OFM diagnosed over a period of 42 years at an oral pathology service. MATERIAL AND METHODS: Clinical, histopathological and immunohistochemical data were analyzed. Alcian blue staining and S-100 immunohistochemistry were performed. RESULTS: Eleven cases were retrieved (4:1 female-to-male ratio). The mean age was 44 years. The gingiva was the most affected site. The main clinical presentation was sessile or pedunculated lesions of fibrous or hyperplasic appearance, most of them asymptomatic. Positive Alcian blue staining and absence of S-100 protein were observed in all specimens, which supported the histological diagnosis of OFM. Surgical excision was the treatment of choice. CONCLUSIONS: Although rare, this study supports the inclusion of OFM in the differential diagnosis of intraoral myxoid lesions.


Subject(s)
Mouth Diseases/pathology , Mucinoses/pathology , Adult , Aged , Diagnosis, Oral , Female , Humans , Male , Middle Aged , Retrospective Studies
16.
Med Oral Patol Oral Cir Bucal ; 23(1): e49-53, 2018 Jan 01.
Article in English | MEDLINE | ID: mdl-29274165

ABSTRACT

BACKGROUND: the objective of this study was to describe the frequency of cystic lesions in a Brazilian population of patients histopathologically diagnosed in the first and second decade of life. MATERIAL AND METHODS: Retrospective descriptive cross-sectional study was performed. Biopsy records were obtained from the archives of a Brazilian referral center between 1980 and 2016. RESULTS: A total of 2.114 biopsy records of pediatric patients were analyzed with oral and maxillofacial lesions. Data such as gender, age, anatomical location, and histopathological diagnosis were collected and categorized. Among all oral and maxillofacial lesions (n=2.114), were diagnosed 294 cases of odontogenic cysts (13.9%) and 16 cases of non-odontogenic cysts (0.8%). The most frequent lesions in each group were, respectively: radicular cyst (n=145) and epidermoid cyst (n=4). These lesions were most common in female (n=158), with a mean age of 14 years. For intraosseous lesions, the mandible (n=148) was the most affected anatomic site; moreover, the floor of the mouth (n=6) was most affected by cysts in soft tissues. CONCLUSIONS: Odontogenic cysts were relatively common in population studied, but non-odontogenic cysts were rare in these patients.


Subject(s)
Nonodontogenic Cysts/epidemiology , Odontogenic Cysts/epidemiology , Adolescent , Brazil/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Epidemiologic Studies , Female , Humans , Infant , Male , Retrospective Studies , Young Adult
17.
Int J Mol Sci ; 18(12)2017 Dec 09.
Article in English | MEDLINE | ID: mdl-29232831

ABSTRACT

The constituents of essential oils are widely found in foods and aromatic plants giving characteristic odor and flavor. However, pharmacological studies evidence its therapeutic potential for the treatment of several diseases and promising use as compounds with analgesic-like action. Considering that pain affects a significant part of the world population and the need for the development of new analgesics, this review reports on the current studies of essential oils' chemical constituents with analgesic-like activity, including a description of their mechanisms of action and chemical aspects.


Subject(s)
Analgesics/therapeutic use , Oils, Volatile/therapeutic use , Pain/drug therapy , Analgesics/chemistry , Animals , Burseraceae/chemistry , Food , Humans , Lamiaceae/chemistry , Molecular Structure , Oils, Volatile/chemistry
18.
Int J Mol Sci ; 18(9)2017 Sep 14.
Article in English | MEDLINE | ID: mdl-28906435

ABSTRACT

Hexavalent chromium (Cr(VI)) is a ubiquitous environmental pollutant, which poses a threat to human public health. Recent studies have shown that mitochondrial biogenesis can be activated by inflammatory and oxidative stress. However, whether mitochondrial biogenesis is involved in Cr(VI)-induced hepatotoxicity is unclear. Here, we demonstrated the induction of inflammatory response and oxidative stress, as indicated by upregulation of inflammatory factors and reactive oxygen species (ROS). Subsequently, we demonstrated that mitochondrial biogenesis, comprising the mitochondrial DNA copy number and mitochondrial mass, was significantly increased in HepG2 cells exposed to low concentrations of Cr(VI). Expression of genes related to mitochondrial function complex I and complex V was upregulated at low concentrations of Cr(VI). mRNA levels of antioxidant enzymes, including superoxide dismutase 1 and 2 (SOD1 and SOD2, respectively), kech like ECH associate protein 1 (KEAP1) and nuclear respiratory factor 2 (NRF-2), were also upregulated. Consistent with the above results, mRNA and protein levels of key transcriptional regulators of mitochondrial biogenesis such as the peroxisome-proliferator-activated receptor γ coactivator-1α (PGC-1α), NRF-1 and mitochondrial transcription factor A (TFAM) were increased by low concentrations of Cr(VI) in HepG2 cells. Moreover, we found that PGC-1α and NRF-1 tended to translocate into the nucleus. The expression of genes potentially involved in mitochondrial biogenesis pathways, including mRNA level of silent information regulator-1 (SIRT1), forkhead box class-O (FOXO1), threonine kinase 1 (AKT1), and cAMP response element-binding protein (CREB1), was also upregulated. In contrast, mitochondrial biogenesis was inhibited and the expression of its regulatory factors and antioxidants was downregulated at high and cytotoxic concentrations of Cr(VI) in HepG2 cells. It is believed that pretreatment with α-tocopherol could be acting against the mitochondrial biogenesis imbalance induced by Cr(VI). In conclusion, our study suggests that the homeostasis of mitochondrial biogenesis may be an important cellular compensatory mechanism against Cr(VI)-induced toxicity and a promising detoxification target.


Subject(s)
Chromium/pharmacology , Hepatocytes/drug effects , Hepatocytes/metabolism , Mitochondria, Liver/drug effects , Mitochondria, Liver/metabolism , Organelle Biogenesis , Cell Death/drug effects , Cytokines/genetics , Cytokines/metabolism , Gene Expression Regulation/drug effects , Hep G2 Cells , Humans , Inflammation Mediators/metabolism , Oxidation-Reduction , Oxidative Stress/drug effects , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reactive Oxygen Species/metabolism , alpha-Tocopherol/pharmacology
19.
J Viral Hepat ; 24(12): 1089-1097, 2017 12.
Article in English | MEDLINE | ID: mdl-28581644

ABSTRACT

Community-based real-world outcomes on effectiveness of antiviral therapies for chronic hepatitis B virus (CHB) in Asians are limited. Whether hepatitis B surface antigen (HBsAg) loss correlates with undetectable virus and alanine aminotransferase (ALT) normalization on treatment or what predicts risk of seroreversion or detectable virus after stopping therapy is unclear. We aim to evaluate rates and predictors of HBsAg loss, seroconversion, ALT normalization and undetectable HBV DNA, including HBsAg seroreversion or re-emergence of HBV DNA among Asian CHB patients. We retrospectively evaluated 1072 CHB adults on antiviral therapy at two community gastroenterology clinics from 1997 to 2015. Rates of HBsAg loss, ALT normalization, achieving undetectable HBV DNA and developing surface antibody (anti-HBs) were stratified by HBeAg status. Following HBsAg loss, HBsAg seroreversion or re-emergence of detectable HBV DNA was analysed. With median treatment of 76.7 months, the overall rate of HBsAg loss was 4.58%, with similar HBsAg loss rates between HBeAg-positive and HBeAg-negative patients (4.44% vs 4.71%, P=.85) in a predominantly Asian population (98.1%). Among HBsAg loss patients, 33.3% developed anti-HBs, 95.8% achieved undetectable virus and 66.0% normalized ALT. No significant baseline or on-treatment predictors of HBsAg loss were observed. While six patients who achieved HBsAg loss had seroreversion with re-emergence of HBsAg positivity, viral load remained undetectable, demonstrating the sustainability of viral suppression. Among a large community-based real-world cohort of Asian CHB patients treated with antiviral therapy, rate of HBsAg loss was 4.58%. Despite only 33.3% of HBsAg loss patients achieving anti-HBs, nearly all patients achieved sustained undetectable virus.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B Surface Antigens/blood , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/virology , Sustained Virologic Response , Adolescent , Adult , Aged , Aged, 80 and over , Alanine Transaminase/blood , Asia , DNA, Viral/blood , Female , Hepatitis B Antibodies , Hepatitis B, Chronic/pathology , Humans , Male , Middle Aged , Retrospective Studies , Seroconversion , Treatment Outcome , Viral Load , Young Adult
20.
Rev. bras. farmacogn ; 27(3): 361-368, May-June 2017. tab, graf
Article in English | LILACS | ID: biblio-898671

ABSTRACT

Abstract Drugs used in the treatment of depression can cross the placenta giving rise to questions regarding the effects these drugs exert on the fetus. Hypericum perforatum L., Hypericaceae, is a natural product used to treat depression. However, information about its toxicity and the occurrence of alterations in the central nervous system development of the offspring is scarce. This work assessed the behavior of adult male rats born from mothers treated with Hypericum extract during gestation and analyzed the fluorescence of the extract in different organs of mothers and fetuses. Male pups were divided into three treated groups, corresponding to the administration of the Hypericum extract to mothers at the dose levels of 36 mg/kg, 72 mg/kg and 144 mg/kg, and one control group in which the mothers received distilled water. At 90 days of age, the offspring underwent the following tests: rotarod, pentobarbital-induced sleep time, elevated plus maze, hole-board and forced swimming test. The observed fluorescence indicated the presence of the extract in all tissues analyzed. The obtained results suggest lasting changes in the performances displayed in the CNS, depression and anxiety tests, indicating that the use of Hypericum during gestation could interfere with the behavioral development of the offspring reducing anxiety and depression when they become adults. We suggest that these alterations are associated with the reprogramming of the brain regions related to changes in emotional reactivity.

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