Cobalt Chloride as a Hypoxia Mimicking Agent Induced HIF-1α and mTOR Expressions of Human Umbilical Cord Mesenchymal Stem Cells

ABSTRACT Objective: To assess the effects of cobalt chloride (CoCl2) as a hypoxia mimicking agent on human umbilical cord mesenchymal stem cells (hUCMSCs) expression of HIF-1α and mTOR for use in regenerative dentistry. Material and Methods: Human umbilical cord mesenchymal stem cells were isolated and then cultured. The characteristics of stemness were screened and confirmed by flow cytometry. The experiment was conducted on hypoxia (H) and normoxia (N) groups. Each group was divided and incubated into 24-, 48-, and 72-hours observations. Hypoxic treatment was performed using 100 µM CoCl2 on 5th passage cells in a conventional incubator (37°C; 5CO2). Then, immunofluorescence of HIF-1α and mTOR was done. Data was analyzed statistically using One-way ANOVA and Tukey's HSD. Results: Significant differences were found between normoxic and hypoxic groups on HIF-1α (p=0.015) and mTOR (p=0.000) expressions. The highest HIF-1α expression was found at 48 hours in the hypoxia group, while for mTOR at 24 hours in the hypoxia group. Conclusion: Hypoxia using cobalt chloride was able to increase human umbilical cord mesenchymal stem cells expression of HIF-1α and mTOR.

Determination of cobalt and tungsten in human urine by inductively coupled plasma mass spectrometry / 中华劳动卫生职业病杂志

Objective: To establish a inductively coupled plasma mass spectrometry method for the determination of trace cobalt and tungsten in human urine. Methods: The authors used 1% nitric acid solution as diluent in October-December 2021, the sample dilution factor and internal standard element were optimized by single factor rotation experiment, and the difference between the working curve and the standard curve was compared. Results: The method uses working curve to determine cobalt and tungsten in urine, the linear range of this method was 0.0~10.0 μg/L, the correlation coefficient was 0.999 9, the detection limits respectively were 0.005 μg/L (cobalt) and 0.09 μg/L (tungsten), the recoveries of samples respectively were 87.0%~100.2% (cobalt) and 89.4%~104.8% (tungsten), the relative standard deviations respectively were 0.4%~4.4% (cobalt) and 0.6%~3.8% (tungsten) . Conclusion: A simple and rapid method for determination of cobalt and tungsten in urine has been established. This method has the advantages of simple operation, high sensitivity, low detection limit and good stability. It is suitable for determination of cobalt and tungsten in urine of all kinds of people.

Desenvolvimento de compostos de coordenação para aplicação foliar e elucidação do mecanismo de absorção / Development of coordination compounds for foliar application and elucidation of the absorption mechanism

O objetivo geral desse trabalho foi desenvolver compostos de coordenação com os metais cobre, manganês, zinco, cobalto, níquel e magnésio com os aminoácidos L- ácido aspártico e glutâmico para aplicação como fertilizantes foliares e elucidação de seus prováveis mecanismos de absorção pela planta. Como plano de trabalho, pretendeu-se produzir alguns complexos metálicos com agentes complexantes que confiram características específicas: alta estabilidade termodinâmica e cinética quando comparado a quelatos usados comercialmente dos mesmos metais; alta solubilidade; compatibilidade com herbicidas e fungicidas e alta estabilidade frente a variações de pH. Os compostos foram caracterizados no estado sólido e/ou em solução aquosa, através de técnicas disponíveis em nosso laboratório, na Central Analítica do IQ-USP e/ou nos laboratórios da ICL América do Sul Ind. e Com. SA. Com o desenvolvimento dos compostos de coordenação, foram avaliados alguns parâmetros considerados imprescindíveis para garantia da qualidade do produto gerado, que foram então comparados aos de quelatos de EDTA (ácido etilenodiaminotetraacético) comercializados atualmente e que demonstraram vantagens. Para avaliar a eficiência dos produtos gerados foi realizada aplicação foliar em ao menos uma cultura e verificado o teor de cada nutriente após período de absorção e resposta produtiva, evidenciando e determinando o mecanismo de absorção realizado pela planta. Como resultado, desenvolveu-se uma série de produtos com alta tecnologia agregada que trouxeram benefícios nutricionais, sustentando uma nutrição de qualidade além de serem ecologicamente favoráveis (eco-friendly portfolio)

This project aims the development of copper, manganese, zinc, cobalt, nickel and iron metal complexes with L-amino acids aspartic and glutamic acids for application as foliar fertilizers and elucidation of the probable incorporation/absorption mechanism by plants. As a work plan, it was intended to produce these metal complexes with complexing agents that provide specific characteristics: high thermodynamic and kinetic stabilities when compared to the corresponding EDTA chelates; high solubility; compatibility with herbicides and fungicides and high stability against pH variations. With the development of such coordination compounds, some parameters considered indispensable to quality assurance were then evaluated, in comparison to that of currently available commercial EDTA chelates. To evaluate the performance of the obtained compounds, two foliar applications in the same crop were carried out. Further, the content of each nutrient after the production period and the productive capacity were evaluated, aiming to elucidate the absorption mechanism of the plant. As a result, elaborated products with high added technology were obtained, capable of ameliorating the nutritional benefits, that can support an eco-friendly portfolio

Thermal expansion and corrosion resistance of cobalt-chromium alloys fabricated by contemporary manufacturing processes: an in vitro study / Expansión térmica y resistencia a la corrosión de aleaciones de cobalto-cromo fabricadas mediante procesos de abricación contemporáneos: un estudio in vitro

In Purpose: The fabrication technique can influence the mechanical properties of Cobalt-Chromium (Co-Cr) dental alloys. Hence, the present study aims to determine the corrosion resistance and thermal expansion of alloys manufactured using three contemporary techniques. Material and Methods: A total of nine specimens of Co-Cr alloy were prepared according to ISO 22674 by each one of the three manufacturing processes (three in each process); conventional casting, direct metal laser sintering (DMLS) and milling (MIL). All these specimens were tested for coefficient of thermal expansion and corrosion resistance. The data was tabulated and analyzed statistically. Results: The difference in the thermal expansion of alloys fabricated using three techniques was non-significant at almost all the temperatures from 50 ºC to 950 ºC (p>0.05), except 450 ºC and 600 °C. The polarization resistance of specimens manufactured using the conventional method was more compared to DMLS and MIL at pH 5 (Conventional>MIL>DMLS) (p<0.001). Conclusion: The thermal expansion behavior of alloys manufactured using the three selected techniques were similar, whereas, at acidic pH, the corrosion resistance of conventional and MIL were better than the DMLS.

Antecedentes: La técnica de fabricación puede influir en las propiedades mecánicas de las aleaciones dentales de cobalto-cromo (Co-Cr). Por lo tanto, el presente estudio tiene como objetivo determinar la resistencia a la corrosión y la expansión térmica de aleaciones fabricadas con tres técnicas contemporáneas. Material y Métodos: Se prepararon un total de nueve probetas de aleación de Co-Cr según ISO 22674 por cada uno de los tres procesos de fabricación (tres en cada proceso); fundición convencional, sinterización directa de metal por láser (DMLS) y fresado (MIL). Todos estos especímenes fueron probados para determinar el coeficiente de expansión térmica y la resistencia a la corrosión. Los datos fueron tabulados y analizados estadísticamente. Resultados: La diferencia en la dilatación térmica de las aleaciones fabricadas con las tres técnicas no fue significativa en casi todas las temperaturas desde 50ºC hasta 950ºC (p>0,05), excepto 450ºC y 600ºC. La resistencia a la polarización de las muestras fabricadas con el método convencional fue mayor en comparación con DMLS y MIL a pH 5 (Convencional>MIL>DMLS) (p<0, 0 01). Conclusión: El comportamiento de expansión térmica de las aleaciones fabricadas con las tres técnicas seleccionadas fue similar, mientras que, a pH ácido, la resistencia a la corrosión de la convencional y la MIL fue mejor que la de la DMLS.

Sex differences in the link between blood cobalt concentrations and insulin resistance in adults without diabetes

BACKGROUND@#Little is known about the effects of environmental cobalt exposure on insulin resistance (IR) in the general adult population. We investigated the association between cobalt concentration and IR.@*METHODS@#A total of 1281 subjects aged more than 20 years with complete blood cobalt data were identified from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 cycle. Blood cobalt levels were analyzed for their association with IR among all populations and subgroups by sex. Regression coefficients and 95% confidence intervals (CIs) of blood cobalt concentrations in association with fasting glucose, insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were estimated using multivariate linear regression after adjusting for age, sex, ethnicity, alcohol consumption, body mass index, education level, and household income. A multivariate generalized linear regression analysis was further carried out to explore the association between cobalt exposure and IR.@*RESULTS@#A negative association between blood cobalt concentration (coefficient = - 0.125, 95% CI - 0.234, - 0.015; P = 0.026) and HOMA-IR in female adults in the age- and sex-adjusted model was observed. However, no associations with HOMA-IR, fasting glucose, or insulin were found in the overall population. In the generalized linear models, participants with the lowest cobalt levels had a 2.74% (95% CI 0.04%, 5.50%) increase in HOMA-IR (P for trend = 0.031) compared with subjects with the highest cobalt levels. Restricted cubic spline regression suggested that a non-linear relationship may exist between blood cobalt and HOMA-IR.@*CONCLUSIONS@#These results provide epidemiological evidence that low levels of blood cobalt are negatively associated with HOMA-IR in female adults.

Effects of 3 kinds of processing techniques on the fitness of metal clasp / 中南大学学报(医学版)

OBJECTIVES@#At present, removable partial denture is still one of the main restoration methods for dentition defects. However, the trend for digital partial denture is becoming more and more obvious in the field of oral repair. However, there are relatively few studies on digital removable partial denture. The aim of this study is to investigate the effects of 3 processing technologies (precision casting, digital cutting, and 3D printing) on the fitness for the clasps of cobalt chromium alloy and pure titanium removable partial denture, and to provide a theoretical basis for the clinical application of digital removable partial denture.@*METHODS@#Clasps of Co-Cr alloy and pure titanium were produced by 3 different processing technologies (precision casting, digital cutting, and 3D printing). There are 6 groups, including a casting pure titanium group, a casting cobalt chromium group, a cutting pure titanium group, a cutting cobalt chromium group, a printing pure titanium group, and a printing cobalt chromium group (@*RESULTS@#There was no statistical difference in fitness between the casting pure titanium group and the casting cobalt chromium group (@*CONCLUSIONS@#The cobalt chromium alloy and pure titanium clasps made by precision casting, digital cutting, and 3D printing have good fitness. Under the same process, there is no significant difference between cobalt chromium alloy and pure titanium clasps. The 3D printing pure titanium clasps have better fitness than casting pure titanium and cutting pure titanium clasps, which meet the needs of clinical application.

Characterization and evaluation of the enzymatic activity of tetanus toxin submitted to cobalt-60 gamma radiation

Tetanus toxin blocks the release of the inhibitory neurotransmitters in the central nervous system and causes tetanus and its main form of prevention is through vaccination. The vaccine is produced by inactivation of tetanus toxin with formaldehyde, which may cause side effects. An alternative way is the use of ionizing radiation for inactivation of the toxin and also to improve the potential immunogenic response and to reduce the post-vaccination side effects. Therefore, the aim of this study was to characterize the tetanus toxin structure after different doses of ionizing radiation of 60Co. Methods Irradiated and native tetanus toxin was characterized by SDS PAGE in reducing and non-reducing conditions and MALD-TOF. Enzymatic activity was measured by FRET substrate. Also, antigenic properties were assessed by ELISA and Western Blot data. Results Characterization analysis revealed gradual modification on the tetanus toxin structure according to doses increase. Also, fragmentation and possible aggregations of the protein fragments were observed in higher doses. In the analysis of peptide preservation by enzymatic digestion and mass spectrometry, there was a slight modification in the identification up to the dose of 4 kGy. At subsequent doses, peptide identification was minimal. The analysis of the enzymatic activity by fluorescence showed 35 % attenuation in the activity even at higher doses. In the antigenic evaluation, anti-tetanus toxin antibodies were detected against the irradiated toxins at the different doses, with a gradual decrease as the dose increased, but remaining at satisfactory levels. Conclusion Ionizing radiation promoted structural changes in the tetanus toxin such as fragmentation and/or aggregation and attenuation of enzymatic activity as the dose increased, but antigenic recognition of the toxin remained at good levels indicating its possible use as an immunogen. However, studies of enzymatic activity of tetanus toxin irradiated with doses above 8 kGy should be further analyzed.(AU)

Cobalt deficiency in cattle and its impact on production / Deficiência de cobalto em bovinos e seu impacto na produção

Two outbreaks of cobalt deficiency in beef cattle were diagnosed in Midwestern Brazil. We discuss the clinical, epidemiological, pathological features, therapeutic measures, and impact aspects of the production system associated with these outbreaks occurring outbreaks in two farms of extensive cattle raising-system in the state of Mato Grosso do Sul. Seven affected cattle were euthanized and necropsied. Tissues for histopathology and microelements dosage were secured. At Farm A, 3100 cattle of all ages got sick, and 396 died; at Farm B, 148 were affected, and 110 died. In both farms, cattle were fed the same mineral supplement. The main clinical signs were weight loss and weakness, even though a good supply of forage was available in the paddocks. Many cattle stop grazing and chew at tree barks, wood chips from fence posts, and bones. In addition to the deaths, there was a compromised growth, and the reproductive rates fell sharply. The necropsied cattle were thin, with rough hair coat and pale mucous membranes. The liver was diffusely orange and showed a lobular pattern. The bone marrow was gelatinous and diffusely yellow. Histological changes included hemosiderosis in the liver and spleen, hepatocellular vacuolar degeneration, and myeloid and erythroid hypoplasia of the bone marrow. In the white matter of four cattle's brains, the myelin sheath was markedly distended (spongy degeneration). Proliferative parasitic abomasitis was observed in three cattle. The presumptive diagnosis was based on the association of the clinical picture, the necropsy findings, and the ruling out of other possible causes. The diagnosis was confirmed by the favorable response to treatment with cobalt and vitamin B12 orally and by mineral supplementation.(AU)

Dois surtos de deficiência de cobalto em bovinos de corte foram diagnosticados. Os aspectos clínicos, epidemiológicos, anatomopatológicos, terapêuticos e impactos no sistema de produção são descritos e discutidos. Os surtos ocorreram em duas fazendas de criação extensiva estado de Mato Grosso do Sul, Centro-Oeste brasileiro. Sete bovinos afetados foram eutanasiados e necropsiados. Na necropsia foram colhidas amostras para exames histopatológicos e dosagem de microelementos. Na Fazenda A, 3100 bovinos de todas as idades adoeceram e 396 morreram e na Fazenda B, 148 bovinos adoeceram e 110 morreram. Ambas as fazendas utilizavam o mesmo suplemento mineral. Os principais sinais clínicos observados foram emagrecimento e fraqueza, apesar da boa oferta de forragem nos piquetes, muitos bovinos deixaram de pastejar e comiam cascas de árvores, madeira das porteiras e ossos. Além das mortes, tiveram crescimento comprometido e os índices reprodutivos tiveram queda acentuada. Os bovinos necropsiados estavam magros, com os pelos arrepiados e mucosas pálidas. O fígado estava difusamente alaranjado e com evidenciação do padrão lobular. A medula óssea estava de consistência gelatinosa e difusamente amarelada. Alterações histológicas incluíam degeneração vacuolar hemossiderose que era moderada no fígado e marcada no baço. Hipoplasia mieloide e eritoide era vista na medula óssea. Na substância branca do encéfalo de quatro bovinos, a bainha de mielina estava marcadamente distendida (degeneração esponjosa). Abomasite parasitária proliferativa foi observada em três bovinos. O diagnóstico presuntivo baseou-se na associação do quadro clínico, nos achados de necropsia e na eliminação de outras possíveis causas. O diagnóstico foi confirmado pela resposta favorável ao tratamento com cobalto e vitamina B12 por via oral, e a suplementação mineral.(AU)

Association between metal cobalt exposure and the risk of congenital heart defect occurrence in offspring: a multi-hospital case-control study

BACKGROUND@#Many studies have investigated heavy metal exposure could increase the occurrence of congenital heart defects (CHDs). However, there are limited data regarding the relationship between cobalt exposure and CHD occurrence in offspring. The aim of this study was to analyze the association between cobalt exposure in mothers and the risk of CHDs in offspring.@*MATERIALS AND METHODS@#In order to explore the association between cobalt exposure and occurrence of congenital heart defect (CHD), a case-control study with 490 controls and 399 cases with CHDs in China were developed. The concentrations of cobalt in hair of pregnant woman and fetal placental tissue were measured and processed by a logistic regression analysis to explore the relationship between cobalt exposure and risk of CHDs.@*RESULTS@#The median concentration of hair cobalt in the control and case group was 0.023 ng/mg and 0.033 ng/mg (aOR, 1.837; 95% CI, 1.468-2.299; P < 0.001), respectively. And the median (5-95% range) fetal placental cobalt concentrations were 19.350 ng/g and 42.500 ng/g (aOR, 2.924; 95% CI, 2.211-3.868; P < 0.001) in the control and case groups, respectively. Significant differences in the middle level of cobalt in hair were found in the different CHD subtypes, including septal defects, conotruncal defects, right ventricular outflow tract obstruction, and left ventricular outflow tract obstruction (P < 0.001). Dramatically, different cobalt concentrations in fetal placental tissue were found in all subtypes of cases with CHDs (P < 0.01).@*CONCLUSIONS@#The finding suggested that the occurrence of CHDs may be associated with cobalt exposure.

Avaliação da citotoxicidade e resposta tecidual de soluções irrigadoras experimentais a partir de biovidro e biovidro modificado com cobalto / Evaluation of cytotoxicity and tissue response of experimental irrigating solutions from bioglass and bioglass modified with cobalt

Introdução: Novas formulações de materiais vítreos apresentaram atividade antimicrobiana e osteoindutora. Objetivos: O objetivo deste estudo foi avaliar a citotoxicidade e a biocompatibilidade de soluções produzidas a partir de novas formulações de biovidros, o F18 (biovidro experimental) e o F18 com Cobalto (F18-Co; biovidro experimental dopado com cobalto), comparadas à água de cal, obtida a partir de solução com hidróxido de cálcio (Ca(OH)2). Material e métodos: O F18 foi preparado e moído, e parte deste foi dopada com cobalto. As soluções foram preparadas com cada material (1:10 de pó para água), formando os grupos F18, F18-Co e Ca(OH)2. Células L929 foram cultivadas, e a viabilidade celular avaliada a partir das soluções e de suas diluições (½, », 1/8 e 1/16 diluição) pelo teste MTT, após 24 e 48 horas. Para avaliar a biocompatibilidade, tubos de polietileno foram preenchidos com esponjas de fibrina embebidas nas soluções não diluídas, e tubos embebidos em soro fisiológico serviram de controle. Os tubos foram implantados no dorso de 16 ratos. Após 7 e 30 dias (n = 8), os ratos foram eutanasiados, e os tubos com o tecido circundante foram processados para coloração de hematoxilina-eosina (H.E.) e análise da inflamação através de escores. Os dados paramétricos (citotoxicidade) foram submetidos aos testes de normalidade para definir o teste estatístico a ser empregado, e os dados não-paramétricos (H.E.), foram avaliados pelos testes de Kruskal Wallis e Dunn (p < 0,05). Resultados: As soluções não diluídas dos materiais, e as diluições de ½ e », reduziram a viabilidade celular em 24 h (p < 0,05). As diluições de 1/8 e 1/16 do F18 e F18Co apresentaram viabilidade celular semelhante ao controle (p > 0,05), o que não ocorreu com Ca(OH)2 (p < 0,05), que foi citotóxico. Em 48 h, apenas as soluções não diluídas e diluições de ½ e » do F18 foram similares ao controle (p > 0,05), e as demais foram citotóxicas. Mas as diluições de 1/8 e 1/16 do F18Co teve um aumento na viabilidade celular comparadas às soluções do Ca(OH)2 (p < 0,05), e foram semelhantes ao controle (p > 0,05). Aos 7 dias, controle, F18 e F18-Co apresentaram inflamação moderada, e Ca(OH)2, severa (p > 0,05); a cápsula fibrosa foi espessa. Aos 30 dias, controle e F18-Co apresentaram inflamação leve comparados ao F18, com inflamação moderada (p < 0,05); Ca(OH)2 teve inflamação leve ( p > 0,05); a cápsula fibrosa foi fina na maior parte dos espécimes . Conclusões: Soluções experimentais de F18 e F18 dopado com cobalto são citocompatíveis, diferentemente da solução de Ca(OH)2; todas as soluções apresentaram biocompatibilidade(AU)

Introduction: New formulations of vitreous materials showed antimicrobial and osteoinductive activity. Objectives: The aim of this study was to evaluate the cytotoxicity and biocompatibility of solutions produced from new formulations of bioglass, F18 (experimental bioglass) and F18 with Cobalt (F18-Co; experimental bioglass doped with cobalt), compared to lime water, obtained from a solution with calcium hydroxide (Ca(OH)2). Material and methods: The F18 was prepared and ground, and part of it was doped with cobalt. The solutions were prepared with each material (1:10 powder to water), forming groups F18, F18-Co and Ca(OH)2. L929 cells were cultured, and cell viability assessed from solutions and from its dilutions (½, », 1/8 and 1/16 dilution) by the MTT test, after 24 and 48 hours. For biocompatibility analysis, polyethylene tubes were filled with fibrin sponges embedded in the non-diluted solutions, and tubes embedded in saline solution served as controls. The tubes were implanted on the dorsum of 16 rats. After 7 and 30 days (n = 8), the rats were euthanized, and the tubes with the surrounding tissue were processed for staining of hematoxylin-eosin (H.E.) and analysis of inflammation through scores. The parametric data (cytotoxicity) were subjected to normality tests to define the statistical test to be used, and the nonparametric data (H.E.), were evaluated by the Kruskal Wallis and Dunn tests (p < 0.05). Results: Undiluted solutions of the materials, and dilutions of ½ and », reduced cell viability in 24 h (p < 0.05). The 1/8 and 1/16 dilutions of F18 and F18-Co showed cell viability similar to the control (p > 0.05), which did not occur with Ca(OH)2 (p <0.05), which was cytotoxic. At 48 h, only undiluted solutions and dilutions of ½ and » of F18 were similar to the control (p > 0.05), and the others were cytotoxic. However, the 1/8 and 1/16 dilutions of F18-Co had an increase in cell viability compared to Ca(OH)2 solutions (p <0.05), and were similar to the control (p > 0.05). At 7 days, control, F18 and F18-Co showed moderate inflammation, and Ca(OH)2, severe (p > 0.05); the fibrous capsule was thick. At 30 days, control and F18-Co showed mild inflammation compared to F18, with moderate inflammation (p < 0.05); Ca(OH)2 had mild inflammation (p > 0.05); the fibrous capsule was thin in most specimens. Conclusions: Experimental solutions of F18 and F18 doped with cobalt are cytocompatible, unlike the Ca(OH) 2 Keywords: solution; all solutions showed biocompatibility(AU)

Dermatite de contato por corticoide em pacientes com dermatite atópica / Corticosteroid contact dermatitis in patients with atopic dermatitis

Objetivo: Avaliar a sensibilização a corticoides tópicos e substâncias do teste de contato padrão e cosméticos em pacientes com dermatite atópica (DA) no Serviço de Alergia e Imunologia do HSPE-SP. Método: Estudo retrospectivo com análise de prontuário de pacientes com DA, classificados de acordo com o SCORing Atopic Dermatitis (SCORAD) em leve, moderada e grave, que foram atendidos no ambulatório de Alergia e Imunologia do HSPE-SP, submetidos a teste de contato com baterias padrão, cosméticos, corticoides, incluindo furoato de mometasona. Resultados: Após análise estatística dos dados de 51 pacientes portadores de DA, foi identificada maior prevalência no gênero feminino (73%). Pacientes com DA moderada/grave apresentaram maior positividade (62%) para pelo menos uma substância. Foram mais propensos a positivar para teste de contato, pacientes maiores de 18 anos. As substâncias que foram mais positivas na bateria padrão foram: sulfato de níquel (33%), neomicina (10%), e bicromato de potássio e cloreto de cobalto (8% cada). O sulfato de níquel foi mais positivo no gênero feminino. Três (5,9%) pacientes apresentaram positividade para teste de contato com bateria de corticoides, sendo positivas substâncias betametasona 1%, budesonida 0,01% e butirato de hidrocortisona 1%, e todos eram portadores de DA leve. Foi identificada relação entre positividade para bateria de corticoides e sulfato de níquel. Conclusão: Os testes de contato foram mais positivos em adultos. Houve maior sensibilidade para o sulfato de níquel no gênero feminino. Sensibilidade importante à neomicina na DA moderada/grave. Pacientes com alergia de contato por corticoides podem apresentar alergia a sulfato de níquel. Esse trabalho chama atenção para a porcentagem importante de pacientes com DA acometidos por alergia de contato por corticoides, sendo esse tipo alergia um problema emergente e que tem sido cada vez mais relatado na última década; porém, ainda são escassos os estudos envolvendo esse assunto.

Objective: To evaluate sensitization to topical corticosteroids and standard patch testing substances in patients with atopic dermatitis (AD) at the HSPE-SP Allergy and Immunology Department. Methods: This retrospective study assessed medical records of patients with AD, whose severity was classified as mild, moderate or severe according to SCORing Atopic Dermatitis (SCORAD). They were seen at the HSPE-SP Allergy and Immunology outpatient clinic and underwent a patch test with the following series: standard, cosmetics, and corticosteroids, including mometasone furoate. Results: After statistical analysis of data from 51 patients with AD, a higher prevalence was identified in female participants (73%). Patients with moderate-to-severe AD had more positive results (62%) for at least one substance. Patients older than 18 years were more likely to be positive in the patch test. The substances that were most frequently positive in the standard series were nickel sulfate (33%), neomycin (10%) and potassium dichromate and cobalt chloride (8% each). Positive nickel sulfate was more common in female participants. Three (5.9%) patients were positive for corticosteroids (1% betamethasone, 0.01% budesonide and 1% hydrocortisone butyrate) and all had mild AD. A relationship between positivity for corticosteroid series and nickel sulfate was identified. Conclusion: Patch tests were more frequently positive in adults. There was higher sensitivity to nickel sulfate in female patients. There was important sensitivity to neomycin in patients with moderate-to-severe AD. Patients with corticosteroid contact allergy may present with allergy to nickel sulfate. This paper draws attention to the important percentage of patients with AD affected by corticosteroid contact allergy, which has become an emerging problem that has been increasingly reported in the past decade. However, there are still few studies addressing this topic.

Extracts of Celastrus Orbiculatus Inhibit Cancer Metastasis by Down-regulating Epithelial-Mesenchymal Transition in Hypoxia-Induced Human Hepatocellular Carcinoma Cells / 中国结合医学杂志

OBJECTIVE@#To evaluate the effects of Celastrus Orbiculatus extracts (COE) on metastasis in hypoxia-induced hepatocellular carcinoma cells (HepG2) and to explore the underlying molecular mechanisms.@*METHODS@#The effect of COE (160, 200 and 240 µ g/mL) on cell viability, scratch-wound, invasion and migration were studied by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT), scratch-wound and transwell assays, respectively. CoCl was used to establish a hypoxia model in vitro. Effects of COE on the expressions of E-cadherin, vimentin and N-cadherin were investigated with Western blot and immunofluorescence analysis, respectively.@*RESULTS@#COE inhibited proliferation and metastasis of hypoxia-induced hepatocellular carcinoma cells in a dose-dependent manner (P<0.01). Furthermore, the expression of epithelial-mesenchymal transition (EMT) related markers were also remarkably suppressed in a dose-dependent manner (P<0.01). In addition, the upstream signaling pathways, including the hypoxia-inducible factor 1 α (Hif-1 α) and Twist1 were suppressed by COE. Additionally, the Hif-1 α inhibitor 3-5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), potently suppressed cell invasion and migration as well as expression of EMT in hypoxia-induced HepG2 cells. Similarly, the combined treatment with COE and YC-1 showed a synergistic effect (P<0.01) compared with the treatment with COE or YC-1 alone in hypoxia-induced HepG2 cells.@*CONCLUSIONS@#COE significantly inhibited the tumor metastasis and EMT by suppressing Hif-1 α/Twist1 signaling pathway in hypoxia-induced HepG2 cell. Thus, COE might have potential effect to inhibit the progression of HepG2 in the context of tumor hypoxia.

Follow-up of Metal-on-Metal Hip Replacements at a Large District Hospital and the Implementation of Medicines and Healthcare Products Regulatory Agency Guidelines: A Review of 297 Patients

BACKGROUND: Medicines and Healthcare products Regulatory Agency (MHRA) guidance for patients with metal-on-metal (MoM) hip replacements was provided in 2012 and updated in 2017 to assist in the early detection of soft-tissue reactions due to metal wear debris. A large number of MoM hip replacements were undertaken at our hospital trust. A program of recall for all patients with MoM hip replacements was undertaken and MHRA guidelines were implemented. In this study, we aimed to investigate the effectiveness of the revised MHRA guidelines in the detection of early adverse reactions to metal debris and to re-evaluate the indications for metal artifact reduction sequence magnetic resonance imaging (MARS-MRI) and revision surgery. METHODS: Identification and recall of all patients with MoM hip replacements from 2001 were conducted by using theatre logs, patient records, clinical coding information, and consultant logbooks. Two senior arthroplasty consultants reviewed X-rays and patient records. Postal questionnaires were forwarded to patients, together with requests for general practitioners to complete cobalt and chromium blood tests. The two consultant-led review of MOM replacements was undertaken with further radiological investigations (X-rays, MARS-MRI) performed according to the 2017 guidance with support of consultant radiologists. RESULTS: Of 674 identified patients, 297 were available for review: 26 patients did not have MoM implants, 36 were untraceable, 59 refused follow-up, 87 moved out of area, 147 had died, and 22 already had revision. Of 297 patients, 126 were women and 171 were men; age range was 39 to 95 years (mean age, 69 years); 126 had resurfacing and 171 had MoM replacements. Twenty-six patients had elevated metal ions. Thirty-three patients underwent MARS-MRI: MARS-MRI results were positive in 17 and negative in 16. Of 17 patients with positive MARS-MRI, 10 patients were asymptomatic and seven were waiting revision. CONCLUSIONS: Positive MARS-MRI can often occur in the absence of elevated metal ion levels; elevated blood metal ion levels do not mean MARS-MRI will be positive. All patients with MoM replacements were at risk. It is imperative to assess patients regularly for symptoms that may raise clinical suspicion and maintain a low threshold to performing MARS-MRI.

A Clinical Study Including Patch Test of Rosacea Patients / 대한피부과학회지

BACKGROUND: Rosacea is a relatively common inflammatory skin disease characterized by central facial erythema that persists for several months or longer. Experimental studies have demonstrated that rosacea compromises the epidermal barrier protection against allergens and irritants, rendering rosacea patients susceptible to contact hypersensitivity and skin irritation. OBJECTIVE: This study aimed to investigate allergic and irritant reactions to topical agents and cosmetics in rosacea patients using patch tests. METHODS: Rosacea signs and subtypes of 40 patients were recorded and subjective symptoms and clinical experiences related to topical agents and cosmetics were assessed using a questionnaire. Patch tests were performed in these patients using the Korean Standard Series (Chemotechnique Diagnostics, Sweden), the TRUE test® (Mekos Laboratories ApS, Denmark), and 26 selected fragrance and 31 cosmetic antigens (TROLAB, Germany). RESULTS: Of 40 patch-tested patients, 26 (65%) showed at least 1 positive reaction and 13 (32.5%) showed 2 or more positive reactions. The most common allergens were nickel (II) sulfate (50%), cobalt chloride (10%), epoxy resin (7.7%), and thimerosal (7.5%). Thirteen patients (32.5%) experienced irritant patch test reactions. There were no significant differences in allergic or irritant positive reactions between mild, moderate, and severe cases of rosacea or between rosacea subtypes. Irritant reactions were more common in fair-skinned participants. CONCLUSION: Different topical medications are used in the treatment of rosacea patients. Exacerbation of rosacea may be caused by a hypersensitivity reaction or irritation induced by the topical agent or by cosmetics.

Quantitative Analysis of Metal Contents in Korean Herbs and Herbal Products to Give Advice for Metal Allergic Patient

BACKGROUND: Herbs have been used worldwide as complementary and alternative medicines. In Korea, herbs for medical purpose are strictly controlled by the Korea Food and Drug Administration (KFDA). But it does not provide standards for metal antigens. OBJECTIVE: This study conducted to identify the metal contents of Korean herbs and herbal products and to give information on counselling metal allergic patient. METHODS: The concentration of three metal allergens with high antigenicity, cobalt (Co), chromium (Cr), nickel (Ni) was quantitatively determined using inductively coupled plasma with a mass spectrometer after nitric acid (HNO₃) digestion. The herbal objects are as follows: 1) ten kinds of herb plants, 2) ten herbal products sold in Korean drugstores, and 3) ten herbal extracts prescribed by Korean herbal doctors. RESULTS: In 30 samples, Ni and Cr were detected in all items. Co was not detected in two drugstore products. CONCLUSION: Although the levels of metal detected in this study were very low relative to international guidelines and KFDA regulations, the herbal preparations contained similar or higher metal levels than known metal-rich foods. It can cause problems when it added to the daily diet and cause deterioration of skin lesions of metal sensitized person.

Effects of heme oxygenase-1 upregulation on isoproterenol-induced myocardial infarction

The present study was designed to examine the effect of heme oxygenase-1 (HO-1) induction by cobalt protoporphyrin (CoPP) on the cardiac functions and morphology, electrocardiogram (ECG) changes, myocardial antioxidants (superoxide dismutase [SOD] and glutathione [GSH]), and expression of heat shock protein (Hsp) 70 and connexin 43 (Cx-43) in myocardial muscles in isoproterenol (ISO) induced myocardial infarction (MI). Thirty two adult male Sprague Dawely rats were divided into 4 groups (each 8 rats): normal control (NC) group, ISO group: received ISO at dose of 150 mg/kg body weight intraperitoneally (i.p.) for 2 successive days; ISO + Trizma group: received (ISO) and Trizma (solvent of CoPP) at dose of 5 mg/kg i.p. injection 2 days before injection of ISO, with ISO at day 0 and at day 2 after ISO injections; and ISO + CoPP group: received ISO and CoPP at a dose of 5 mg/kg dissolved in Trizma i.p. injection as Trizma. We found that, administration of ISO caused significant increase in heart rate, corrected QT interval, ST segment, cardiac enzymes (lactate dehydrogenase, creatine kinase-muscle/brain), cardiac HO-1, Hsp70 with significant attenuation in myocardial GSH, SOD, and Cx-43. On the other hand, administration of CoPP caused significant improvement in ECG parameters, cardiac enzymes, cardiac morphology; antioxidants induced by ISO with significant increase in HO-1, Cx-43, and Hsp70 expression in myocardium. In conclusions, we concluded that induction of HO-1 by CoPP ameliorates ISO-induced myocardial injury, which might be due to up-regulation of Hsp70 and gap junction protein (Cx-43).

Propofol protects human cardiac AC16 cells from CoCl2-induced hypoxic injury / 中南大学学报(医学版)

To explore the effect of propofol on human cardiac AC16 cells under CoCl2-induced hypoxic injury and the possible mechanisms.
 Methods: Human AC16 cardiomyocytes were treated with cobalt chloride (CoCl2) to mimic hypoxic condition in cultured cardiomyocytes. The AC16 cells were divided into 3 groups: a control group, a CoCl2 hypoxia group (CoCl2 group), and a propofol+CoCl2 group (propofol+ CoCl2 group). The cell viability was assessed by cell counting kit-8 (CCK-8). Cell apoptosis ratio (AR) and the mitochondrial membrane potential (Δψm) were detected by flow cytometry. The reactive oxygen species (ROS) production in AC16 cells were determined with the ROS-sensitive fluorescent probe. Meanwhile, total intracellular levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in AC16 cells were detected with commercially available kits. Western blot was used to evaluate the activation of c-Jun N-terminal kinase (JNK) and p38 signaling pathways.
 Results: 1) Compared with the control group, AC16 cell viability was decreased significantly in the CoCl2 group following the treatment with 500 μmol/L CoCl2 (P<0.01); 2) Compared with the control group, AR value in AC16 cells was increased significantly in the CoCl2 group, while Δψm was decreased significantly (all P<0.01). Compared with the CoCl2 group, AR value in AC16 cells was decreased significantly in the propofol+CoCl2 group, while Δψm was increased significantly (both P<0.05); 3) Compared with the control group, the levels of ROS and MDA were increased significantly, and the level of SOD was significantly decreased in the CoCl2 group (all P<0.01). Compared with the CoCl2 group, the ROS and MDA levels in the propofol+CoCl2 group were increased significantly and the SOD levels were decreased significantly (all P<0.05); 4) Compared with the control group, the phosphorylation levels of JNK and p38 were increased significantly (both P<0.05) in the CoCl2 group. Compared with the CoCl2 group, the phosphorylation levels of JNK and p38 were decreased significantly in the propofol+CoCl2 group (both P<0.05).
 Conclusion: The pretreatment with propofol may protect human cardiac AC16 cells from the chemical hypoxia-induced injury through regulation of JNK and p38 signaling pathways.

Biomonitoring of Metal Exposure During Additive Manufacturing (3D Printing)

BACKGROUND: Additive manufacturing (AM) is a rapidly expanding new technology involving challenges to occupational health. Here, metal exposure in an AM facility with large-scale metallic component production was investigated during two consecutive years with preventive actions in between.METHODS: Gravimetric analyzes measured airborne particle concentrations, and filters were analyzed for metal content. In addition, concentrations of airborne particles <300 nm were investigated. Particles from recycled powder were characterized. Biomonitoring of urine and dermal contamination among AM operators, office personnel, and welders was performed.RESULTS: Total and inhalable dust levels were almost all below occupational exposure limits, but inductively coupled plasma mass spectrometry showed that AM operators had a significant increase in cobalt exposure compared with welders. Airborne particle concentrations (<300 nm) showed transient peaks in the AM facility but were lower than those of the welding facility. Particle characterization of recycled powder showed fragmentation and condensates enriched in volatile metals. Biomonitoring showed a nonsignificant increase in the level of metals in urine in AM operators. Dermal cobalt and a trend for increasing urine metals during Workweek Year 1, but not in Year 2, indicated reduced exposure after preventive actions.CONCLUSION: Gravimetric analyses showed low total and inhalable dust exposure in AM operators. However, transient emission of smaller particles constitutes exposure risks. Preventive actions implemented by the company reduced the workers' metal exposure despite unchanged emissions of particles, indicating a need for careful design and regulation of the AM environments. It also emphasizes the need for relevant exposure markers and biomonitoring of health risks.

CoCl2 simulated hypoxia induce cell proliferation and alter the expression pattern of hypoxia associated genes involved in angiogenesis and apoptosis

BACKGROUND/AIMS: Hypoxia microenvironment plays a crucial role during tumor progression and it tends to exhibit poor prognosis and make resistant to various conventional therapies. HIF-1α acts as an important transcriptional regulator directly or indirectly associated with genes involved in cell proliferation, angiogenesis, apoptosis and energy metabolism during tumor progression in hypoxic microenvironment. This study was aimed to investigate the expression pattern of the hypoxia associated genes and their association during breast cancer progression under hypoxic microenvironment in breast cancer cells. METHODS: Cell proliferation in MCF-7 and MDA-MB-231 cell lines treated with different concentration of CoCl2 was analyzed by MTT assay. Flow cytometry was performed to check cell cycle distribution, whereas cell morphology was examined by phase contrast microscopy in both the cells during hypoxia induction. Expression of hypoxia associated genes HIF-1α, VEGF, p53 and BAX were determined by semiquantitative RT-PCR and real-time PCR. Western blotting was performed to detect the expression at protein level. RESULTS: Our study revealed that cell proliferation in CoCl2 treated breast cancer cells were concentration dependent and varies with different cell types, further increase in CoCl2 concentration leads to apoptotic cell death. Further, accumulation of p53 protein in response to hypoxia as compare to normoxia showed that induction of p53 in breast cancer cells is HIF-1α dependent. HIF-1α dependent BAX expression during hypoxia revealed that after certain extent of hypoxia induction, over expression of BAX conquers the effect of anti-apoptotic proteins and ultimately leads to apoptosis in breast cancer cells. CONCLUSION: In conclusion our results clearly indicate that CoCl2 simulated hypoxia induce the accumulation of HIF-1α protein and alter the expression of hypoxia associated genes involved in angiogenesis and apoptosis.

Cobalt chromium-Titanium rods versus Titanium-Titanium rods for treatment of adolescent idiopathic scoliosis; which type of rod has better postoperative outcomes?

SUMMARY OBJECTIVE; Compare the outcome of spinal deformity correction between Ti-Ti and CrCo-Ti rods for the treatment of spinal Adolescent Idiopathic Scoliosis (AIS) using rods mentioned with all pedicle screws and translation technique. METHOD; 59 patients operated for spinal deformity (Lenke 1 or 2) AIS. The patients were divided into two groups by random allocation using Ti-Ti rods (n = 29) and CrCo-Ti rods (n = 30) and the alone difference among them in the surgical procedure was rod material (Ti-Ti or CrCo-Ti rods) and finally, radiological outcomes were compared preoperatively, postoperatively and at last follow-up for 12 months. RESULTS; Patients' main curve correction after surgical procedure regardless type of rod was 48.95±11.04 (13-75) degree. Success rate of spinal deformity correction following surgical procedure regardless of type of administered rod was 86.76 ± 11.30 percent (62.5-100%). Mean of deformity correction rate was 91.49±10.67% using CrCo-Ti rods versus 81.86±9.88% using Ti-Ti rods (P-value=0.01). Angle change was 3.29±6.60 for kyphosis angle and 0.59±7.76 for lordosis angle. Rate of main curve correction was not significantly different considering patients' gender (P-value0.657). Main curve correction success rate was in association with patients' age and type of rod (P-value=0.054, r=-1.863 and P-value=0.001, r=8.865 respectively). CONCLUSION; CrCo-Ti rods have the ability to produce higher correction rates in AIS compared to Ti-Ti rod of the same diameter. CrCo-Ti rods provide significant and stable spinal correction, especially in correction of main curve. This rate was associated with patients' age and type of rod administered but not gender.

RESUMO OBJETIVO: Comparar o resultado da correção da deformidade da coluna vertebral com ligas de Ti-Ti e CrCo-Ti para o tratamento da Escoliose Idiopática do Adolescente (EIA) na coluna usando as ligas mencionadas com todos os parafusos pediculares e técnica de tradução. MÉTODO: 59 pacientes operados por EIA com deformidade da coluna vertebral (Lenke 1 ou 2). Os pacientes foram divididos em dois grupos por alocação aleatória usando ligas de Ti-Ti (n = 29) e ligas de CrCo-Ti (n = 30) e a única diferença entre eles no procedimento cirúrgico foi o material da liga (ligas de Ti-Ti ou CrCo-Ti) e, finalmente, resultados radiológicos foram comparados no pré-operatório, pós-operatório e no último retorno por 12 meses. RESULTADOS: A correção da curva principal do paciente após o procedimento cirúrgico, independentemente do tipo de liga, foi de 48,95±11,04 (13-75) graus. A taxa de sucesso da correção da deformidade da coluna vertebral após o procedimento cirúrgico, independentemente do tipo de liga administrada, foi de 86,76 ± 11,30% (62,5-100%). A média da taxa de correção da deformidade foi de 91,49±10,67% usando ligas de CrCo-Ti e 81,86±9,88% usando ligas de Ti-Ti (valor de P = 0,01). A mudança de ângulo foi de 3,29±6,60 para o ângulo de cifose e de 0,59±7,76 para o ângulo de lordose. A taxa de correção da curva principal não foi significativamente diferente considerando o sexo dos pacientes (Valor de P 0,657). A taxa de sucesso da correção da curva principal foi associada à idade do paciente e ao tipo de liga (valor de P=0,054, r=-1,863 e valor de P=0,001, r=8,865, respectivamente). CONCLUSÃO: As ligas de CrCo-Ti têm a capacidade de produzir taxas de correção mais altas em EIA em comparação com a liga de Ti-Ti do mesmo diâmetro. As ligas de CrCo-Ti fornecem uma correção espinhal significativa e estável, especialmente na correção da curva principal. Essa taxa foi associada à idade e ao tipo de liga administrada, mas não ao sexo.