Atropine does not prevent hypoxemia and bradycardia in tracheal intubation in the pediatric emergency department: observational study / O uso da atropina não previne hipoxemia e bradicardia na intubação traqueal no departamento de emergência pediátrica: estudo observacional

ABSTRACT Objective: The benefit of atropine in pediatric tracheal intubation is not well established. The objective of this study was to evaluate the effect of atropine on the incidence of hypoxemia and bradycardia during tracheal intubations in the pediatric emergency department. Methods: This is a single-center observational study in a tertiary pediatric emergency department. Data were collected on all tracheal intubations in patients from 31 days to incomplete 20 years old, performed between January 2016 and September 2020. Procedures were divided into two groups according to the use or not of atropine as a premedication during intubation. Records with missing data, patients with cardiorespiratory arrest, cyanotic congenital heart diseases, and those with chronic lung diseases with baseline hypoxemia were excluded. The primary outcome was hypoxemia (peripheral oxygen saturation ≤88%), while the secondary outcomes were bradycardia (decrease in heart rate >20% between the maximum and minimum values) and critical bradycardia (heart rate <60 bpm) during intubation procedure. Results: A total of 151 tracheal intubations were identified during the study period, of which 126 were eligible. Of those, 77% had complex, chronic underlying diseases. Atropine was administered to 43 (34.1%) patients and was associated with greater odds of hypoxemia in univariable analysis (OR: 2.62; 95%CI 1.15-6.16; p=0.027) but not in multivariable analysis (OR: 2.07; 95%CI 0.42-10.32; p=0.37). Critical bradycardia occurred in only three patients, being two in the atropine group (p=0.26). Bradycardia was analyzed in only 42 procedures. Atropine use was associated with higher odds of bradycardia in multivariable analysis (OR: 11.00; 95%CI 1.3-92.8; p=0.028). Conclusions: Atropine as a premedication in tracheal intubation did not prevent the occurrence of hypoxemia or bradycardia during intubation procedures in pediatric emergency.

RESUMO Objetivo: Avaliar o efeito da atropina na incidência de hipoxemia e bradicardia durante a intubação orotraqueal no departamento de emergência pediátrica. Métodos: Estudo observacional, realizado em departamento de emergência pediátrica terciário em que foram analisados os registros de intubações orotraqueais de pacientes com 31 dias a 20 anos incompletos, entre janeiro de 2016 e setembro de 2020. Os procedimentos foram divididos em dois grupos de acordo com o uso ou não da atropina como pré-medicação durante a intubação. Foram excluídos os procedimentos com falhas no preenchimento dos dados, pacientes com parada cardiorrespiratória, cardiopatias congênitas cianóticas, e aqueles com pneumopatias crônicas com hipoxemia basal. O desfecho primário foi hipoxemia (saturação periférica de oxigênio ≤88%), enquanto os desfechos secundários foram bradicardia (queda >20% entre a frequência cardíaca máxima e mínima) e bradicardia crítica (frequência cardíaca <60 bpm) durante o procedimento de intubação Resultados: Foram identificados 151 procedimentos de intubação orotraqueal, sendo 126 elegíveis para o estudo. Desses, 77% tinham doenças subjacentes complexas e crônicas. A atropina foi administrada em 43 (34,1%) pacientes e foi associada a maiores chances de hipoxemia na análise univariada (OR: 2,62; IC95% 1,15-6,16; p=0,027), porém, não na análise multivariada (OR: 2,073; IC95% 0,416-10,32; p=0,373). A bradicardia crítica ocorreu em apenas três pacientes, sendo dois no grupo atropina (p=0,268). A bradicardia foi analisada em apenas 42 procedimentos. O uso de atropina foi associado a maior probabilidade de bradicardia (OR: 11,00; IC95% 1,3-92,8; p=0,028) na análise multivariável. Conclusões: Atropina como pré-medicação na intubação orotraqueal não evitou a ocorrência de hipoxemia ou bradicardia durante os procedimentos de intubação na emergência pediátrica.

Tumor necrosis factor α-mediated low expression of fatty acid desaturase 2 in psoriasis / 中华皮肤科杂志

Objective:To investigate the expression of fatty acid desaturase 2 (FADS2) in psoriatic skin lesions, as well as its regulatory factors.Methods:FADS2 expression in psoriatic skin lesions was analyzed by using the dataset GDS4602 in Gene Expression Omnibus (GEO) database. Skin tissues were obtained from the back of 5 C57BL/6 mouse models of imiquimod-induced psoriasis, normal skin of 4 patients without psoriasis or other immune skin diseases, lesions of 4 patients with psoriasis before and after 10-week treatment with infliximab, as well as lesions of 3 patients with psoriasis before and after 12-week treatment with secukinumab in Shanghai Skin Disease Hospital. FADS2 expression was determined by both immunohistochemical staining and Western blot analysis in the epidermis of mouse skin tissues, and by immunohistochemical staining in that of human skin tissues. In vitro cultured human immortalized keratinocytes (HaCaT) were divided into several groups to be treated with 50 ng/ml tumor necrosis factor-α (TNF-α) alone for 0, 6, 12 and 24 hours respectively, 200 ng/ml interleukin-17A (IL-17A) alone for 0, 6 and 12 hours respectively, or treated with 50 ng/ml TNF-α and 5 μmol/L BAY 11-7082 (a nuclear factor-κB pathway inhibitor) for 6 hours (TNF-α+ BAY 11-7082 6 h group) , and the cells receiving normal culture served as the control group. After the above treatment, real-time fluorescence-based quantitative PCR (qPCR) and Western blot analysis were conducted to determine the mRNA and protein expression of FADS2 respectively. Statistical analysis was carried out by using one-way analysis of variance and t test. Results:Analysis of the dataset GDS4602 showed that the FADS2 mRNA expression was significantly lower in the lesional and non-lesional skin tissues from the patients with psoriasis (0.656 ± 0.475, 1.503 ± 1.062, respectively) than in the normal skin tissues (2.035 ± 1.226; F = 55.17, 3.07, P < 0.001, = 0.012, respectively) , and was significantly lower in the lesional skin tissues than in the non-lesional skin tissues from the patients with psoriasis ( F = 26.27, P < 0.001) . Western blot analysis and immunohistochemical staining both showed significantly decreased FADS2 protein expression in the mouse skin tissues in the imiquimod group (gray-value ratio: 0.463 ± 0.172; fluorescence intensity: 21.840 ± 3.125) compared with the normal control group (gray-value ratio: 1.000, t = 7.00, P = 0.002; fluorescence intensity: 30.720 ± 6.850, t = 3.15, P = 0.035) . Compared with the skin lesions before treatment, the FADS2 protein expression significantly increased in the skin lesions from the patients with psoriasis after 10-week treatment with infliximab (43.775± 3.342 vs. 27.950 ±1.218, t = -6.95, P = 0.006) , but was not significantly changed in the skin lesions from the patients with psoriasis after 12-week treatment with secukinumab (28.667 ± 3.402 vs. 31.933 ± 2.987, t = 2.72, P = 0.113) . qPCR revealed that the FADS2 mRNA expression significantly decreased in HaCaT cells in the TNF-α 6 h group and TNF-α 12 h group compared with the TNF-α 0 h group ( P = 0.002, 0.003, respectively) , while there was no significant change in the FADS2 mRNA expression in the IL-17A 6 h group and IL-17A 12 h group compared with the IL-17A 0 h group ( P = 0.849, 0.961, respectively) . The FADS2 mRNA expression significantly decreased in HaCaT cells in the TNF-α 6 h group (0.682 ± 0.132) compared with the control group (1.000, t = 4.82, P = 0.017) , but significantly increased in the TNF-α + BAY 11-7082 6 h group (1.541 ± 0.525) compared with the TNF-α 6 h group ( t = -3.58, P = 0.037) . Western blot analysis revealed significantly decreased FADS2 protein expression in HaCaT cells in the TNF-α 24 h group compared with the TNF-α 0 h group ( F = 6.24, P = 0.013) . Conclusion:FADS2 expression was downregulated in psoriatic lesions, which may be related to TNF-α.

Deficiency or activation of peroxisome proliferator-activated receptor α reduces the tissue concentrations of endogenously synthesized docosahexaenoic acid in C57BL/6J mice

BACKGROUND/OBJECTIVES: Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of α-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha (PPARα). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by PPARα. MATERIALS/METHODS: The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among PPARα homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate (PPARα agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA. RESULTS: PPARα ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, PPARα activation increased hepatic Acox, Fads1, Fads2 and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex. CONCLUSIONS: LCPUFA enzyme expression was altered by PPARα. Either PPARα deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.

Association between FADS1 rs174537 polymorphism and serum proteins in patients with aggressive periodontitis / 北京大学学报(医学版)

Objective:To investigate the potential association between FADS1 rs1 74537 polymorphism and serum proteins in patients with aggressive periodontitis,which may provide benefits for diagnosis and treatment of aggressive periodontitis.Methods:A total of 353 patients with aggressive periodontitis (group AgP)and 1 25 matched controls (group HP)were recruited in the study.Genotyping of FADS1 rs1 74537 and serum biochemical indexes were tested at the study’s start.The relationships between the levels of TP,GLB,ALB,A/G and genotyping were analyzed.Results:(1 )The detection rate of allele G in group AgP was higher than that in group HP(68.1% vs.61 .2%,P=0.046,OR=1 .35,95% CI 1 .00-1 .83 );the detection rate of genotype GG in group AgP was higher than in group HP(45 .5%vs. 34.4%,P=0.029,OR=1 .60,95%CI 1 .05 -2.44).(2)In group AgP,the patients with GG geno-type exhibited significantly lower TP,GLB than the patients with GT+TT genotype [(77.08 ±7.88)g/L vs.(79.00 ±4.66)g/L,P=0.007;(28.1 7 ±7.63)g/L vs.(29.88 ±3.49)g/L,P=0.007)and the higher A/G(1 .72 ±0.22 vs.1 .67 ±0.22,P=0.040),but there was no significant difference in ALB between the patients with GG genotype and the patients with GT+TT genotype.In group HP,there were no significant differences in TP,GLB,A/G and ALB between individuals with genotype GT+TT and with genotype GG.(3 )Compared with individuals with genotype GT+TT in group HP,the AgP pa-tients with genotype GT +TT exhibited significantly higher TP,GLB [(79.00 ±4.66 ) g/L vs. (75.20 ±4.53)g/L,P<0.01;(29.88 ±3.49)g/L vs.(26.55 ±2.94)g/L,P<0.01 )and the lo-wer A/G(1 .67 ±0.22 vs.1 .88 ±0.30,P<0.01 ),but there was no significant difference in ALB. There were no significant differences in TP,GLB,A/G and ALB the between the AgP patients with ge-notype GG and the healthy subjects with the same genotype either.Conclusion:FADS1 rs1 74537 poly-morphism is associated with aggressive periodontitis.The patients with genotype GG in group AgP had relatively lower TP,GLB and higher A/G.Genotype GG might be a risk indicator for aggressive periodon-titis by reducing host defense capability and contributing to inflammatory response in the occurrence and development of aggressive periodontitis.

Fatty Acid Composition of Tissue Cultured Breast Carcinoma and the Effect of Stearoyl-CoA Desaturase 1 Inhibition / 한국유방암학회지

PURPOSE: Stearoyl-CoA desaturase 1 (SCD1) is a novel therapeutic target in various malignancies, including breast cancer. The present study was designed to investigate the effect of the pharmacologic inhibition of SCD1 on fatty acid composition in tissue explant cultures of human breast cancer and to compare these effects with those in adjacent nonneoplastic breast tissue. METHODS: Paired samples of tumor and adjacent noncancerous tissue were isolated from 12 patients with infiltrating ductal breast cancer. Samples were explant cultured in vitro, exposed to the highly selective SCD1 inhibitor CAY10566, and examined for fatty acid composition by gas liquid chromatography. The cytotoxic and antigrowth effects were evaluated by quantification of lactate dehydrogenase release and by sulforhodamine B (SRB) measurement, respectively. RESULTS: Breast cancer tissue samples were found to have higher levels of monounsaturated fatty acids (MUFA) (p<0.001) and arachidonic acid (20:4n-6, p<0.001) and a lower level of linoleic acid (18:2n-6, p=0.02) than the normal-appearing breast tissues. While exhibiting no evident cytotoxicity, treatment with the SCD1 inhibitor, CAY10566 (0.1-1 microM), for 48 hours significantly increased 18:2n-6 levels in both the tumor and adjacent normal-appearing tissue (approximately 1.2 fold, p<0.05). However, the breast cancer tissue samples showed significant increases in the levels of MUFA and 20:4n-6 compared to the normal-appearing breast tissues (p<0.05). The SRB growth assay revealed a higher rate of inhibition with the SCD1 inhibitor in breast cancer tissues than in normal-appearing tissues (p<0.01, 41% vs. 29%). The SCD1 inhibitor also elevated saturated fatty acid (1.46-fold, p=0.001) levels only in the tumor tissue explant. CONCLUSION: The fatty acid composition and response to SCD1 inhibition differed between the explant cultures from breast cancer and the adjacent normal-appearing tissue. Altered fatty acid composition induced by SCD1 inhibition may also, in addition to Delta9 desaturation, modulate other reactions in de novo fatty acid synthesis and lipogenesis, and subsequently affect the overall survival and progression of breast cancer.

Mecanismos moleculares de acción de los ácidos grasos poliinsaturados y sus beneficios en la salud / Molecular mechanisms of action and health benefits of polyunsaturated fatty acids

Essential polyunsaturated fatty acids (PUFAs), linoleic acid n6 (LA) and linolenic acid (ALA) n3 obtained from the diet are precursors of the long-chain polyunsaturated fatty acids (Lc-PUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA) respectively. Consumption of PUFAs is related with a better neurological and cognitive development in newborns. It has been demonstrated that consumption of n-6 and n-3 PUFAs decreases blood triglycerides by increasing fatty acid oxidation through activation of PPARα or by reducing the activation of SREBP-1 inhibiting lipogenesis. Dietary PUFAs activate PPARα and PPARγ increasing lipid oxidation, and decreasing insulin resistance leading in a reduction of hepatic steatosis. Beneficial effects of PUFAs have been observed in humans and in animals models of diabetes, obesity, cancer, and cardiovascular diseases. It is important to promote the consumption of PUFAs. Main food sources of PUFAs n-6 are corn, soy and safflower oil, and for PUFAs n-3 are fish, soy, canola oil and, flaxseed. Finally FAO/WHO recommends an optimal daily intake of n6/n3 of 5-10:1.

Los ácidos grasos poliinsaturados indispensables (AGPIs), ácido linoleico n-6 y ácido linolénico n-3 se obtienen a través de la dieta y son precursores de los ácidos grasos poliinsaturados de cadena larga (AGPIs-CL) araquidónico (AA) y docosahexaenoico (ADH), respectivamente. El consumo de AGPIs está relacionado con un mejor desarrollo cerebral fetal y cognoscitivo del recién nacido. Los AGPIs pueden reducir la concentración de triacilgliceroles en la sangre a través de la oxidación de ácidos grasos por medio de la activación de PPARα o a través de la represión de SREBP-1 que inhibe la lipogénesis. El consumo de AGPIs puede ser benéfico en el control de ciertas enfermedades como la diabetes mellitus y la obesidad en la que los AGPIs activan a PPARα estimulando la oxidación de lípidos y disminuyendo la resistencia a la insulina y la esteatosis hepática. En el caso del cáncer los AGPIs pueden servir como agentes citotóxicos para ciertas células tumorales. Debido a su efecto hipolipémico y a su efecto antiinflamatorio, los AGPIs podrían tener efectos benéficos en la prevención de enfermedades cardiovasculares. Las principales fuentes alimenticias de AGPIs n-6 son los aceites de maíz, de cártamo y de soya, y las de AGPIs n-3 son la linaza y los aceites de pescados, canola y de soya. Finalmente, la FAO/ OMS recomienda un consumo óptimo de AGPIs diario en una proporción n-6: n-3 de 5-10: 1/día.